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Alnylam Pharmaceuticals Inc (NASDAQ:ALNY)
Q2 2020 Earnings Call
Aug 7, 2020, 8:30 p.m. ET

Contents:

  • Prepared Remarks
  • Questions and Answers
  • Call Participants

Prepared Remarks:

Operator

Ladies and gentlemen, thank you for standing by. Welcome to the Alnylam Pharmaceuticals Conference Call Second Quarter 2020. [Operator Instructions]

I would now like to turn the call over to the company. Please go ahead.

Christine Regan Lindenboom -- Investors and Media

Good morning. I'm Christine Lindenboom, Senior Vice President of Investor Relations and Corporate Communications at Alnylam. With me today on the phone are John Maraganore, Chief Executive Officer; Barry Greene, President; Akshay Vaishnaw, President of R&D Jeff Poulton, Chief Financial Officer; and Yvonne Greenstreet, Chief Operating Officer. Andy Orth, Head of the U.S. Business, is also on the phone and available for Q&A. For those of you participating via conference call, the accompanying slides can be accessed by going to the Events section of the Investors page of our website, investors.alnylam.com/events. During today's call as outlined in slide two, John will provide some introductory remarks and general context, Barry will provide an update on our commercial and medical affairs progress, Akshay will review recent clinical and preclinical updates, Jeff will review our financials and Yvonne will provide a brief summary of upcoming milestones before opening the call for your questions.

I would like to remind you that this call will contain remarks concerning Alnylam's future expectations, plans and prospects, which constitute forward-looking statements for the purpose of the safe harbor provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our most recent quarterly report on file with the SEC. In addition, any forward-looking statements represent our view only as of the date of this recording. It should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update such statements.

With that, I'd like to turn the call over to John.

John M. Maraganore -- Chief Executive Officer

Thanks, Christine, and thank you, everyone, for joining the call today. Let me start by expressing Alnylam's support for Black Lives Matter and our support for the efforts to end systemic racism in our country. At Alnylam, we stand against all forms of discrimination; and in our core, we believe, in justice, equity and inclusion. We stand in support of peaceful protest aimed at achieving real and sustainable change. Enough is enough, and it's time to finally cure the refractory scourge of hate. I'd also like to comment briefly on the Trump administration's recent announcement on drug prices. While we fully support the need to reduce or even eliminate patient out-of-pocket costs for prescription drugs, the administration's proposal to potentially introduce a so-called Most Favored Nation executive order is both unfortunate and misguided. Importing foreign price controls will harm American innovation and hurt our patients. Even if this executive order is finalized, we don't believe it will stand. With that, let's now turn to our business. As all of you know, the COVID-19 pandemic remains dynamic, uncertain and unpredictable. That said, we continue to view the situation in the same framework we discussed last quarter: a pandemic phase in Q2, a recovery phase in Q3 and a new normal starting in Q4. While the pandemic continues or even worsens in many states in the U.S., we believe Alnylam's business is benefiting from our broad global presence. In spite of the ebbs and flows, we are seeing healthcare systems now remaining open, and we don't currently expect a repeat shutdown of healthcare systems like what was seen in Q2, especially in the April-May time frame. Our confidence in the second half is reflected in an upward revision in our ONPATTRO revenue guidance range.

Overall, we're really proud of our field teams around the world and their ability to adapt quickly and safely to meet the needs of patients, embodying our challenge accepted mentality. We are extremely pleased with global ONPATTRO and GIVLAARI top line performance in Q2, which Barry will elaborate on shortly. We're also proud of the significant progress we made across our pipeline in the quarter, as Akshay will discuss. Another highlight for the quarter was our landmark strategic financing collaboration and inclisiran royalty monetization we completed with Blackstone Life Sciences worth up to $2 billion. We believe this collaboration secures our bridge toward a self-sustainable financial profile without the need for any future equity financings. Now before I share my before I close before I share my closing remarks, I want to take a moment to acknowledge the news we announced earlier this morning about Barry Greene's planned departure from Alnylam at the end of the quarter. Barry and I have been working side by side for over 20 years, first at Millennium and then for 17 years at Alnylam. And I know that I speak for everyone at Alnylam in thanking Barry for his exceptional contributions and dedication to the company. We all owe him tremendous gratitude for his outstanding leadership and track record that have contributed to the delivery of RNAi therapeutics as a whole new class of medicines for patients. I have no doubt Barry will continue to be a highly impactful leader in the life sciences. I'm grateful for his agreement to consult with Alnylam as needed for a two-year period, and I wish him all the very best in his next endeavors.

We are also very pleased to share that Yvonne Greenstreet, our current Chief Operating Officer, will step into the expanded role of President and Chief Operating Officer on October 1. We believe Yvonne is uniquely suited for this opportunity given her strong command of our business, strategic leadership and proven ability to drive results. We are initiating a search for a Chief Commercial Officer. And during the search, we anticipate no impact to our ongoing commercial execution. Please join me in wishing Barry well as he pursues the next chapter of a remarkable career and congratulating Yvonne on her expanded role at Alnylam. I'd like to finish with my perspective on the big picture for the company. We continue to lead the advancement of RNAi therapeutics as a whole new class of medicines, and we remain on track to achieve and exceed our Alnylam 2020 goals, exiting 2020 as a multiproduct global commercial company with a deep clinical pipeline for future growth and a robust and organic product engine for sustainable innovation. Without a doubt, we're excited for the promising future that Alnylam is poised to deliver as a top-tier biopharmaceutical company focused on advancing medicines with transformative potential for patients around the world.

With that, I will now turn the call over to Barry for one last time, Barry, to review our commercial progress and medical affairs activities in more detail. Barry, take it away.

Barry Greene -- President

Thanks, John, and good morning, everyone. Before I provide the quarterly highlights, I'd like to make some brief remarks about my planned transition from Alnylam. First, congratulations again to Yvonne Greenstreet. She is a remarkable person and well deserves the President and COO role. I know that Yvonne will make sure that Alnylam continues to be a company doing the right things and focusing on patients, and I'm counting on it. As for me, it's been a tremendous privilege to serve as President of Alnylam for such a long period of time. I'm very proud of what we've been able to accomplish during my 17 years, and we built a global fully integrated multiproduct company that is recognized for excellence in R&D and recently for our commercial strength as well. My decision to transition is based on the desire to pursue new leadership opportunity in the next chapter of my career. I'm fully confident Alnylam will achieve its ambitious goals with quality and excellence with the great team we have in place. I'll continue to support Alnylam throughout this transition and have no doubt about the company's future prospects as a top-tier biopharmaceutical company. So let's now review our. For ONPATTRO, we achieved $66.5 million in global net product revenues. As of June 30, over 1,050 patients were on commercial ONPATTRO treatment worldwide, representing an increase of over 100 patients from end of Q1, a very impressive accomplishment in the height of the global pandemic during Q2.

Let's start with some more color on the U.S. As anticipated, the COVID-19 pandemic had impact on our business in the second quarter, with patient demand decreasing due to reduced adherence as some patients skip doses or experience dose delays while moving to new care sites. Also as anticipated, we saw the pace of new patient initiating therapy slow in the U.s. during the quarter due to reduced genetic testing, diagnosis and patient flow through the healthcare systems. Finally, our U.S. business was also impacted by inventory destocking and an increase in cost in the second quarter. Jeff will provide more color on these details later in the call. While our focus today is on Q2, as we enter Q3, we're now seeing what looks like a healthy return of genetic testing and patient flow through the U.S. healthcare system even in states where COVID-19 cases are rising. And in fact, our July, on our last numbers are near the January numbers we saw earlier in the year. A really good sign. In the second quarter, we continue to see great progress in new prescribers. For the second quarter, 40% of submitted start forms came from new writers with an equal mix of neurologists and cardiologists. In the U.S., we saw continued concomitant use of ONPATTRO with TTR stabilizers in the quarter. We believe this trend will continue to grow as physicians see progression of polyneuropathy on stabilizers and treat the different manifestations of hATTR amyloidosis. Now turning to the rest of the world. We made very positive progress with ONPATTRO in the second quarter. Rest of world sales for ONPATTRO were $34.2 million and relative to the U.S. benefited from continued geographic expansions with launches in Spain, Italy and other countries. In addition, we saw relative strength in our ex U.S. markets between Europe and Japan for their management of the pandemic. As John noted, this is a nice validation of the decision to build a global, fully integrated business. With today's announcement of achieving pricing and reimbursement agreement in France, we're pleased to report that access has been secured in all priority markets in Western Europe. Notably, our team has secured pricing and reimbursement approval in all major European markets in under two years post-approval by the EMA. This is a much faster rate than most orphan medicines are able to achieve. Japan was again a country of strength for ONPATTRO. Japan has now become our second-largest country after the U.S. for our ONPATTRO revenue, and we expect continued growth in new patient discussion on stabilizer therapy.

On the medical care side, our team remains committed to addressing the challenge of raising disease awareness and improving diagnosis of hATTR amyloidosis, including with Alnylam Act, our third-party genetic screening initiative in the U.S., Canada and Brazil. As of July, over 27,000 samples have been submitted, out of which over 1,600 have tested positive for pathogenic TTR mutation, which is tracking at a historic 6% to 8% positivity rate. These numbers show the testing slowdown in Q2 we mentioned on our last earnings call. The good news is that, those numbers have picked up to near January levels. Moving on to GIVLAARI. We are really pleased with the progress in our launch, most of which was done virtually. We achieved $11 million in global net product revenues. We received over 85 start forms in the U.S. with over 100 patients globally on commercial treatment from launch through June 30. As we have now begun to open ex U.S. territories and also because currently 25% to 30% of U.S. patients come from outside the start form channel, we'll discontinue providing start form metrics in future quarters as we did last year for ONPATTRO. In the U.S., we observed a broad prescriber mix, including hepatologists, gastroenterologists and other specialties, both in preferred centers of excellence and in the community. Of note, 76% of our Q2 starts were from new writers. Our progress with value-based agreements has been extremely strong with seven VBAs completed with U.S. payers, and we now have confirmed access for over 75% of covered U.S. lives across commercial, Medicaid and other government payers. We've not experienced any care to date, pleased to see plans adopt medical policies, not more restrictive than our labeled indication. ASMR III saw strong initial performance as well with the successful and as noted virtual launch in Germany as well as named patient sales in other countries, including French cohort ATU program. We've been positively encouraged by the responsiveness of European payers despite the COVID-19 pandemic. Of note, GIVLAARI received an improvement of medical benefit or ASMR score of two in France, concluding that GIVLAARI offers significant additional therapeutic value. This is an enormous accomplishment. For context, only two new commercial medicines were granted with an ASMR rating of two for 2019.

Our medical affairs team is also focused on improving awareness and diagnosis with AHP. Through Alnylam Act, we can report 937 test submitted and 92 patients with positive AHP mutations as of mid-July, showing continued 10% positivity rate. A notable diagnosis trend emerging is the robust use of urinary PPG test informed diagnosis, and we expect patient identification efforts will be meaningfully enhanced by this nongenetic testing method. Of course, we're now also preparing for the potential launch of lumasiran later this year. Importantly, we'll be leveraging our existing commercial infrastructure for this launch with small additions of resources for field-based teams. When we gain approval, we'll let specific commercialization support medicine therapeutic expected to market. In conclusion, the second quarter was challenging due to the pandemic particularly in the United States, but was much better than the downside case we anticipated as we entered Q2. The credit goes to our teams around the world who face the obstacles head on to deliver the important medicines to our patients.

With that, I'll now turn the call over to Akshay to review our recent R&D and pipeline progress. Akshay?

Akshay Vaishnaw -- President, Research and Development

Good morning, everyone, and thank you, Barry. I should say thank you, Barry, for guiding me, for helping build our company and, most of all, for working so tirelessly to help all the patients we seek to serve. So with that, I'll start with our efforts in ATTR amyloidosis where we're advancing our two product candidates: patisiran and vutrisiran. As ONPATTRO is currently approved in multiple markets around the world to treat polyneuropathy associated with hATTR amyloidosis, we're committed to expanding the product's label to include the treatment of cardiomyopathy in both hereditary and wild-type ATTR amyloidosis patients. To this end, we continue to enroll patients in APOLLO-B and continue to expect completion of enrollment in 2021. We've seen enrollment pick up over the last month as clinical sites start to open up around the world. In addition, we're also advancing vutrisiran, an investigational RNAi therapeutic delivered by quarterly subcutaneous injection that's also in development for the treatment of ATTR amyloidosis. Here, we're conducting two Phase III studies. The first is HELIOS-A, which is evaluating vutrisiran in hATTR amyloidosis patients with polyneuropathy. Enrollment is complete in HELIOS-A, and we remain on track to report top line results early next year. The second Phase III study of vutrisiran is HELIOS-B, which is being conducted in in inherited and wild-type ATTR amyloidosis patients with cardiomyopathy. As with APOLLO-B, site activation enrollment in HELIOS-B are now picking up. If HELIOS-B is positive, it could allow for vutrisiran's entry into the very large wild-type ATTR amyloidosis market opportunity with the product label that includes cardiovascular outcomes.

Let's move to GIVLAARI, which is approved in the U.S., EU and now in Brazil to treat acute hepatic porphyria in adults. Of course, the highlight of GIVLAARI in the recent period was our Brazilian approval, and we're continuing our geographic expansion for this product with MAA submitted in Switzerland and Israel and plans for submission in Japan in the coming months. During the second quarter, we also presented a new 12-month interim data from the ENVISION Phase III study, demonstrating sustained efficacy and acceptable safety through 12 months of treatment, with evidence for potentially improved efficacy over time. In addition, we're proud to have published pivotal results from the ENVISION Phase III study in The New England Journal of Medicine. This is our ninth paper on RNAi therapeutics published in the journal. I'll now turn to recent progress with lumasiran, an investigational RNAi therapeutic that we're developing for the treatment of primary hyperoxaluria type 1, or PH1. At the ERA-EDTA meeting in June, we reported the full set of positive results from ILLUMINATE-A, which demonstrated that lumasiran significantly reduced urinary oxalate levels, the cause of progressive kidney failure in PH1. In addition, lumasiran showed an encouraging safety profile. Our overall lumasiran program also includes our ILLUMINATE-B study in pediatric patients under six years of age. Enrollment is complete, and we remain on track to report top line results soon in mid-2020. The ILLUMINATE-C study in severe PH1 continues to enroll and has been proceeding well even during the pandemic. We completed our NDA and MAA submissions in the second quarter. The FDA granted priority review for the NDA and has set an action date of December 3, 2020. EMA has granted accelerated assessment of the MAA. As you know, we have two additional late-stage programs that are in development with partners. This includes inclisiran in the development in development for hypercholesterolemia partnered with Novartis, which is currently under review for approval in the U.S. and EU. Both NDA and MAA filings have been accepted, and Novartis expects initial approval in the U.S. in late 2020. Novartis has indicated that they remain on track for approval this year with a December action date in the U.S.

Our late-stage pipeline also includes fitusiran in development for hemophilia A or B with or without inhibitors, partnered with Sanofi. Sanofi has recently disclosed that two of the three ATLAS Phase III studies have completed enrollment and that they remain on track to report top line ATLAS Phase III data in the first half of 2021. Sanofi also presented new positive results from an interim analysis of the Phase II OLE study of fitusiran, showing impressive reductions in the annualized bleeding rate with encouraging safety. Now in addition to our late-stage clinical programs, we believe we've also been making great progress with our early and mid-stage programs. The highlights of the quarter was the positive top line results from our ALN-AGT Phase I study in patients with hypertension, specifically ALN-AGT demonstrated an over 90% knockdown of angiotensinogen and a greater than 10 millimeters mercury lowering systolic blood pressure with the durability that's caused a quarterly or even less frequent subcutaneous dosing regimen. We're also encouraged by the tolerability profile for ALN-AGT. We now look forward to presenting more complete data from the ongoing Phase I study at a scientific meeting in the second half, assuming abstract acceptance. We're very excited about the potential for ALN-AGT to reimagine the treatment of hypertension with tonic-controlled blood pressure that we believe could result in important benefit for patients. Our next clinical program is ALN-HSD, an investigational RNAi therapeutic for the treatment of NASH, for which we recently filed a CTA. This program is being advanced in collaboration with Regeneron. We're also making strong progress on our many RNAi therapeutic opportunities beyond the liver. For our COVID-19 RNAi therapeutic collaboration with Vir, we selected a development candidate, ALN-COV or VIR-2703, with potent and highly cross-reactive activity toward SARS-CoV-2, the virus that causes COVID-19. We continue to expect an IND filing around year-end 2020. We're also pleased to announce today that Regeneron has elected to opt-in to the ALN-APP program. We aim to get an IND filed for ALN-APP in mid-2021, and this is expected to be our first CNS program to enter clinical development.

And with that, let me now turn it over to Jeff to review our financial results. Jeff?

Jeff Poulton -- Chief Financial Officer

Thanks, Akshay, and good morning, everyone. I'm pleased to be presenting Alnylam's Q2 2020 results. As Barry has already highlighted, it was a very strong quarter of commercial execution, with outstanding results for both ONPATTRO and GIVLAARI. Turning to our results first for ONPATTRO, generated $66.5 million in global net ONPATTRO revenue for the quarter, which was impacted by the pandemic, particularly in the U.S., with global growth being flat versus the first quarter of 2020 and a 74% increase compared with Q2 2019. U.S. growth decreased 13% during the quarter compared with Q1 and was primarily impacted by the following: a 4% decrease in demand from reduced patient adherence due to the COVID-19 pandemic, as Barry previously mentioned; an 8% reduction due to inventory destocking during the quarter with pending inventory now at 1.5 weeks in the distribution channel at the end of Q2; and a 1% decrease due to a modest increase in gross to net deductions in the quarter. We continue to expect gross to net deductions will remain in the mid-20s globally for ONPATTRO in 2020. In our international markets, performance was very strong in spite of the pandemic, with growth of 16% versus Q1. Growth in Europe was highlighted by strength in recently launched markets in Italy and Spain. While in Asia, growth in Japan remains robust, with Japan now representing our second-largest market for ONPATTRO based on dollar sales, as Barry mentioned. First time this quarter, the contribution of our international markets to global ONPATTRO sales exceeded the U.S. contribution. We are pleased to have a strong and global brand, which we believe is beneficial to long-term growth. Turning to our results for GIVLAARI. We had a strong second quarter, generating $11 million in global net revenue in the quarter, representing over 100% growth compared to the first quarter.

This growth was driven by ongoing success of the U.S. launch where we did not experience reductions in patient adherence at the same level as ONPATTRO as well as an additional contribution from our international markets with a successful launch in Germany and named patient sales in other countries, including France. Our combined product sales for ONPATTRO and GIVLAARI were $77.5 million for the quarter, representing 6% growth versus Q1, a strong result given the challenges associated with COVID-19 in the quarter. Turning now to a summary of our full P&L results for the quarter. Net revenue from collaborations for the second quarter was $26.4 million, a significant increase from last year primarily due to revenue recognized from our Regeneron and Vir collaborations. Gross margin as a percentage of total revenue was 81% for the quarter, down from 90% in Q2 2019 primarily due to the current utilization of ONPATTRO full cost inventory. Last year benefited from 0 cost ONPATTRO inventory as well as having a higher proportion of sales in the second quarter of 2020 coming from lower-margin international markets and a write-off of ONPATTRO inventory at our contract manufacturer. Our R&D expenses decreased on a non-GAAP basis in the second quarter of 2020 compared to the same period in the prior year primarily due to nonrecurring expenses in 2019 from license fees related to the execution of our collaboration agreement with Regeneron as well as a decrease in expenses associated with material manufactured for clinical trials. Conversely, SG&A expenses increased modestly on a non-GAAP basis in the second quarter of 2020 compared to the same period in the prior year primarily due to increased investment in commercial and medical affairs activity to support the ongoing launches of ONPATTRO and GIVLAARI and initial launch preparation activities for lumasiran. Importantly, our non-GAAP operating loss for the second quarter decreased by approximately $40 million compared with the same period in 2019 driven by a combination of strong top line growth and very moderate growth in operating expenses. We remain confident that 2019 represents our peak non-GAAP operating loss year as we expect the trend of strong top line growth and moderate growth in operating expenses will continue for the balance of the year. We ended the quarter with cash and investments of $1.95 billion, which includes $600 million in proceeds received in the second quarter from the partial sale of future inclisiran royalties and issuance of common stock to Blackstone.

Finally, turning to our financial guidance. We believe our results for the second quarter demonstrate the strength of our commercial teams in challenging circumstances. As a result of the strong commercial performance for ONPATTRO that exceeded our initial expectations back in the earlier phase of the pandemic in May, we are further revising our full year revenue guidance for ONPATTRO, with an increase in the midpoint of our guidance as we narrow the range from $270 million to $300 million to $280 million to $300 million. Guidance range for combined non-GAAP R&D and SG&A expenses as well as our guidance for net revenue from collaborations remain unchanged. Please note that we have revised the midpoint of our GAAP combined R&D and SG&A operating expense guidance downward by $25 million, reflecting a reduction in expected stock-based compensation during the year. Regarding cash, we believe our strategic financing collaboration with Blackstone, adding up to $2 billion in cash, secures Alnylam's bridge toward a self-sustainable financial profile without the need for future equity financings.

And with that, I'll now turn the call over to Yvonne to review our goals for the remainder of the year. Yvonne? Thanks, Jeff, and hello, everyone. Looking ahead to the second half of 2020, we have a number of important milestones lined up. Of course, we plan to continue our global commercialization of both ONPATTRO and GIVLAARI, and we're looking forward to our GIVLAARI launch in Brazil and an upcoming NDA filing for GIVLAARI in Japan. We're also expecting two additional regulatory approvals by the end of the year for lumasiran and inclisiran. We plan to continue enrollment in our ATTR cardiomyopathy studies, specifically APOLLO-B with patisiran and HELIOS-B with vutrisiran. With lumasiran, we're on track to share top line results of the ILLUMINATE-B Phase III study in mid-2020. And of course, we'll also continue advancing the rest of our pipeline as well as exciting preclinical efforts, and we'll highlight these milestones throughout the year as they occur. Among these will be our presentation of additional clinical results from the ongoing Phase I trial of ALN-AGT in hypertension program we're very excited about. We also plan to initiate a Phase I trial of ALN-HSD for NASH, having now filed the CTA for that program. And our partner, Regeneron, plans to initiate a Phase I study of cemdisiran in combination with pozelimab, having now filed the CTA for that study. We also hope that you'll join us for our remaining RNAi roundtables focused on lumasiran, givosiran and our TTR programs later in August and September. Let me now turn it back to Christine to coordinate our Q&A session. Christine?

Christine Regan Lindenboom -- Investors and Media

Thank you, Yvonne. I just wanted to quickly acknowledge, we found issue with Barry's prepared remarks. There are some storms that are rolling through his area that impacted the audio quality, and we will plan to have Barry rerecord his remarks for the replay of this call.

So operator, let's now open the call for questions. [Operator Instructions]

Questions and Answers:

Operator

[Operator Instructions] We will now take our first question from Paul Matteis from Stifel. Please go ahead. Your line is open.

Paul Matteis -- Stifel Nicolaus -- Analyst

Great. Thanks so much. And congrats, Barry. You're definitely going to be missed. And Yvonne, congratulations to you as well. I guess just a couple of quick commercial things. So on the dynamics that impacted ONPATTRO this quarter, you grew patients on drug, but revenues were down. As you think about inventory, net price, as you expand globally in compliance in the second half given the pandemic, can you just help us understand how these variables are looking maybe in July and what you expect later this year? And then just on the commercial transition, it would be helpful if you could comment on your confidence that this won't disrupt the GIVLAARI launch. This is obviously a launch that requires a lot of blocking and tackling and finding patients, and you're really in the midst of a ramp-up. So how do you kind of manage the transition in the midst of that?

John M. Maraganore -- Chief Executive Officer

Yes. Paul, thanks. Great question. So on ONPATTRO, let's start, Jeff, with you. And then maybe, Andy Orth, you can comment as well on some of the emerging Q3 dynamics and our confidence there. So Jeff, do you want to start?

Jeff Poulton -- Chief Financial Officer

Yes. Sure. I think that Barry made a couple of comments in his prepared remarks that we did start to see some encouraging signs toward the end of the second quarter and into the third quarter, notably on genetic testing, Alnylam Act. We saw recovery rates that were close to what they were prior to the pandemic setting. And I think we're also seeing improvements in adherence, which was the major headwind that we saw in the earlier part of the quarter in the U.S. And then lastly, I think there was a question about stocking in there. We're at the lower end of the range. So our distribution partners contractually hold between one and three weeks, and we're at 1.5 weeks right now. So there could be some additional build in the second half of the year.

John M. Maraganore -- Chief Executive Officer

Great. And Andy, do you want to comment a little bit further on the dynamics here as we enter the third quarter?

Andy Orth -- Senior Vice President, Head of the U.S. Region

Sure, sure. And Paul, as you mentioned here, even amid the healthcare shutdown in the U.S., we were able to increase the net patients on ONPATTRO. It was the adherence, which was the main driver of the demand impact, as Jeff just mentioned as well. And in June and July, we have seen dramatic progress in both the resumption of patient flows through the healthcare system and Alnylam Act volumes and other things we metric as well as the adherence rate improving across all the sites of care.

John M. Maraganore -- Chief Executive Officer

Yes. And I would just add on ONPATTRO that, for example, Paul, PYP scans is an important way that patients get diagnosed with this disease. And if they have polyneuropathy, then they become appropriate patients for ONPATTRO. And our July PYP scans were comparable to what we saw in January. For example, this is things that we can track across the country. So that's a good sign. Now let's turn to the GIVLAARI question. Barry, do you want to comment a little bit on the GIVLAARI question in terms of our confidence in the second half of the launch given the ebbs and flows of the pandemic?

Barry Greene -- President

Absolutely. Is my audio better? The storm has passed.

John M. Maraganore -- Chief Executive Officer

It is much better.

Barry Greene -- President

As I was speaking, my lights literally went out as I opened my starting remarks. So I apologize for the muffling. Yes. So Paul, great question on GIVLAARI. I'll remind you that in these kinds of rare diseases where diagnosis rates are very low because physicians aren't really looking, patients come from three different buckets. They come from patients transitioning from EAP, patients known to the sites and then brand-new, newly diagnosed patients. And as we mentioned, at the beginning with the pandemic, we were highly prepared with digitization and virtualization already for GIVLAARI given the diverse prescriber base and the fact that patients can be anywhere in the world. So we, in fact, have done virtual launches, and they've done very well and have not been really detriment, as we've seen based upon results, to our success in getting to healthcare providers and educating them, reaching out to patient advocacy groups and ensuring that patients who are prescribed get access to the payers.

So all three have been going very well. I guess the other comment I'll have is the fact that the healthcare providers now due to the COVID situation are also being forced to get online has actually aided the strategy we've had for digital and virtual interactions because now they're more used to it, they're willing to do it and we've had really remarkable ad coms and speaker programs with numbers that you've never seen before when they were local and live. So while nothing is good as in person, we've really taken advantage to help patients as best we can during this time.

John M. Maraganore -- Chief Executive Officer

And I'll just add one last point on GIVLAARI, which is that we do benefit from a drug that's been proven in clinical studies to decrease hospitalizations related to the annualized attack rate reductions that we see, and that obviously is good in this current circumstance. So Paul, does that answer your questions?

Paul Matteis -- Stifel Nicolaus -- Analyst

Absolutely. Yes it does. Thanks so much for the added color. I appreciate it.

John M. Maraganore -- Chief Executive Officer

Thank you.

Operator

We will now take our next question from Alethia Young from Cantor. Please go ahead. Your line is open.

Alethia Young -- Cantor Fitzgerald -- Analyst

Hey guys, thanks for taking my question and Congrats, Barry. You deserve it. And Yvonne, we look forward to working with you further. Always a pleasure. So I just wanted to ask a little bit about, kind of a little bit off kilter here, how you're thinking about kind of the hemophilia landscape in fitusiran and how that's positioned in light of what's going on with gene therapy. I know it's a Sanofi product, but I just want to kind of get your perspective on that since we are getting relatively close to data.

John M. Maraganore -- Chief Executive Officer

Yes. Absolutely. Let me make some comments, and then I welcome Akshay's perspectives as well. Obviously, the hemophilia market is a multi-product, multi-company market. There are many players already. There are dozens of over a dozen products that are available for patients with hemophilia A or B with and without inhibitors, which is great. Fitusiran really fits in as the only once-monthly subcutaneous medicine that shows ABR levels, annualized bleeding levels, that are around 1. And that really is a unique positioning for the product in our view, in Sanofi's view. And so if that holds up in the Phase III trials and the safety continues to hold up as was encouragingly shown in their updated open-label study, this could be a very important medicine in that landscape and offer competitive profile compared to Hemlibra as the potentially only really effective once-monthly subcutaneous medicine. Akshay, do you want to comment any further on that?

Akshay Vaishnaw -- President, Research and Development

Yes. It's a very interesting and dynamic time in the hemophilia landscape, Hemlibra, the gene therapies. I think at premium, with all of these approaches, of course, is safety. This is a very delicate population where there have been significant safety events in the past. But I think both with Hemlibra and gene therapy, this will continue to be a discussion. Obviously, they've completed their Phase III studies and the primary in Phase III study with the hemophilia A therapy. But durability of effect with gene therapy, the long-term safety, including the potential for oncogenesis, this remains a question in our opinion. There have been recent dog studies that showed that very late long-term cancer events can occur with gene therapy for hemophilia. But look, it's a good time for patients to have more therapies come on. As John said, a therapy for hemophilia A and B that's convenient and safe once-a-month subcu would obviously be very attractive. And we think fitusiran can offer that both for on-demand prophylaxis and inhibitor patients and even beyond that in the other bleeding disorders. So this a unique and differentiated offering, and we eagerly await Phase III data.

John M. Maraganore -- Chief Executive Officer

Yes. Early next year, as you said, Alethia, which is exciting. Does that answer your question?

Alethia Young -- Cantor Fitzgerald -- Analyst

Yes. Very helpful. Thank you, guys.

John M. Maraganore -- Chief Executive Officer

Alright. Thank you.

Operator

We will now move to our next question from Anupam Rama from JPMorgan. Please go ahead. Your line is open.

Anupam Rama -- JPMorgan -- Analyst

Hey, guys. Thanks so much for taking the question. And for APOLLO-B, post the primary endpoint analysis, there's a 12-month extension in the trial. Will you be continuing that on a blinded basis so that you'll be able to get sort of outcome data in a placebo-controlled manner? Or will you really be relying on patisiran to get some of those longer-term outcomes beyond 12 months? And for Barry, always admired the hustle, man.

John M. Maraganore -- Chief Executive Officer

Yes. All right. So Akshay, I think the APOLLO-B question is right up your alley.

Akshay Vaishnaw -- President, Research and Development

Yes. The principal focus for APOLLO-B, as you said, Anupam, is on the 12-month analysis. And vutrisiran will be coming in close succession after that readout the 12-month readout for patisiran in APOLLO-B. And so, of course, that will form the principal demonstration of our TTR approaches and what they can do in terms of morbidity and mortality in the long term.

John M. Maraganore -- Chief Executive Officer

Yes. I'll just add. Obviously, we are capturing mortality at CV hospitalization data in APOLLO-B on a pub. So we'll obviously collect those data and see what they report. One year's worth of treatment is probably not and the power is not the study is not powered to show something there, but we'll certainly be collecting those data. And those types of data may inform how we think about the interim analysis for HELIOS-B, which is our vutrisiran study, and that's obviously going to be a nice, helpful set of data as we consider what that looks like.

Anupam Rama -- JPMorgan -- Analyst

Thanks for taking the question.

John M. Maraganore -- Chief Executive Officer

Thanks Anupam.

Operator

We will now take our next question from Tazeen Ahmad from Bank of America. Please go ahead. Your line is open.

Tazeen Ahmad -- Bank of America Securities -- Analyst

Hi, good morning, guys. Thanks for taking my questions. A quick one. As it relates to ONPATTRO sales. With ex U.S. now higher than the U.S., would you relate that, at least near term, as an impact from COVID? And do you expect that trend to continue for the duration that COVID is a meaningful factor at least here in the U.S.?

And then I do want to get your early thoughts about Regeneron opting in for your ALN-APP program, your plan on starting development of that program. Can you give us a little bit of color on what you think the opportunity could be in IgA nephropathy?

John M. Maraganore -- Chief Executive Officer

Okay. So let me start with the second half, which second part of the question, which I think was mixed two different programs in it, Tazeen. And then, Barry, you should answer the first question. Regarding APP, that's our amyloid precursor protein program that they opted into. And that's going to that's on track to have a filed IND or CTA in middle 2021. That will be our first CNS program. So they opted into that program. That's different than cemdisiran, which is our C5 program, which they already had opted into. That's part of our original agreement with them, which is currently in a Phase II study in IgA nephropathy. What they're also doing is they're doing combination studies with cemdisiran together with pozelimab, which is their anti-C5 antibody to get the benefit of an infrequent subcutaneously delivered treatment for many complement-mediated diseases like PNH and myasthenia, among others. So that's that part of the question, Tazeen. Barry, do you want to answer the first one on U.S., rest of world ONPATTRO and how that how we see that going forward?

Barry Greene -- President

Yes, absolutely. As Jeff provided on the call, we've upped our mid guidance, reflecting our belief set that we're in the recovery phase. So in particular, we believe that we're going to continue to see growth in the U.S. I'll remind you that as a mature market, the U.S. is really a pure patient-find market right now. And as patients are, again, flowing through the healthcare systems, we're finding the proportion of patients TTR that are hereditary with polyneuropathy. So we continue to see growth in the U.S. In terms of rest of world, many countries continue to benefit by patients known to site as well as finding new patients. And then we are opening new territories. So every time a country opens, we benefit by EAPs in those countries than patients known to site. So again, we see growth in all regions around the world continuing.

John M. Maraganore -- Chief Executive Officer

Yes. And Jeff, anything you'd want to add or Andy to that?

Jeff Poulton -- Chief Financial Officer

Nothing for me to add.

John M. Maraganore -- Chief Executive Officer

Andy?

Andy Orth -- Senior Vice President, Head of the U.S. Region

No. Agreed. I think Barry got it.

John M. Maraganore -- Chief Executive Officer

Great.

Yvonne Greenstreet -- Chief Operating Officer

I just have one thing to add. I think John, just one thing to add. It's Yvonne here. I think the increasing use of combination therapy in the U.S. is a dynamic that I think is a very interesting one for us. But I think we're beginning to see physicians appreciate the profile of ONPATTRO in this mixed population phenotype. So I think that's something to keep an eye on as well.

John M. Maraganore -- Chief Executive Officer

Yes, absolutely.

Tazeen Ahmad -- Bank of America Securities -- Analyst

And I did want to I'm sorry, I mangled my second question. I did want to ask why APP would start development ex U.S.?

John M. Maraganore -- Chief Executive Officer

Oh, there's no plan to do it ex U.S. necessarily, Tazeen. We often start studies in different parts of the world, including sometimes in the U.S. So there's no it's not a plan to do it ex U.S. per se.

Tazeen Ahmad -- Bank of America Securities -- Analyst

Okay.

John M. Maraganore -- Chief Executive Officer

Okay. Thank you.

Operator

We will now take our next question from Maury Raycroft from Jefferies. Please go ahead. Your line is open.

Maury Raycroft -- Jefferies -- Analyst

Hi everyone. Good morning and Congrats on the progress. First one is just on APOLLO-B. So we know from your exploratory endpoints in the Phase III APOLLO-A at ONPATTRO or patisiran showed activity in cardiomyopathy phenotypes. I'm wondering if you're collecting data from the commercial patients on ONPATTRO that provides read through to APOLLO-B. And will you present those data at some point? And can you comment on some key baseline factors with similarities between patients using the drug commercially versus those involved in APOLLO-B?

John M. Maraganore -- Chief Executive Officer

Yes. That's a great question. I'm going to maybe provide some context. Maybe, Akshay, you can comment as well and Barry. Look, we're obviously, in the original APOLLO study, APOLLO-A, as you said, there were very encouraging exploratory data generated in patients with cardiomyopathy prespecified cardiomyopathy that our hypothesis generating they formed the foundation of our confidence in APOLLO-B. And I think to your point, there's been some interesting data that have been generated investigationally in the field in patients that have polyneuropathy, but also with cardiomyopathy where patisiran is being used, specifically looking at cardiac amyloid imaging. And some of the data that have been in one case, published by a Dutch group and then the National Amyloidosis Centre in the U.K. has presented some data, are really quite encouraging and give us encouragement for APOLLO-B. Of course, we'll await the results of that study before we can comment definitively on patisiran's activity in cardiac patients. Akshay, anything to add to that from your perspective?

Akshay Vaishnaw -- President, Research and Development

No. I think you covered it, John.

John M. Maraganore -- Chief Executive Officer

Yes. Great. And I'll just add that there are always investigational studies that are done by individual centers or groups of physicians that might explore these type of features. And that's something which does occur out there. Barry, anything else to add on the commercial side?

Barry Greene -- President

No. I think you covered it well.

John M. Maraganore -- Chief Executive Officer

Perfect. Thank you. Maury, does that answer your question?

Maury Raycroft -- Jefferies -- Analyst

That does. That's very helpful. And just a quick follow-up for AGT. So in your top line data, you guys reported on 48 patients for that, and you're going to have additional data at the end of this year. I think you can enroll up to 184 for that study. Just wondering if you can comment more on how many patients you plan on enrolling? And I guess, how much total data could we see at the end of the year?

John M. Maraganore -- Chief Executive Officer

Yes. I mean we a lot of these Phase I studies are engineered with optional cohorts that allow us to add additional subjects patients, in this case, to the study design. I think it's still we still haven't decided at what point we will have completed that study. But we are still answering important questions, including potentially on combination with other antihypertensive meds to explore that in the study, both from an activity and safety perspective. Akshay, anything else to add to that?

Akshay Vaishnaw -- President, Research and Development

No. I think that you covered it. Yes.

John M. Maraganore -- Chief Executive Officer

Great. Does that help, Maury?

Maury Raycroft -- Jefferies -- Analyst

Yes that helps. Thanks for taking my questions.

John M. Maraganore -- Chief Executive Officer

Thanks Maury.

Operator

We will now move to our next question from Ritu Baral from Cowen. Please go ahead. Your line is open.

Ritu Baral -- Cowen -- Analyst

Hi, guys, thanks for taking the question. Barry, great to work with you over the years and best of luck. And Yvonne, really, just congratulations, looking forward to working with you more. I wanted to ask about trends in home administration for ONPATTRO. I guess is there any difference between what you're seeing in the U.S. and Europe? And what is being done in the U.S. as far as allowances for COVID and reimbursement and uptake? Is this something we could see that will be a lever going forward to stabilizing U.S.?

John M. Maraganore -- Chief Executive Officer

Yes. I mean it's a great question. Barry, do you want to give the global view? And then maybe, Andy, you can add additional color on the U.S. dynamics on that?

Barry Greene -- President

Absolutely, and great question. Home infusion has been a critical care site that we've utilized during the pandemic. So in the CEMEA region, home use was about 17% pre-pandemic, and it's doubled to about 35% in the age of pandemic in terms of dynamics. France, in fact, was able to move these cohort of patients into home infusion when one of the sites reported infectivity with COVID. So it's been very important. Andy can comment more, but the U.S. has also doubled from 9% to about 20%. And then globally, in countries that allow home infusion, u.S., Brazil, Canada and most of the European countries, we've effectively been able to move patients to home infusion. There are times where a dose is delayed or dose is skipped in that transition. But as we've now got the capability down, most of the patients are moving without dose interruption at all. And it's been a very important.

Ritu Baral -- Cowen -- Analyst

And is that still growing? Is that still growing, like those the home infusion rates?

Andy Orth -- Senior Vice President, Head of the U.S. Region

Yes. And maybe I can touch on the U.S. With that specifically, the answer is yes. As Barry mentioned, we've doubled it from 9% to 20%, essentially from the end of 2019 to currently. And we expect that to continue to grow. Our teams have been in site-of-care optimization mode since the onset of COVID. And that's both home care as well as more local infusion centers if they were going into larger institutions. So we expect our patients and physicians to continue to take advantage of home care.

Ritu Baral -- Cowen -- Analyst

And could you just go through reimbursement on the lab reimbursements of that? Yes.

John M. Maraganore -- Chief Executive Officer

Thank you.

Barry Greene -- President

So to your just in terms of growth, we as the pandemic ebbs and flows, both in the United States and other countries, we see patients move to home infusion and then when possible back to a local infusion center. And keep in mind that patients really like getting out of their house and the social aspect of the infusion centers. infusion centers.

John M. Maraganore -- Chief Executive Officer

Great. Thanks, Barry. Ritu, does that answer your question?

Ritu Baral -- Cowen -- Analyst

Yes. And I just wanted to could you just review reimbursement? Like...

John M. Maraganore -- Chief Executive Officer

Oh, reimbursement.

Ritu Baral -- Cowen -- Analyst

Yes, yes.

John M. Maraganore -- Chief Executive Officer

Do you want to handle that, Andy?

Andy Orth -- Senior Vice President, Head of the U.S. Region

Yes, certainly, certainly. So the reimbursement, clearly, on the commercial side of our population is very straightforward, and we have many patients there taking advantage of it. But we also know, right, that CMS released in late June a regulation that allowed a temporary reimbursement scheme for Medicare Part B patients. And we also have many hospitals that are beginning to take advantage of that, and that's an area where we expect to see more growth and utilization of that going forward.

John M. Maraganore -- Chief Executive Officer

Did that answer your question, Ritu?

Ritu Baral -- Cowen -- Analyst

Yes. Thank you so much.

John M. Maraganore -- Chief Executive Officer

Great.

Operator

We will now move to our next question from David Lebowitz from Morgan Stanley. Please go ahead. Your line is open.

David Lebowitz -- Morgan Stanley -- Analyst

Thank you very much for taking my question. Given your experience thus far for GIVLAARI, have you, I guess, made any decisions on lumasiran, what you might want to keep and what you might want to modify as far as the launch given the similarities of the market?

John M. Maraganore -- Chief Executive Officer

Yes. Great question. Let me make some initial comments, and then Barry you should comment as well. I mean obviously, lumasiran, like GIVLAARI, is addressing a very devastating disease that's an ultra-rare orphan population based on prevalence. As with GIVLAARI, there are the under-diagnosis rates in PH1 are also well known. And so there's a need for patient finding. We're we have a commitment, as you know, David, to be focused on the value that our medicines deliver. And we have been very successful in that approach, proactively engaging with payers, forming value-based agreements. And that effort will occur with all medicines in our pipeline, including lumasiran. And so as we begin to get ready for launch and get ready for this important new medicine to come in, the playbook that we developed for ONPATTRO, the playbook that we've been executing on for GIVLAARI is one that we will absolutely be using for lumasiran. Of course, we'll be leveraging importantly, leveraging the existing infrastructure that we've built now globally for the company. Barry, anything to add to that?

Barry Greene -- President

No, that's perfect, John. The only color I'd add, David, is that we've gotten very, very good now at the digital, virtual and site-of-care optimization that was made necessary for COVID. to the launch of a disease like PH1, where, again, while the diagnosis rate is 50%, there are 50% of patients out there undiagnosed. So being able to reach them in virtual means it's going to be highly advantageous.

John M. Maraganore -- Chief Executive Officer

Yes. Thanks Barry. David does that answer your question?

David Lebowitz -- Morgan Stanley -- Analyst

Fine, yes. Thank you for taking my questions.

John M. Maraganore -- Chief Executive Officer

Okay. thank you.

Operator

We will now move to our next question from Vincent Chen from Bernstein. Please go ahead. Your line is open.

Vincent Chen -- Bernstein -- Analyst

Thank you very much for taking the question. Two quick ones, one commercially oriented and one on the R&D side. First, for GIVLAARI, we realize you're not going to provide any guidance, but I'm curious what you're seeing as far as the trajectory of start forms coming out of Q2 and going into Q3. I know that incremental start forms slowed in Q2 relative to Q1. I imagine some of this is because you had an initial bolus of patients in Q1, some of it is impact from COVID that adversely impacted Q2. Just trying to get a sense for what a reasonable near-term run rate might look like between those 2. And then second, on the R&D side, a quick one on the ALN-APP IND filing. We've certainly been watching very closely for a move into the CNS delivery, which could open up a range of very large and high unmet need mitigations. So it seems like it's taken some time. What are the gating factors on the ALN-APP IND filing? What has to be done before you can enter human trials?

John M. Maraganore -- Chief Executive Officer

Yes. Those are great questions. Let me start with the first one. Akshay, you'll get the second one just in a minute. But your question on GIVLAARI, I mean we're extremely pleased with the performance that we saw in Q2, even though we were going through the pandemic. And keep in mind, Vincent, that the start forms that we saw in Q1, of course, were benefited greatly by patients that were either in the U.S. EAP or that were known to site, sort of that initial bolus, if you will. But we do expect growth from that point that we're seeing continued growth in the U.S. About 25% of our patients in the U.S. are also coming outside of our patient hub, and therefore, they're not on the start form metric, if you will. And that accounts for the over 100 patients that we believe are now on GIVLAARI commercial treatment. Now that includes a small part of the U.S.

We're as we said in our prepared remarks, we're now going to stop providing start form metrics for GIVLAARI, just like we did with ONPATTRO last year, because we now have a global source of patients, not just the U.S. alone and we still have a significant number of patients that are coming outside of our patient hub. But you'll see the growth in our total patient number quarter-on-quarter for GIVLAARI, and we are optimistic with that growth in the U.S. and also in other markets around the world. Now Europe, of course, it has now been launched in Germany and made patient sales around many countries. So I think that we don't need say anything more about GIVLAARI. Do you want to now, Akshay, talk about APP and what's between now and our filing?

Akshay Vaishnaw -- President, Research and Development

Sure. Yes. I mean we a bit of an echo. We're delighted with the progress, Vincent. It's about a year since we signed the deal with Regeneron. Next year is exciting and we think represents good progress. What we have to do now is simply complete the toxicology and CMC packages. We've already had good engagement with regulators, and so we're looking forward to filing that IND in due course in mid-2021.

John M. Maraganore -- Chief Executive Officer

Does that help, Vincent?

Vincent Chen -- Bernstein -- Analyst

Yes. Very helpful. Thank you very much.

John M. Maraganore -- Chief Executive Officer

Alright. Thank you.

Operator

And we'll now move to our next question from Salveen Richter from Goldman Sachs. Please go ahead. Your line is open.

Salveen Richter -- Goldman Sachs -- Analyst

Good morning. Thanks for taking my question. And Barry, you'll be missed here. So in the context of competitive dynamics in PNH, how are you thinking about your upcoming study looking in this setting and what would be meaningful to be differentiated here or where you could fit in, in the treatment paradigm? And then just a comment on based on your work in extrahepatic tissues where you feel most optimistic at this point.

John M. Maraganore -- Chief Executive Officer

Great. Thanks, Salveen. Well, let me start and then, Akshay, you can comment as well. On the first question with the work that Regeneron is leading with cemdisiran and pozelimab. I mean, look, there is no subcu alternative that's currently approved today. This is an opportunity to having a subcu treatment for complement-mediated diseases with a very infrequent dose regimen, even with potential for combination of the two drugs. We feel very, very encouraged by data that from both animal studies, but even from human studies that would suggest that combination of an RNAi-based approach with an antibody approach would provide very significant protection in against the complement pathway with an infrequent subcu dose regimen. So I'll stop there. Akshay, maybe you can comment on that, but also on our extrahepatic work and where we're most confident these days.

Akshay Vaishnaw -- President, Research and Development

Yes. So certainly, in frequent presentation, I also think that we have the opportunity to have the most complete blockade of the complement system and hopefully the best efficacy profile. Now the current drugs already have good efficacy, but we'd like to see no breakthroughs for these patients and for them to be able to maintain their hemoglobin levels without need for any transfusion at all. And we think complete blockade in the form of a combination product could offer that. Looking beyond PNH and at the extrahepatic pipeline. We just touched on the CNS. It is indeed exciting that within a year of announcing that deal with Regeneron on CNS, on ocular, we've now announced that we'll be filing an IND next year for the nervous system. That will be the first of many, we think. We have very exciting data in the ocular compartment as well.

And most recently, of course, we shared data on one delivery. So I can't really say one is my favorite, but a recurring theme for us over the years has been that when we've had strong replicable data in animal systems, first in rodents and then in the non-human primate, that then has invariably led to translation in the human setting. And so with all three compartments, as these INDs have hit the clinic, we're looking forward to replicating the success of our work in the liver with evidence of knockdown clinical efficacy and safety in the brain, in the eye, in the lung, etc. And we're not going to stop there. Of course, we have many other efforts ongoing for other compartments, which we will get to in due course. So that's just a little bit on the extrahepatic thinking.

John M. Maraganore -- Chief Executive Officer

I would just add to that part that what's exciting about the CNS opportunity, of course, is that there are many neurodegenerative diseases that are gain-of-function proteinopathies with genetic validation. And we have shown in nonhuman primates some exciting data that we fully expect we'll replicate in the human setting based on our past experiences. And what's really key there is the durability that we see. That is going to be important because with intrathecally administered drugs, being able to have significant knockdown of the pathogenic protein with infrequent dose administration is going to be something which is highly differentiated, not only for the APP program that will be the first one to go, but the Huntington's program that will come shortly thereafter and programs that we're obviously advancing in diseases like ALS and Parkinson's and Alzheimer's, etc. So this is really going to be an exciting story for the company. And we do expect, starting in 2021, to have one to two INDs per year that are coming out of that CNS ocular Regeneron pipeline together with them. So it is an exciting new frontier for the company.

Salveen Richter -- Goldman Sachs -- Analyst

Great. Thank you.

John M. Maraganore -- Chief Executive Officer

Thanks Salveen.

Operator

We will now take our next question from Gena Wang from Barclays. Please go ahead. Your line is open.

Gena Wang -- Barclays -- Analyst

Thank you for taking my questions. First, Barry, great working with you over past many, many years. My best wishes to your next journey. Yvonne, certainly looking forward to working with you more. I have two questions. One is ONPATTRO. Just wondering if you can share how much revenue is contributed from Japan. And then for vutrisiran, wondering any COVID-19 impact on collecting the data.

John M. Maraganore -- Chief Executive Officer

Great, great question. So let's Jeff, why don't you answer the first question, and then Akshay, you can answer the HELIOS-A question secondly. Go ahead, Jeff.

Jeff Poulton -- Chief Financial Officer

Yes. If I heard the question correctly, the question was about Japanese contribution to ONPATTRO revenue in the quarter. We don't break out the detail by country, Gena, but Japan was a meaningful contributor to the growth that we saw outside the U.S. in the quarter. And we highlighted in the prepared remarks that Japan now has become the second-largest market for ONPATTRO on a dollar sales basis based on the Q2 result.

John M. Maraganore -- Chief Executive Officer

And Akshay, do you want to comment a little on the vutrisiran management of the study?

Akshay Vaishnaw -- President, Research and Development

Yes. I mean both for vutrisiran and patisiran in their respective cardiomyopathy studies, maintaining study integrity, obviously, has been of the highest priority during this COVID period. And we've used a variety of approaches successfully, telemedicine, where physicians in the site speak to patients over the phone and other means. We've had home administration of drug. And there's, of course, the ability to take blood samples at home. And finally, for key visits that require in-clinical assessment, we always build in a little bit of buffer around the timing of the visits. So they don't have to come in exactly on a given date. It can be a few days or a few weeks before or after depending on the endpoint. So using these different means, it's not been trivial, but we've certainly maintained study integrity, and we're pleased with that. And we're also pleased with the fact that with things opening up, as we've seen on the commercial side, we're seeing very good pickup in enrollment as well in these studies.

John M. Maraganore -- Chief Executive Officer

Yes. And I would just to make because I think, Gena, your question was also focused on HELIOS-A, which, of course, was completed.

Akshay Vaishnaw -- President, Research and Development

Oh, sorry.

John M. Maraganore -- Chief Executive Officer

Yes, completed the enrollment. We're still on track for early 2021 data from that. And we've, obviously all the things that Akshay just commented on, of course, have been critical in terms of making sure that we maintain data integrity and no missed doses or minimal missed doses during the course of that study. So that's what applies to HELIOS-A.

Gena Wang -- Barclays -- Analyst

Thank you.

John M. Maraganore -- Chief Executive Officer

Great. Thanks Gena.

Operator

We'll now move to our next question from Alan Carr from Needham & Company. Please go ahead. Your line is open.

Alan Carr -- Needham -- Analyst

Hi, thanks for taking questions and congratulations, Barry. I'll miss you. So you mentioned that you've submitted IND for the HSD program. There's been a development, regulatory challenges around NASH. I'm wondering if you can give us some update on your plans and strategy on that one, how you differentiated that.

John M. Maraganore -- Chief Executive Officer

Great. Thanks, Alan. So Akshay, that question was on ALN-HSD and NASH and our plans there. Do you want to comment further?

Akshay Vaishnaw -- President, Research and Development

Yes. So Alan, we're excited to have filed the IND CTA and get going with this program. We are excited about the target because it's a genetically validated target and uniquely so, I think, in the NASH landscape compared to many of the other targets that have been addressed to date, and most of which have fallen short, unfortunately. And HSD17B13 seems to be a gateway to the later consequences of the accumulation of hepatic fat. So you have a 50% knockdown because we know heterozygous loss of function protects people from NASH. We think even 50% knockdown should be sufficient. But we know from our liver programs, we can do a lot better than that.

And we know we can achieve greater than 50% from our animal work with our drug candidate. So it's great to get this to the clinic. Phase I will be all about safety, PK, and we'll collect a number of exploratory biomarkers. HSD17B13 itself is not a target that's secreted into the circulation, but we have some very good exploratory biomarkers markets that will help assess the target engagement. And then from that, we'll go into Phase II, and that's where we'll have a dose and regimen selected, which I imagine will be a low dose given rather infrequently given the profile of the drug we're seeing in animals, once every three months or six months or so. And that's where we'll test the key hypothesis of preventing progression to NASH itself. But those details are to come. For now, we have to focus on the Phase I.

Alan Carr -- Needham -- Analyst

Okay. That is all my question.

John M. Maraganore -- Chief Executive Officer

Thanks Alan.

Operator

We will now take our next question from Mani Foroohar from SVB Leerink. Please go ahead. Your line is open.

Mani Foroohar -- SVB Leerink -- Analyst

Thanks for taking my question and Congrats, Barry and Yvonne as well. Although with Barry gone, I guess, Yvonne, you got to be much better telling me how I'm wrong all the time about everything. A quick question about ONPATTRO. Obviously, there was a little bit of a decline in terms of patient adherence, which is not surprising. I know the PK of RNAi assets is very unique in terms of pharmacokinetics versus other drugs. Is there an avenue to any catch-up dosing and these patients potentially getting back temporarily on an IV dosing schedule that could be a little more frequent than what's labeled? I.e., could you recapture some of that lost revenue? Or do you think people will end up back on the on-the-label-dosing frequency? And then secondarily, in thinking about HELIOS-B, you guys have you talked about the potential interim, when that would look like. How do you think about timing to make a decision on whether or not to take that voluntary interim? And on what time horizon might you be just telling us, "hey, we're going to be taking interim or not," in terms of just giving us some sense of when we should expect that event?

John M. Maraganore -- Chief Executive Officer

Yes. Those are great questions. Maybe on the first one, Mani, I mean your question makes sense, of course. But I think that it's our expectation that patients would stay on label and do q3 weekly dosing. We have no reason to believe that, that would change whatsoever. And we've heard nothing about that in the field. So but I think the good news is that adherence rates, some missed doses that occurred in Q2 are showing great strength as we enter Q3. And we don't expect to see any significant impact like that we experienced during the pandemic phase. So I think that's really behind us at this point in time. Andy, do you want to comment any further on that? I think I covered it, but you might have some other perspective.

Andy Orth -- Senior Vice President, Head of the U.S. Region

No, John. You covered it right. Everything we're hearing is a resumption to the original schedule for any folks who were paused for whatever reason.

John M. Maraganore -- Chief Executive Officer

Yes. And then your second question on HELIOS-B also one that makes a lot of sense. But very specifically on HELIOS-B, we will do an interim analysis. We made the commitment to do that. Now we've left it open with the agency on exactly how that will be designed. And we're not going to comment yet on timing. And I'll just say again that one of the benefits of the APOLLO-B study is that as we read out data from that study, it will inform how we should think about the interim analysis for HELIOS-B specifically. Akshay, do you have anything else to add to that?

Akshay Vaishnaw -- President, Research and Development

No, no. Nothing to add.

Mani Foroohar -- SVB Leerink -- Analyst

Thanks guys.

John M. Maraganore -- Chief Executive Officer

Thank you.

Operator

We will now take our final question from Navin Jacob from UBS. Please go ahead. Your line is open.

Sriker Nadipuram -- UBS -- Analyst

Hi everyone. Thanks for taking the question. This is Sriker Nadipuram on for Navin Jacob. Just on ONPATTRO, Yvonne mentioned combination therapy and you previously stated that ONPATTRO. Can you give us an update of what percentage of patients are on both now? And can you tell us anything on the outcomes of these patients versus patients on just monotherapy?

John M. Maraganore -- Chief Executive Officer

Okay. So let me start on the combination use that's occurring out there as we hear from the marketplace. These are studies where specific data are being generated. We're just aware that patients that have a mixed phenotype, where they've got polyneuropathy, are receiving ONPATTRO. And in some cases, those patients are also on a TTR stabilizer. So we're just aware of that, and we have market research that says that it's somewhere in the range of 15% to 30% now, and it could double by the end of the year. We just recently published some data on combination use with from our previous Phase II open-label study. And that published paper showed that the combination was safe and the level of TTR knockdown was as good as monotherapy. But there was no formal assessment of or was it powered to show anything on the efficacy side. So I don't think anything can be concluded at this point in time about any improved activity. But Andy, do you want to comment a little bit further on dynamic on concomitant use that we're seeing in the marketplace?

Andy Orth -- Senior Vice President, Head of the U.S. Region

And I'll just add....

John M. Maraganore -- Chief Executive Officer

I'm sorry, Andy. Just one thing is I want to highlight also that this is really a U.S. phenomenon. We don't see this in the rest of world. But Andy, go ahead.

Andy Orth -- Senior Vice President, Head of the U.S. Region

Right. Great. Yes, happy to. So since the fourth quarter of 2019, in the U.S., we've been seeing growing evidence of reimbursement for ONPATTRO were used concomitantly with TTR stabilizer products, which at the end is a positive for patients with multiple manifestations of the disease. And barring any unforeseen changes due to COVID or other, we expect concomitant use to continue to increase in the U.S. over time for patients whose disease manifestations include polyneuropathy. And as John said, right outside of the U.S., it's more of a switched dynamic.

John M. Maraganore -- Chief Executive Officer

Right. And then your pricing question. Jeff, do you want to handle that?

Jeff Poulton -- Chief Financial Officer

Yes. Sure. The comment on ONPATTRO for Q2 was that there was a very modest increase in gross to nets relative to Q1, which created a slight headwind in growth quarter-to-quarter. There is variability in gross to net quarter-to-quarter. We've talked about that on the last several calls. It's just based on the way the accounting works and the estimates and the true-up of those estimates. But we're very confident that the full year gross to nets for ONPATTRO will be very consistent with what we experienced in 2019, and the expectation is mid-20s for the year.

John M. Maraganore -- Chief Executive Officer

Great. Does that answer your questions?

Sriker Nadipuram -- UBS -- Analyst

Yes. Thanks very much.

John M. Maraganore -- Chief Executive Officer

Okay. So with that, we're going to close our call, thank everyone for joining us on the call and, again, to all of our employees for their dedication and their hard work. Of course, Barry, we wish you all the best in your next chapter. And Yvonne, so excited for you in this expanded role at Alnylam. So with that, we look forward to updating you in future calls on our progress. And please stay safe and please stay healthy. Bye-bye now.

Akshay Vaishnaw -- President, Research and Development

Bye, everyone.

Operator

[Operator Closing Remarks]

Duration: 76 minutes

Call participants:

Christine Regan Lindenboom -- Investors and Media

John M. Maraganore -- Chief Executive Officer

Barry Greene -- President

Akshay Vaishnaw -- President, Research and Development

Jeff Poulton -- Chief Financial Officer

Andy Orth -- Senior Vice President, Head of the U.S. Region

Yvonne Greenstreet -- Chief Operating Officer

Paul Matteis -- Stifel Nicolaus -- Analyst

Alethia Young -- Cantor Fitzgerald -- Analyst

Anupam Rama -- JPMorgan -- Analyst

Tazeen Ahmad -- Bank of America Securities -- Analyst

Maury Raycroft -- Jefferies -- Analyst

Ritu Baral -- Cowen -- Analyst

David Lebowitz -- Morgan Stanley -- Analyst

Vincent Chen -- Bernstein -- Analyst

Salveen Richter -- Goldman Sachs -- Analyst

Gena Wang -- Barclays -- Analyst

Alan Carr -- Needham -- Analyst

Mani Foroohar -- SVB Leerink -- Analyst

Sriker Nadipuram -- UBS -- Analyst

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