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ObsEva SA (OBSV -60.00%)
Q1 2019 Earnings Call
May 9, 2019, 8:00 a.m. ET
Contents:
- Prepared Remarks
- Questions and Answers
- Call Participants
Prepared Remarks:
Operator
Welcome to the ObsEva First Quarter 2019 Financial Results and Business Update Conference Call. All participants are currently in listen-only mode. Following management's prepared remarks, we will hold a Q&A session. (Operator Instructions) As a reminder, this call is being recorded today, May 9, 2019. I would now like to turn the conference over to Mario Corso. Please go ahead.
Mario Corso -- Senior Director, Investor Relations
Thank you, operator. This is Mario Corso, Senior Director, Investor Relations at ObsEva. Good morning to our listeners in the United States, and good afternoon to those of you joining us from Europe. Welcome to today's call to review ObsEva's first quarter 2019 financial results.
On this call, I'm joined by Ernest Loumaye, our Co-Founder and Chief Executive Officer; Jean-Pierre Gotteland, our Chief Scientific Officer; WimSouverijns, our Chief Commercial Officer; and Tim Adams, our Chief Financial Officer.
During today's call,ObsEva management will be making forward-looking statements, including but not limited to statements relating to financial results and trends, the process and timing of anticipated future development of ObsEva's product candidates; our oxytocin receptor antagonist nolasiban; our gonadotropin-releasing hormone receptor antagonist, linzagolix; and our prostaglandin F2 alpha receptor antagonist, OBE022.
These forward-looking statements will include comments about expected clinical trial results and regulatory pathways in the United States, Europe and Asia as well as the therapeutic and commercial potential of ObsEva's products. These forward-looking statements are based on ObsEva's current expectations and they inherently involve significant risks and uncertainties. ObsEva's actual results and the timing of events could differ materially from those anticipated in such forward-looking statements.
Risks and uncertainties include, without limitation, those related to ObsEva's development programs, clinical trial timelines and results, the uncertain clinical development process including adverse events, the success cost and timing of all development activities in clinical trials, the market potential for ObsEva's product candidates, the accuracy of ObsEva's estimates regarding expenses, capital requirements and the need for financing and other risks detailed in the Risk Factors and elsewhere in ObsEva's filings with the US Securities and Exchange Commission, including its 6-K report for the three months ended March 31, 2019 to be filed on or around May 9, 2019, as well as other reports filed on Form 6-K and 20-F. ObsEva undertakes no obligation to update any forward-looking statements as a result of new information, future events or changes in expectations, except as required by law.
I will now turn the call over to Ernest Loumaye, ObsEva's Chief Executive Officer.
Ernest Loumaye -- Chief Executive Officer
Good morning, everyone. Thank you, Mario. I'm pleased to have the opportunity to review our first quarter progress with you. 2019 promise to be a defining year for our Company, and our work in the first quarter support our momentum as well as our ability to deliver on this promise. I would start with nolasiban. As you likely know, we are currently conducting a second registration trial after recording positive results on the first registration trial in 2018. A positive outcome in the second trial would drive our first submission for commercial approval in Europe.
In support of these major milestones, last December, we announced the initiation of the second confirmatory Phase III trial with nolasiban in Europe called IMPLANT 4. The IMPLANT 4 trial is planned to enroll approximately 800 patients while undergoing a Day 5/single embryo transfer and would involve some 40 centers across Europe, Russia and Canada.We are pleased that initial centers and patient interest in enrolling IMPLANT 4 has been very strong, and we anticipate that patient enrollment may soon be completed, with primary endpoint results slated, as initially planned, for the fourth quarter of 2019.
Upon positive ongoing 10-weeks pregnancy primary endpoint results for IMPLANT 4, our plan is to proceed with the marketing authorization applications filing in Europe by the end of 2019.Also of note, we recently announced the final safety follow-up from the IMPLANT 2 trials, which shows no different from placebo in developmental health of infant follow-up for six months post-birth as measured by the Age & Stage Questionnaire third edition or ASQ-3 score.
Regarding nolasiban in the US, we continue to work with the FDA to finalize the design and scope of the Phase III development program. We believe we are on track to convey the feedback and pass the word by the end of the second quarter, with plans to initiate US clinical development in second half of 2019.With nolasiban, we are developing a product that has the potential to make a significant impact on couples suffering from infertility. We believe that 35% increase in live birth rates seen with the five single embryo transfer in IMPLANT 2 represent a huge improvement over current IVF success.
Further, infertility is a global problem. It is estimated that worldwide infertility affects about 10% of reproductive-aged couples, and more than 2 million ART cycles are performed each year globally, a number that is growing. The largest markets are Europe and China at approximately 800,000 annual treatment cycles each, with another 240,000 per year in the United States. These major markets hold great importance for us, although with different timeline, and we believe a relatively small commercial organization can address the US and Europe, given the concentrated nature of IVF centers.
Looking now at linzagolix and our ongoing development in uterine fibroids and endometriosis. As we have said before, the data to-date indicate we are looking at a potential best-in-class all oral GnRH receptor antagonist that will afford dosing option with and without low dose add-back therapy or ABT. It is important to note that the choice whether or not to use add-back therapy is important to both physicians and patients and the evolving body of data for linzagolix support the potential for this choice.
The capacity of linzagolix to address the symptoms of a majority of patients with endometriosis through partial suppression of estradiol, and no need for ABT is supported by our Phase IIb EDELWEISS trial showing that linzagolix 75 milligram dose appears to offer potential symptomatic relief in nearly three-quarters of endometriosis patients at a level of bone loss that would not be expected to require add-back therapy issues clinically.
Clinically, this is important because there are health risks associated with add-back therapy risk that a significant majority of patients may not need to assume. For the minority of patients requiring full suppression to achieve symptomatic relief, we are evaluating a 200-milligram dose of linzagolix. This dose would require ABT to protect against bone mineral density loss.
This dosing strategy that we're pursuing has been recently further supported by a model-based analyses that correlate the impact of E2 levels with additional response to both menstrual and non-menstrual pain as well as decline in BMD. This analyses indicate that a 75 milligram and 100 milligram dose of linzagolix, menstrual and non-menstrual pain and uterine fibroids can be effectively handled (ph) without significantly compromising blood. And yet at higher dose level, on the other hand, BMD loss starts to accelerate.We believe this strongly support our dose selection strategy with an option to achieve symptoms relief without the need for add-back therapy, 75 milligrams in endometriosis and 100 milligrams in uterine fibroids and the higher dose of 200 milligram as needed with concomitant use of add-back therapy in order to preserve bone health.
Thus, based on our Phase IIb result and modeling work, our proposed therapeutic strategy for endometriosis as well as uterine fibroids would be for patient to start on a lower dose as first-line therapy and only increase the dose with concomitant add-back therapy if symptoms relief is not achievable at lower dose. Moreover, we recently announced the final endpoints for the EDELWEISS trial long-term follow-up, which include patient dose for 52 weeks as well as patients who were followed up for six months off-treatment post receiving lizagolix for six months treatment period. The 52 weeks treatment data was consistent with the initial six months results, showing durable efficacy and the BMD impact that would be expected from partial and full suppression of estrogen. The six months follow-up off-treatment suggests persistent efficacy beyond treatment completion and bone mineral density increase.
Following interaction with the FDA, we are presently initiating two Phase III trials for endometriosis associated pelvic pain known as EDLWEISS 2 and EDLWEISS 3, which combined would, in the whole, approximately 900 patients in the US and Europe.As reported last quarter, we continue to advance our two ongoing Phase III trials of linzagolix, PRIMROSE 1 and 2 for the treatment of heavy menstrual breeding due to uterine fibroids. We announced in December that PRIMROSE 2 completed patient enrollment in Europe and the US. PRIMROSE 1 is a US only trial and we continue to expect patient recruitment to be completed this quarter.We continue to anticipate announcing six months primary endpoint results from PRIMROSE 1 in the fourth quarter of 2019 and PRIMROSE 2 results a few months later in Q1 of 2020. The timing of this data readouts supports our planned US (inaudible) submission in late 2020, which assumes data with 12 months of treatment for chronic indication.
I would like to highlight that our uterine fibroid Phase III program is the only one utilizing a non-add-back regimen of a GnRH antagonist, which is being undertaken in the interest of exploring whether a significant proportion of patients might experience symptomatic relief with partial estrogen suppression thereby not requiring ABT to protect BMD.Should this be the case, we believe it would significantly contribute to the differentiation of linzagolix within the class.
In summary, on linzagolix, endometriosis and uterine fibroids impact millions of women both the US and Europe, and the unmet needs remain high as current treatment include oral contraceptive and (inaudible) and short-term GnRH agonist therapies offer only limited effectiveness and core safety tolerability limitation.
Moving now to OBE022. As you know, OBE022 is being evaluated for the treatment of preterm labor and the proof-of-concept Phase IIa trial being conducted in two parts; Part A and Part B. In late January, we announced results from part A of the trial, which shows that OBE022 was really well tolerated by mother and their fetuses and demonstrated that the pharmacokinetics of the drug are similar to those previously observed in non-pregnant women.
Based on this result, we initiated Part B of the trial. Part B is a multi-center, randomized, double-blind, placebo-controlled, parallel group trial that we ran whole up to 120 patients with preterm labor at the gestational age of between 24 weeks and 34 weeks. The trial design will assess efficacy, safety and pharmacokinetics. Efficacy is defined as the ability to delay preterm delivery by at least seven days, allowing for treatment of the mother and fetus to protect organ development.
Part B will receive either OBE022 or placebo with a starting dose of 1000 milligrams initially followed by 500 milligrams twice a day for seven days to women already receiving atosiban infusion for 48 hours. We are enthusiastic about the Part A results that shows that eight of nine patients were able to make it through the seven-day dosing period without delivery. And we look forward to interim analyses result by the end of this quarter in a subset of 30 patients.
As we have previously stated, we anticipate making a go-no-go decision on development of OBE022 later this year based upon the results of the first 60 patients enrolled in this trial. Preterm labor is a significant medical issue that continues to grow in importance as the average ages of mothers in western societies increase and associated costs in the US, for example, are in the billions of dollars given the high price of neonatal intensive care in United States.There are few safe and effective treatments available for this condition with only atosiban approved as a tocolytic in Europe and essentially no approved acute therapy in the US,all of which drives our enthusiasm for developing new option, such as OBE22 for this patient population.
In summary, we continue to make steady and important progress with three NCEs in our pipeline, executing well against milestones, delivering promising clinical data and planning regulatory application that can lead to commercialization.
I would now turn the call over to our Chief Commercial Officer, Wm Souverijns, who will share some updates on our planning and preparation for commercialization.
Wim Souverijns -- Chief Commercial Officer
Thank you, Ernest. Since joining ObsEva in November, it has been a very busy few months and I would like to share with you some of the initial planning that we've been working on. First priority has been to prepare for commercialization of nolasiban in Europe. To that end, we have initiated the build-out of our global commercial team starting with three key functions; medical affairs, market access and marketing.
Assuming a positive readout from our IMPLANT 4 trial later this year, we will start hiring key people in the priority EU markets in preparation for the potential launch in early 2021. As I mentioned on our last call, a prime motivating factor for me to join ObsEva was the potential of nolasiban to positively impact the lives of couples suffering from infertility and particularly women undergoing IVF.
In order to enable that, once approved, it is essential to establish a strong value proposition for nolasiban underpinned by robust pharmacoeconomic evidence. Key drivers of that value proposition are the increasing IVF productivity as well as achieving live birth rates with single embryo transfer that are comparable to or even higher than with double embryo transfer without a high rate of multiple pregnancies.
We've initiated work with IVF stakeholders to gain feedback on our value proposition and are developing an outreach plan in order to validate our perspectives with them. Our objective is to create a win-win-win opportunity for all relevant parties in IVF; for women to have a higher likelihood of taking home healthy baby; for clinicians and centers to offer superior live birth rate results and for payers to save costs associated with IVF.Beyond that, we should not forget the societal value of improving IVF outcomes in light of the need to increase population fertility rates to sustain the economy in most developed countries. Sufficed to say that I'm now even more excited by the potential of nolasiban and the impact it can have on such an important area of not only healthcare, but even society.
In summary, we believe that the concept of utilizing nolasiban as a therapy to increase rates of pregnancy and live birth, whilst at the same time providing a cost benefit by utilization of single embryo transfer and minimization of multiple pregnancies and their associated morbidities is a strategy that will resonate among patients, centers and payers alike.
Let's now move to linzagolix, we are very excited about the readout of the Phase III PRIMROSE trials in uterine fibroids later this year, targeting NDA filing for this indication by year-end 2020. On top of that, we are now beginning Phase III trials in endometriosis.Our primary objective is to differentiate linzagolix from the other oral GnRH antagonists. The key message is the ability to address symptoms of bleeding and pain in a majority of patients with uterine fibroids and endometriosis respectively without the need for add-back therapy.
The data described by Ernest earlier suggests that the PK/PD profile of linzagolix is ideally suited to accomplish this with a simple, single once-daily oral dose of linzagolix, 75 milligrams for endometriosis, and 100 milligram for uterine fibroids. In light of the tendency of women and clinicians to try avoiding the use of exogenous hormone therapies, such a profile could truly set linzagolix apart from the other oral GnRH antagonists.
Finally, on OBE022, we are in the early stages of development for this compound, but the unmet medical need is very significant. While the ICU cost burden of preterm labor often places it in the top five cost drivers at delivery centers. We're looking forward, therefore, to the interim efficacy data soon in the first 30 patients that will help guide the next step in development and commercialization.
Summing up, in a time where women's health issues are under served, we believe that our broad and truly innovative pipeline can make a real difference in women's lives, and we're excited about the major pipeline milestones that lie ahead.
On that note, I will now turn the call over to our CFO, Tim Adams for a brief financial review.
Tim Adams -- Chief Financial Officer
Thank you, Wim. Good morning or good afternoon everyone and thank you for joining us on the call today. I'm going to spend a few minutes now discussing our financial results for Q1 of 2019. Our net loss for the first quarter of 2019 was $25.7 million or $0.59 per share. This compares with a net loss of $19.8 million or $0.54 per share for the first quarter of 2018.
Factors that contributed to the year-over-year change included increased spending on clinical development for nolasiban and linzagolix, equity-based compensation, new employee hiring and professional fees related to market research and pre-commercial activities. Research and development expenses were $20.1 million for the first quarter of 2019 versus $16.3 million for the first quarter of 2018. This increase is attributed to the continued investment in clinical trial development for nolasiban and linzagolix.
G&A expense in the first quarter of 2019 was $5.3 million as compared to $3.6 million for the first quarter of 2018. Our cash balance as of March 31, 2019 was $117.3 million and in line with our expectations. Cash used in operations during Q1 was $20.9 million and reflects spending in support of all three of our pipelined assets, which includes the patient follow-up of our Phase IIb EDELWEISS trial in endometriosis as well as the initiation of EDELWEISS 2 and EDELWEISS 3 Phase III trials; the ongoing Phase III enrollment of the PRIMROSE clinical trials for the treatment of uterine fibroids; the completion of neonatal and infant follow-up in Phase III IMPLANT 2 clinical trial of nolasiban as well as the enrollment of the confirmatory Phase III IMPLANT 4 trial; completion of Part A and enrollment in Part B of the PROLONG trial of OBE022 in preterm labor; an initial pre-commercial spending related to nolasiban for the IVF indication in Europe.
Current cash on hand is expected to fund our operations into mid-2020, and we expect our use of cash for 2019 will be approximately $100 million. This cash use largely reflects expanding investment in our pipeline activities with as many as six Phase III trials expected to be ongoing during the year as we approach regulatory filings for two of our three compounds in 2019 and 2020.
Thank you all again for your continued support of ObsEva. And operator, we are now ready to open the line for questions.
Operator
Thank you. (Operator Instructions)
Tim Adams -- Chief Financial Officer
Operator, it's Tim Adams. Before we go into Q&A, I just want to remind all of our investors, we have a very busy conference schedule coming up for May and June. We will be at the RBC Conference in New York May 21 and 22. Couple of weeks later, we'll be back in New York at Jefferies, June 4th through 7th. Then at the end of June, on the 25th, we'll be back again for the BMO conference. So we certainly hope to see everyone there.
And operator, I have one minor correction from our prepared comments earlier.When we were describing the six-month primary endpoint results for the PRIMROSE 1 and 2 studies,it's actually PRIMROSE 2 that will read out first in Q4 of this year followed a couple months later in Q1 of 2020 will be the PRIMROSE 1, and I think we had just inverted those comments earlier.
So operator, with that we are ready for questions.
Questions and Answers:
Operator
Thank you. Our first question comes from Kennen MacKay from RBC Capital Markets. Your line is open.
Justin Burns -- RBC Capital Markets -- Analyst
Hi, this is Justin on for Kennen. Thanks for taking the questions and looking forward to having you guys in New York in a few weeks. First one, given the strong launch so far for elagolix and the discussions that you've been having with physicians in the United States, I was wondering if you could give us a sense for how many patients that are currently receiving elagolix that you estimate those physicians would rather have a lower dose option that wouldn't require add-back therapy and then a follow-up on nolasiban if I can.
Wim Souverijns -- Chief Commercial Officer
Hi, Kennen, it's Wim here. We obviously don't have very good insight into the Orilissa launch being this done by AbbVie. What we do know is though that majority of the prescriptions are actually for the lower dose. So that is really aligned with our strategy to manage the symptoms in a majority of patients without the use of add-back therapy,so fully aligned with how we see the market is evolving and bodes well for our development plan.
Justin Burns -- RBC Capital Markets -- Analyst
Awesome, thank you.And then just quickly on the potential nolasiban launch in Europe, I was wondering sort of what market -- what markets you plan on targeting first there and what portion of the population those initial entry points represent?
Wim Souverijns -- Chief Commercial Officer
I'll take that question too. So our first target is, I would say, Western Europe essentially. So the Big 5 in Europe. The mid-sized markets like the Nordics, Benelux, Switzerland and Austria. And then following that, we will expanse more into Eastern Europe. In terms of the launch sequence, as you probably know that's really driven partly by reimbursements. Some markets, once you get an approval, it will take a time before you actually get to commercial launch because you got to go through negotiation.Now in this case, IVF is a bit of a particular market in that it doesn't follow necessarily the same patterns as traditional medicines. As one example, Spain, which typically would be a later launch market, in our case becomes a priority because about 85% of the market is private. That's important because Spain as a major country has one of the most -- the highest level of IVF procedures.So I would say, to summarize, we're going to go the traditional way through the market like Germany, France, Italy, the Nordics. But a country like Spain, which are very big, actually will come much earlier than other pharmaceutical markets.
Justin Burns -- RBC Capital Markets -- Analyst
Great, thank you.
Operator
Thank you. Our next question comes from Ami Fadia from SVB Leerink. Your line is open.
Xiaozhou Fan -- SVB Leerink -- Analyst
Hi, this is Sheldon on for Ami. Thanks for taking our questions. Just a quick question about linzagolix, could you remind us, other than the primary endpoints, what are your key secondary endpoints that we should look out for and how would those inform the field about the major differentiation factor for linzagolix?
Ernest Loumaye -- Chief Executive Officer
Yes, Ernest speaking. As you know, the primary endpoint in the Phase III program will be co-primary with the objective to reduce pain during menstrual period and reduce pain in non-menstrual period. Now, this is the primary endpoint, but there are long list of secondary endpoints, which are us really assessing the benefits for the patient beyond this abdominal pain and that includes pain during sexual intercourse, dyspareunia or pain after defecation which is called dyschezia. In addition, we are also looking for different questionnaire assessing the well-being and quality of life of these patients. And indeed, you remember that reporting on EDELWEISS, our Phase IIb, which show a consistent improvement in the perception by the patient that they feel better and their condition is less severe. So that's the panel of parameters we are assessing for the efficacy of the drug. Does that answer your question?
Xiaozhou Fan -- SVB Leerink -- Analyst
Yeah, thank you. Can I have a follow-up on your non-dilutive financing progress, you talked about that before. I'm wondering if you have any update for us.
Tim Adams -- Chief Financial Officer
Yeah. Hi, it's Tim. So we are making good progress in our discussions with various third parties who have been very supportive of the Company. There are two categories. One is venture debt and the second is royalty financing. There has been some very nice interest, and we are moving ahead. So it is a priority for us. We haven't announced anything yet. And certainly, when we have something to announce to the market, we will do that. But I feel good about the progress so far.
Xiaozhou Fan -- SVB Leerink -- Analyst
Thank you.
Operator
Thank you. Our next question comes from Martin Auster from Credit Suisse. Your line is open.
Mark Connolly -- Credit Suisse -- Analyst
Hi, this is Mark on for Marty. Thanks for taking my questions. First, I was wondering can you frame how we should think about the launch dynamics and the launch trajectory for the oral GnRH receptor antagonist class in uterine fibroids and compare this to endometriosis? And then I have a follow-up.
Ernest Loumaye -- Chief Executive Officer
Ernest speaking, and then I would ask Wim also to compare the trajectory of launch of endometriosis versus fibroids, I would tend to think that the endometriosis need is slightly higher for a new medical treatment than the fibroids' needs. For two reasons, that younger women, it's a permanent pain and really the treatment actually are not meeting the needs. Fibroids, it's older women would then to be accustomed to that increasing menstrual blood flow and they do not necessarily observe initially that this increase. And it's so true that in European population, we -- when the patient consult for fibroids, about 40% will already some level of anemia and 10% will have hemoglobin below 10 shows that they are just coping with that.
So I think awareness will be important and motivation of patient to say look, it's not normal to have that much bleeding needs to be also reinforced. Also because there is a competition with surgery, everybody wants to avoid surgery if possible, but surgery is still effective in fibroids and that about 200,000 or 250,000 hysterectomy, for example, every year in United States are performed for fibroids. So maybe Wim, you can add something on that.
Wim Souverijns -- Chief Commercial Officer
Yeah, I think the one aspect which is particular is that, given that fibroids comes after endometriosis for elagolix, that is a benefit for fibroids. If you -- the market preparation in terms of access, payer coverage, et cetera, all have been taken care of for endometriosis. So that will -- that kind of hurdle will be kind of out of the way when they launch fibroids -- at least, it can be accelerated. So I think I fully agree with the comments that Ernest made in terms of the dynamics from an unmet need perspective to these two diseases. From a practical operational perspective, that might be compensated by the fact that it's seconds and as such has a way -- a path for itself already laid out.
Mark Connolly -- Credit Suisse -- Analyst
Perfect. And then my second question is, with respect to the linzagolix endometriosis Phase III trials, can you compare the design of these two trials to the Phase II trial and then are there any differences in terms of baseline characteristics or how the actual endpoints are defined? Thank you.
Ernest Loumaye -- Chief Executive Officer
Yes. The population is essentially well the same, and you remember that our Phase IIb patient population match very well, what the elagolix population was. So we are really targeting moderate-to-severe endometriosis. The dose are either placebo, 75 milligram without add-back, and 200 milligram plus add-back. And in term of primary endpoint, you remember that the Phase IIb was, one primary endpoint which was global pain, including numbness during menstrual, obviously we got secondary menstrual and non-menstrual. But this time it's a co-primary endpoint, each having to meet statistical significance for achieving the success of the trial. So essentially similar population, two co-primary endpoints and well-defined dose for confirmation, 75 without and 200 with.
Mark Connolly -- Credit Suisse -- Analyst
Perfect. Thanks for taking my questions.
Operator
Thank you. Our next question comes from Liana Moussatos from Wedbush Securities. Your line is open.
Vasiliana Moussatos -- Wedbush Securities -- Analyst
Thank you for taking my questions. I have two on nolasiban. You mentioned that you're waiting for agreement with the FDA on trial design. Have you had the meeting and you're waiting for minutes or are you still waiting to have a meeting with the FDA? And then, my second question is, what are your plans for nolasiban in China?
Ernest Loumaye -- Chief Executive Officer
The first one, as we keep saying, dialog is ongoing with the FDA, and we are committed to report by end of June. The China, I think, is something we are very active here. We have different options on the table and the objective is really to carve out partnership by the end of the year, either with an international company or a local company or develop a joint venture. All options are on the table, but I can tell you that things are progressing. And so far, we are confident that we'd deliver, by end of the year, an agreement for the development of nolasiban in China. We are also actively interacting with IVF centers and preparing an IND by translating all the document necessary. So we are ready to move forward as soon as everything is defined.
Vasiliana Moussatos -- Wedbush Securities -- Analyst
Thank you.
Operator
Thank you. Our next question comes from Do Kim from BMO Capital Markets. Your line is open.
Do Guyn Kim -- BMO Capital Markets -- Analyst
Hi, thanks for taking my questions. A couple on linzagolix, in the long-term data for NOIs (inaudible). The patients who didn't enter the extension portion, do you think that the high responder rate you saw after 12 weeks is a real sustained effect or -- and do you know what potential underlying mechanism for that would be?
Ernest Loumaye -- Chief Executive Officer
Yes, I truly believe -- I truly believe this is a true carryover effect, maintenance effect. But the level of maintenance in the -- that we have is very high, but we have to acknowledge also there is very small number of patients. So therefore, we don't have yet the final. I think there a real mechanism of action, because the endometriosis is painful by inducing inflammatory reaction around the lesions on the peritoneum, which is then triggering nerve reaction and pain. And therefore, by cooling down the lesion for six months, we are not surprised that indeed it may be maintained -- the effect may be maintained for months, and the other very nice observation is that for those patients who are losing minimal amount of bone, but still some amount of bone, because we have minus 1% for the 75 and minus 2.2%, if I remember well, for higher dose, they really recover and there is an increase in bone mineral density, which on the small number exceed the baseline level. So I think this is a true physiological effect or a true pharmacological effect, I would say of the product. And that bring another interesting question is that -- often we have the question -- you start treating a patient at 31, do you think she is going to take for 19 years the drug up to menopause? We don't believe so. We believe that in the future, there will be more treatment than drug holiday for all the reason and then treatment again. And I think this system effect is really promising for this class of drugs.
Do Guyn Kim -- BMO Capital Markets -- Analyst
Great, thank you. And a question on the Phase III study in endometriosis. For the co-primary endpoints, how do you define a responder and is it the same way that elagolix co-primary endpoints responder was defined? And would you caution on making direct comparisons after the data?
Ernest Loumaye -- Chief Executive Officer
No, no, it is essentially the same. We had extensive -- really extensive discussion with the Patient-Reported Outcome division at the FDA and indeed the methodology is well defined. You remember that we have validated our pain questionnaire during the Phase II and it's going to be essentially a responder-based analyses based on a definition of reduction of pain, which is translating into a reduction of -- an improvement of patient well-being. So this is relatively complex, but well codified, well defined and we are fully aligned with the FDA in terms of what would we expect for the Phase III.
Do Guyn Kim -- BMO Capital Markets -- Analyst
Fantastic, and congrats on the progress.
Ernest Loumaye -- Chief Executive Officer
Yeah, thank you.
Operator
Thank you. Our next question comes from Eric Joseph from JPMorgan. Your line is open.
Eric Joseph -- JP Morgan -- Analyst
Hey guys. Congrats on the progress this quarter and thanks for taking the questions. I just had a question and follow-up of the --the long-term follow-up from EDELWEISS and where it would seem like on safety your -- it seems like there's a plateauing effect on bone loss at the 75-milligram dose looking beyond six months.I guess, would it be fair to interpret that data in that way? I'm wondering if you could comment on the confidence intervals of bone loss after 52 weeks and whether you're kind of within that lower bound limit of 2.3%. Also, whether you could just sort of comment on additional bone loss data looking at the (inaudible) or a hip scan? Thanks.
Ernest Loumaye -- Chief Executive Officer
Yes. So, the data we released shows that at three months, we had 0.8% and we had 1% at six months -- I'm sorry six months and 12 months, so 0.8% and 1%. Whether this difference is significant, we cannot know. But it's clear that we have not been losing an additional 0.8% over the next six months. So you're right that there is a tendency to plateau, to flat.We are still within the confidence interval of the critical zone for -- considering that there is a significant bone loss for the 75 milligram. What was interesting also is that the 200 milligram result add-back after six months where rerandomized to 100 milligram and then, we'll see that the bone loss tend to be slightly lower despite continuation of suppression. So it's quite sensitive to the dose. So to summarize, yes there is probably a plateau effect. Are we really at the bottom of the plateau? I think that we would see beyond 52 weeks if it goes good. And as we are still within the confidence interval and as I mentioned when we stop, it's amazing to see how bone rebuilds quickly.
Eric Joseph -- JP Morgan -- Analyst
Great. Great. And on -- a follow-up here on OBE022. Just how should we be thinking about the registration pathway in preterm labor and whether you anticipate different regulatory requirements between the EU and US as well as whether the data generated by the Phase IIa ongoing would be something you'd look to seek input from the regulatory bodies? Thanks.
Ernest Loumaye -- Chief Executive Officer
Yeah. Well, clearly, Eric, this is work-in-progress and we have no definitive answer to that. We -- at the end of this trial -- the program that we associate with an registered authority here in Europe, this was really to give the opportunity to first have the drug without having to put patient under pure placebo. But as we would be gaining efficacy data showing that indeed, we are well prophylactic that will be an important decision, whether we continue to develop it as a synergistic compound with atosiban or self-standing compound.
And I think it's really too early to say that. And that may have a big impact on how we develop it in Europe, but also in US, because as you mentioned already atosiban is not to our label in the US.
So I would say step-by-step, it's such an unmet need, such an important compound that we need to take the time to deliver well. And when we will read out PROLONG, I think we need to have a discussion together and see what would be the path forward. And we need definitively at that time to also consult the authorities to help us finding the most efficient path forward.
Eric Joseph -- JP Morgan -- Analyst
Thanks, that's helpful. Thanks for taking the question.
Operator
Thank you. (Operator Instructions) And our next question comes from Raghuram Selvaraju from H.C. Wainwright. Your line is open.
Edward Marks -- H.C. Wainwright & Co. -- Analyst
Hello, this is Edward Marks on for Ram. Just a few questions on the EDELWEISS trials. We've been talking about the endpoints here, and I'm just wondering if either of the co-primaries carry any more weight or if they're equally weighted? And then whether or -- what the significance of the dyspareunia end point is for the EDELWEISS study population?
Ernest Loumaye -- Chief Executive Officer
I mean both carry the same weight. To be successful, you need to have a p-value of less than 0.05 in each one. So I think that that's the point. Now non-menstrual pain is a little bit more difficult to control than menstrual pain. So in menstrual pain, if you reduce blood flow, you reduce the pain. We were extremely pleased to see in the EDELWEISS trial that indeed in the menstrual pain -- efficacy on non-menstrual pain was very good, especially when you continue to treat these patients beyond three months.If you ask patient, we had a brief survey in United States asking what are the most three bothering symptoms for you -- patient with endometriosis. First one is consistent abdominal pain. The second one is dyspareunia, and the third one is dyschezia.
So I think it's important -- we scored extremely well with dyschezia on Phase II. We scored well on dyspareunia. It was significant, if you remember well, with the high dose, it was not significant, but nicely improved with the -- not statistically significant with the 75, but there was a nice effect on it.So let's see the Phase III because the fact that we were not significant may just be a question of sample size. It would be fantastic to have both dyschezia and dyspareunia result with the low dose for the reason that we mentioned also because we know that for example, elagolix did not reach a significance on dyspareunia at the low dose and is using the high dose to control the dyspareunia. So the jury is still out, let's wait. But the Phase II data we're going in the right direction, but clearly we need now to confirm that in Phase III.
Edward Marks -- H.C. Wainwright & Co. -- Analyst
Thank you. And just a couple of more. I'm wondering what the powering assumptions were that went into the design of this trial and what sized signal might need to be observed for some of these studies to hit statistical significance? And also, how is consumption of some of the pain medication going to be monitored for EDELWEISS 2 and 3 with -- particularly about the opioids?
Ernest Loumaye -- Chief Executive Officer
Jean-Pierre, do you want to enter study power and medication?
Jean-Pierre Gotteland -- Chief Scientific Officer and Head of R&D
So for the co-primary endpoint, we've got 95% to detect a 40% response for the active versus 20% for the placebo, and this is the use of analgesics and especially opioids actually will be recorded. Of course, it's also been taken into account into the -- the way we are assessing the clinical meaningful response.
Edward Marks -- H.C. Wainwright & Co. -- Analyst
Thank you. And one final one. If I may, just on a broader level. Just wondering what's some of the notable similarities and differences are between the EDELWEISS trials and the SPIRIT trials for relugolix, also for endometriosis?
Ernest Loumaye -- Chief Executive Officer
First of all, there is only one dose, high-dose for suppression add-back therapy for everybody. So there is no data, no opportunity with moderate dose and no add-back and that's a major difference. Otherwise, it's both single oral dose. Jean-Pierre, you remember it? Their six months treatment, we go for 12 months treatment?
Jean-Pierre Gotteland -- Chief Scientific Officer and Head of R&D
We have basically the same design, it's six months of treatment and then an extension. So six months placebo-controlled study, then extension randomized but to the -- in our case, 75 milligram and 200 milligram plus add-back whereas Myovant, they do a 40 milligram plus add-back for the six months placebo control and then extension study up to 12 months and then six months of post treatment follow-up.
Ernest Loumaye -- Chief Executive Officer
So, the key differentiation is that they will not offer the non-add-back option.
Edward Marks -- H.C. Wainwright & Co. -- Analyst
Yeah, I could see that being important. Well, thank you for the details, and I appreciate you taking the questions.
Ernest Loumaye -- Chief Executive Officer
Thank you.
Operator
Thank you. And I am showing no further questions from our phone lines. I now like to turn the conference back over to Ernest Loumaye for any closing remarks.
Ernest Loumaye -- Chief Executive Officer
So, as usually, I want to thank you again for taking the time to join this call. I hope you are feeling that we're extremely excited about the progress we saw in our product pipeline, which is dedicated to improving the life of women and their families who suffer from devastating and life-altering condition. So we'll continue our development, and we look forward to updating you on our progress during our next quarterly call. Thank you everybody. Have a good day.
Operator
Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program.You may all disconnect. Everyone have a wonderful day.
Duration: 48 minutes
Call participants:
Mario Corso -- Senior Director, Investor Relations
Ernest Loumaye -- Chief Executive Officer
Wim Souverijns -- Chief Commercial Officer
Tim Adams -- Chief Financial Officer
Justin Burns -- RBC Capital Markets -- Analyst
Xiaozhou Fan -- SVB Leerink -- Analyst
Mark Connolly -- Credit Suisse -- Analyst
Vasiliana Moussatos -- Wedbush Securities -- Analyst
Do Guyn Kim -- BMO Capital Markets -- Analyst
Eric Joseph -- JP Morgan -- Analyst
Edward Marks -- H.C. Wainwright & Co. -- Analyst
Jean-Pierre Gotteland -- Chief Scientific Officer and Head of R&D
