It was a remarkable year for the biotech sector. The NASDAQ Biotechnology Index soared more than 65% as investors witnessed a slew of new drug approvals, multibillion-dollar acquisitions and close to 40 IPOs. Looking beyond this broad overview, however, there were a number of specific surprises -- some good, some bad -- for both investors and patients.
To get more insight into this complex industry, we asked our top analysts to reveal their thoughts on the most surprising biotech stories of 2013.
To me, nothing sums up 2013 greater than the rapid advancement we've witnessed in treating hepatitis-C.
This liver disease, which affects up to 3.2 million people in the U.S. and an estimated 180 million worldwide, had been treated with a combination of pegylated interferon and ribavirin for 24 to 48 weeks prior to May 2011, and delivered an average response in about 50% of patients.
This year, however, we saw the approval of Gilead Sciences (NASDAQ:GILD) Sovaldi by the Food and Drug Administration, as well as encouraging data from AbbVie (NYSE: ABBV) with its direct-acting antiviral combo drug, which were both able to deliver sustained virologic responses (an eradication of detectable levels of the disease) of 90% or greater in genotype 1 patients -- the most common but hardest to treat genotype.
Sovaldi's approval marks a "first" in treating hepatitis-C in that it's the first oral therapy for genotype 2 and 3 patients that isn't given in combination with interferon, which can cause flu-like symptoms in patients. Therefore, not only did this therapy improve SVR dramatically, but patient quality of life also took a huge leap forward. A more recent trial combining Sovladi with ledipasvir delivered an SVR of 94% in treatment-naïve genotype 1 patients without the need for a ribavirin in just eight weeks!
AbbVie's DAA combo has been equally exciting with an SVR after 12 weeks of 96% when given with a ribavirin in its latest late-stage trial.
This upcoming year could very well be the beginning of the end for hepatitis-C as a major worldwide-disease threat.
In October, Ariad said it was pausing and eventually stopping a clinical trial testing its leukemia drug, Iclusig, in the first-line setting because of the potential for blood clots. That wasn't particularly surprising given there were an unusually large number of blood clots in the pivotal trial used to gain FDA approval. A follow-up of those patients demonstrated it wasn't a fluke.
What surprised me was the Food and Drug Administration pulling Iclusig off the market while it figured out a population where the risks were worth the potential benefit. There were only 640 patients on the drug at the time; surely the agency could have figured out some other way to communicate the new information about potential side effects with doctors without pulling the drug from the market and making them go through special channels to acquire it.
Perhaps even more surprising is the speed at which the agency wrapped up its conclusions about who should get the drug, allowing Iclusig back on the market less than two months later. In retrospect, it shouldn't have been surprising since pulling the drug from the market seemed extreme, but if the agency was going to be that cautious to begin with, a long drawn-out process appeared inevitable.
Moral of the story: Never underestimate the perplexity of the FDA. Also be careful buying drugmakers with side effects in their pivotal trials that could come back and bite the company post-marketing. Despite being well off its 52-week low, Ariad Pharmaceuticals is nowhere near where it sat before this saga began.
Sarepta Therapeutics (NASDAQ:SRPT) entered 2013 riding major momentum. Its stock shot up nearly five-fold in 2012 on the strength of encouraging results from a midstage study of eteplirsen, which targets the treatment of the rare disease Duchenne muscular dystrophy, or DMD. Investors eagerly anticipated the prospects of an accelerated approval by the FDA, but they were sorely disappointed.
The FDA decided that Sarepta's application for the accelerated approval of eteplirsen was premature, and shares of the fledgling biotech crashed in November. Many of us who follow Sarepta were hopeful, but at the same time not entirely convinced that the FDA would be swayed by the company's phase 2 study data because of the small number of patients involved. The agency ultimately told Sarepta that it was too early to file its application for approval, and said that there was "considerable doubt" about using dystrophin expression as a predictor of clinical benefit. It used that "considerable doubt" phrase again in reference to the validity of the terrific results that Sarepta reported from the six-minute walk test in the midstage study. There really wasn't much good news at all with the FDA's response.
What started out as a promising year -- Sarepta's shares had doubled by mid-July -- ended up horribly: The stock fell nearly 60% on the day the FDA news was announced. Shares have mounted somewhat of a comeback since then, but the biotech's stock is still down around 24% for the year. Sarepta now faces a long couple of years or so as it moves forward with a phase 3 study of eteplirsen, and the stock will continue to be hotly debated by investors in the years to come.
Stephen D. Simpson:
There were plenty of notable events in the biotech world during 2013, but for me one of the most surprising stories is the building optimism for RNA interference, or RNAi, therapies and its leading developers Alnylam Pharmaceuticals (NASDAQ: ALNY) and Isis Pharmaceuticals (NASDAQ:IONS). This was not the first year in which these stocks outpeformed, but the good times have kept rolling; share of Alnylam have more than tripled in 2013, while Isis is up 280% year to date.
Investors should also realize that these stocks are not appreciating in a vacuum. Early stage data from Alnylam has put patisiran (formerly TTR02) and TTRsc on track as potential blockbusters for the treatment of familial amyloidic polyneuropathy and familial amyloidic cardiomyopathy, and the company now has four drugs in active clinical trials and one more that is quite close. For Isis, 2013 brought its first major drug approval (Kynamro, which is marketed by Sanofi and the company and now boasts over a dozen programs in active clinical development either in-house or with partners. Both of these stocks, and the development of new RNAi therapeutics, will continue to be exciting to watch in the year to come.
Any list of surprising biotech stories can't leave off Amarin (NASDAQ:AMRN), a stock with huge expectations heading into 2013. Its highly refined fish-oil drug Vascepa was approved for severe triglyceride levels in 2012, but the real money maker was always getting expanded approval to treat the larger patient population suffering from high triglycerides levels with mixed dyslipidemia. It's the difference between selling to 4 million patients versus 36 million patients.
To that end, Amarin did everything right, including getting an FDA SPA, essentially pre-agreed approval criteria, for its wildly successful ANCHOR trial. Unfortunately, fate intervened in the form of question marks over the efficacy of fish oil in preventing cardiovascular problems. Part of this skepticism was fueled by scientific journals challenging the link between lowering triglycerides and reducing heart problems. In light of these new studies, the FDA advisory panel voted 9-2 against expanded approval and the FDA agreed, going as far as revoking Vascepa's SPA. This is some serious goal-post moving by the FDA, but for investors it's another painful reminder the agency always has the last word.
So where does that leave investors? Shares collapsed over 75% this year, but Amarin isn't relegated to penny stock status. There is still a heartbeat here -- if faint. Vascepa remains an approved drug generating sales, even if investor expectations for this product have been dramatically lowered. And Amarin is appealing the FDA's decision, but victory is doubtful here, too. A large ongoing phase 3 trial called REDUCE-IT that can prove that Vascepa, when used in conjunction with a statin, leads to better cardiovascular outcomes is needed to jump-start growth -- if the results turn out to be positive, of course. This stock could become the biggest redemption story of 2016, but in the meantime investors are better served looking elsewhere.
Our Top Stock Pick for 2014
Fool contributors Sean Williams and Brian Orelli have no positions in any stocks mentioned. Keith Speights owns shares of Gilead Sciences, Stephen D. Simpson, CFA owns shares of Alnylam Pharmaceuticals, and David Williamson owns shares of AbbVie. and Amarin plc (ADR). The Motley Fool recommends Alnylam Pharmaceuticals, Gilead Sciences, and Isis Pharmaceuticals. Try any of our Foolish newsletter services free for 30 days. We Fools may not all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors. The Motley Fool has a disclosure policy.