Alnylam (ALNY -0.28%) shares jumped this week after reporting that it would actively advance an RNAi program for the treatment of chronic hepatitis B.
Up to 400 million people suffer from chronic hepatitis B worldwide and, currently, there's no cure. The sheer size of the patient population and the significant need for better treatment options have caught the attention of drug developers eager to address this important market.
However, Alnylam's new program could be years from commercialization, suggesting investors may be better served focusing on late-stage programs under development at Gilead (GILD 0.23%) instead.
First, a bit of background
Two of the most commonly used treatments for hepatitis B are Bristol-Myers' Baraclude and Gilead's Viread. Both are used to reduce the virus' presence in patients, and to curb the virus' ability to replicate.
Baraclude, which won FDA approval in 2005, has been used in more than 400,000 patients since its launch, and racked up more than $1.5 billion in sales last year for Bristol, up 10% from 2012. Baraclude's sales momentum continued into the first quarter, with Bristol reporting sales of the drug rising 11% year over year, to $406 million.
Viread, which is approved for use in HIV and hepatitis B patients, is also a top seller. Viread's sales totaled $950 million in 2013, up 13% from 2012, and reached $210 million in the first quarter.
However, despite Baraclude and Viread's commercial success, there remains significant room for improvement. Roughly 600,000 people still die from the effects of chronic hepatitis B due to liver failure or liver cancer each year. Most of those deaths occur in developing markets, including Africa and East Asia, where the disease is most prevalent and vaccines are less common; however, the disease is found everywhere. For example, up to 1% of Europeans and Americans are chronically infected with the disease.
Promising new treatments
Given the significant need for new therapies, it's understandable that investors got excited about Alnylam's plans to advance ALN-HBV, a drug that was acquired when Alnylam purchased Merck's RNAi assets in January. However, before investors get too far ahead of themselves, it's important to remember that ALN-HBV is a pre-clinical drug.
Alnylam hasn't filed an IND for ALN-HBV yet (the first step in taking a drug from the lab to human patients), and doesn't think it will file it until late next year. Once the drug moves into human trials, there's also no guarantee that it will make it to market. Roughly 90% of drugs in phase 1 trials fail to make it to the FDA for approval, with the majority -- some 60% -- failing during phase 2. And even if the drug makes it through phase 3 and gets in front of the FDA, there's no guarantee the agency will approve it.
Dynavax successfully demonstrated that its hepatitis B vaccine, Heplisav, outperformed GlaxoSmithKline's hepatitis B vaccine Engerix-B during trials; however, both the FDA and European regulators nixed approval over concerns tied to the study's ability to detect rare, but serious, side effects. As a result, Dynavax has been forced to begin another costly phase 3 trial to quell concerns, data for which isn't expected until late in 2015.
Closer to realization
Since Alnylam's potential hepatitis B treatment is years away, investors may want to concentrate on compounds closer to market, including Gilead's tenofovir alafenamide, a drug being studied as a treatment for both HIV and hepatitis B.
Tenofovir alafenamide is a novel formulation of Gilead's Viread, and the new tenofovir formulation showed similar efficacy to Viread in phase 1b trials with fewer side effects -- particularly relating to kidney function. Gilead has since advanced the drug into phase 3, with an estimated primary completion date of November 2015.
Beyond tenofovir alafenamide, Gilead is also working on GS-4774 and GS-9620, which are in phase 2 and phase 1 trials, respectively. Data from the GS-4774's phase 2 trial should be reported in six to 12 months.
Fool-worthy final thoughts
There's no question that hepatitis B is a significant disease that requires new, innovative therapies. Alnylam's ALN-HBV program could prove wildly successful, or it may end up on the cutting room floor. It's just too early to know for sure. That risk suggests that investors should keep an eye on Alnylam's program, but may find that Gilead's hepatitis B program makes for a better investment, particularly in light of Gilead's proven success in treating hepatitis B, HIV, and hepatitis C.
