The standard of care for Hepatitis C (HCV) radically changed when the first direct-acting antiviral agents hit the market two years ago. Prior to their approval, the standard of care consisted of painful interferon injections 3-5 times a week for up to 48 weeks. Worse still is the fact that only about 50% of patients are even responsive to interferon, and the injections tend to make patients feel like they have the flu throughout the course of treatment.
With such a high cost compared to the potential benefits of interferon treatments, researchers have been busy looking for new oral-based therapies that are interferon-free. Direct-acting antiviral agents have been the result of this effort. Presently, there are over 20 such agents under development, with two coming up for FDA review later this month.
Gilead (NASDAQ: GILD ) is seeking approval for its much anticipated sofosbuvir on October 25th, whereas Johnson & Johnson (NYSE: JNJ ) will present its approval case for the more niche-based simeprevir a day before. Abbvie (NYSE: ABBV ) and Bristol-Meyers Squibb (NYSE: BMY ) are also expected to file New Drug Applications for their own all-oral HCV concoctions next year.
Are Sofosbuvir and Simprevir interferon-free?
The short answer is well, yes and no—or perhaps, at least not yet. While these drugs have been billed as the next generation of HCV drugs, the truth is they are more like a stepping-stone towards truly all-oral therapies that are interferon-free.
Presently, simeprevir and sofosbuvir are both seeking approval as treatments for HCV genotype 1 taken alongside interferon injections. The major advancement is that patients show dramatically improved cure rates on these particular direct-acting antiviral agents—up to 95% in clinical trials for sofosbuvir.
That said, sofosbuvir is up for approval as an interferon-free treatment for the rarer forms of HVC, namely genotypes 2 or 3. Because genotype 1 is by far the most prevalent form of the disease worldwide, however, the ultimate goal is to develop interferon-free drugs for this particular indication.
What’s the next step towards this goal?
Abbvie, Bristol-Myers Squibb, and Gilead have all been burning the midnight oil testing different combos of their various interferon-free treatments in hopes of producing such a therapy. The good news is that the results have been, well, nothing short of amazing.
The interim results of the COSMOS study testing a combo of simeprevir and sofosbuvir, for example, showed greater than 90% cure rates. Another study looking at a combo of Gilead and Bristol-Myers Squib’s drugs resulted in a 100% cure rate. While it’s unclear if these drug combos will receive explicit FDA approval due to the enormous costs associated with running such trials, doctors could use these combos off-label once the individual drugs have been approved. Based on these promising results, I expect this will be the case.
Why are there so many companies racing to develop HCV therapies?
The long list of Big Pharma companies developing all-oral HCV is certainly impressive. Yet, it’s important to keep in mind that they are not undertaking this wildly expensive endeavor for humanitarian purposes only.
With a market size estimated at $20 billion already, there will probably be multiple all-oral based HCV therapies within the next decade, and more than one blockbuster among the group. Sofosbuvir, if approved, should see peak sales topping $6 billion. And even simprevir with its niche market as an indication for severe forms of HCV is likely going to generate sales over $600 million a year.
With both sofosbuvir and simprevir receiving Priority Review status from the FDA, it’s likely both drugs will be approved. Even so, the sheer size of the HCV market and the potential for combination treatments, suggests that front runner status won’t necessarily confer a strong competitive advantage. I expect doctors will experiment with these different drugs to find what works best in the real world. And only time will tell which of these new generation HCV therapies will get the lion’s share of the HCV market.