Event – Hep C advances await panel votes

Analysis

Hepatitis C patients are on the verge of taking the next incremental step in therapy. Two competing pills, sofosbuvir from Gilead Sciences and simeprevir from Johnson & Johnson, will be before an FDA advisory committee at the end of October, with the promise of delivering new options for patients that have so far been left behind in the antiviral evolution.

Neither is the single-pill interferon-free regimen that is said to be anxiously awaited by perhaps millions of chronically infected patients, but each represents a significant step forward. Both agents are expected to take a significant role in multidrug cocktails as treatment protocols develop further, and many more patients stand to benefit should regulators wave them through.

Company   Johnson & Johnson Medivir Gilead Sciences
Product   simeprevir (TMC-435) sofosbuvir
Market cap   $246bn $457m $96.5bn
Product NPV   $928m $1.02bn $24.5bn
% of market cap   0% 223% 25%
Event type   FDA advisory committee FDA advisory committee
Date   October 24 October 25

Simeprevir's time to shine

While the FDA is undergoing a partial shutdown because of the US government funding impasse, limited user-fee funded activities are still underway. The Endocrinologic and Metabolic Drugs Advisory Committee meeting to consider an expansion in the label for Amarin’s Vascepa is still scheduled to occur later this week; so far there has been no indication that the antiviral committee meeting will be postponed.

Johnson & Johnson and Medivir’s simeprevir is set to be first up before the antiviral panel. Under its current application the protease inhibitor is intended to be used in combination with interferon and ribavirin in patients carrying genotype 1 of the hep C virus.

In terms of advantage over the protease inhibitors Incivek and Victrelis that premiered in 2011, simeprevir offers once-daily dosing to the three times daily of the previous generation. Those drugs, in turn, offered an advantage over the interferon-ribavirin dosing alone in that they demonstrated better cure rates as well as allowing some patients a shorter overall treatment duration.

Interferon and its flu-like symptoms and central nervous system side effects have been seen as a barrier to treatment for many patients, so reducing or eliminating reliance on it has been a goal of many specialists.

The Quest-1 and 2 trials showed that simeprevir could improve on the viral cure rates of interferon and ribavirin alone in patients who had never been treated before, while the Promise trial did the same for patients who had relapsed after previous treatment.

Approval in this first indication will be an important step forward in ensuring that simeprevir will be included in the emerging drug combinations now in advanced clinical trials. Phase II trials in combination with Idenix Pharmaceuticals’ NS5A inhibitor samatasvir and ribavirin, and in combination with Bristol-Myers Squibb’s daclatasvir with and without ribavirin, are expected to report data before the end of the year.

Importantly, the trial with samatasvir includes patients with genotype 4 of hepatitis C, and this trial would be important to confirming its efficacy outside of genotype 1, the most common strain in North America but less predominant elsewhere.

Pan-genotype efficacy

On the other hand, Gilead’s sofosbuvir, the NS5B inhibitor it scooped up with the $11bn acquisition of Pharmasset, has already demonstrated efficacy in multiple strains of hep C. The FDA panel will be voting whether to support approval in genotypes 1 through 6 in combination with “other agents”.

In phase III trials it showed efficacy with interferon and ribavirin in never-treated hep C patients with genotypes 1, 4, 5, and 6, and with ribavirin alone in genotype 2 and 3 patients in patients who have never been treated, those who have, and those unable to take interferon.

Given that they are on a similar approval timetable – simeprevir has an action date of November 28 and sofosbuvir December 6 – analysts from RBC Capital Markets raised the possibility that a broad label for sofosbuvir could allow off-label use with simeprevir, particularly in genotypes 2 and 3 where an all-oral combination has already been effective.

Should the advisory committee and the agency back it, sofosbuvir will be one of the most closely watched launches of 2013. The EvaluatePharma  forecasts for sofo, and the all-oral single-dose combination with ledipasvir, are now at $9.24bn in 2018, accounting for more than one-third of the value of even a big biotech company like Gilead.

Given that the acquisition of Pharmasset is now considered one of the triggers of the biotech bubble, any stumble at this point might not be taken well by investors throughout the sector. Thus, anything short of a flawless panel debate will be received poorly.

To contact the writer of this story email Jonathan Gardner in London at jonathang@epvantage.com or follow @JonEPVantage on Twitter

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