With the annual American Association for the Study of Liver Disease (AASLD) meeting coming up next month, highly anticipated data readouts from the handful of companies developing all-oral, interferon-free hepatitis C regimens will take centre stage.
As expected, Gilead Sciences' Sovaldi (sofosbuvir) has taken over the rapidly evolving HCV market, making first-generation direct-acting antivirals like Vertex Pharmaceuticals' Incivek (telaprevir) and Victrelis (boceprevir) from Merck & Co. all but obsolete, while racking up almost $6 billion in sales since being launched late last year. In fact, Wells Fargo analyst Brian Abrahams estimates that as many as 98 percent of new patient starts were on a Sovaldi-containing regimen as of August.
The drug is indicated for use as part of a 12-week regimen with pegylated interferon and ribavirin for genotype 1 patients and a 12- or 24-week regimen with ribavirin in genotype 2/3 patients, but is increasingly being used off-label as part of a regimen with the next-generation protease inhibitor Olysio (simeprevir) from Johnson & Johnson, noted UBS analyst Matthew Roden.
But despite achieving cure rates above 90 percent while requiring shorter courses of therapy, available regimens are far from perfect, a fact not lost on AbbVie (partnered with Enanta Pharmaceuticals), Merck, Bristol-Myers Squibb and Achillion Pharmaceuticals (as well as perhaps Alios BioPharma, which is being bought by Johnson & Johnson), which are racing to bring all-oral combinations of their own to market in hopes of grabbing a piece of the rapidly expanding multi-billion dollar pie.
"For most companies, the strategy is not to topple Gilead from the leadership position, but rather to gain a reasonable share of the estimated $180 billion cumulative global market opportunity in the next 15 to 20 years," according to Edison analyst Jason Zhang.
Not content to rest on its laurels, Gilead is also working on new Sovaldi-based combinations of its own in the hopes of remaining the market leader for years to come. Experts believe new one-tablet, once-a-day regimens could eventually emerge offering cure rates along the same lines as what is out there now with as little as four weeks of therapy.
Rather than work together to achieve this goal, however, companies are focused on developing combinations made exclusively from in-house compounds given the obvious commercial advantages of doing so, such as the ability to co-formulate agents, maintaining a high degree of price flexibility and not having to share the financial upside with a competitor.
Bank of America Merrill Lynch analyst Colin Bristow noted that "next-gen regimens will likely combine three classes of therapy (nuc + NS5a + protease inhibitor) to achieve 90-plus percent SVR rates across genotypes with 4 to 6 week treatment durations," with Gilead and Merck currently in the best position given their respective nucs either on the market (Sovaldi) or in clinical development (Merck's IDX21437, for which it recently bought Idenix).
Below is a list of regimens in mid- to late-stage clinical development, along with those on the market. In addition to those included, Zhang noted that companies such as Alios/Johnson & Johnson and Enanta may also have the compounds needed to pursue all-oral, interferon-free regimens based exclusively on in-house programmes, though they have yet to publicly reveal an intent to do so.
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