BMS, Abbott HCV pill data suggest competition for Gilead

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Abbott and BMS peeled back the curtain on some impressive clinical trial results in advance of the American Association for the Study of Liver Diseases' annual meeting, taking place November 9-13. There, 7,000-8,000 clinicians, researchers and manufacturer representatives will descend on Boston's Hynes Convention Center to hear highly-anticipated data presentations as companies sprint to produce the first all-oral anti-HCV treatment regimen.

While the current HCV paradigm offers unprecedented cure rates, the patient and treatment community is eager to replace the current interferon-based regimens with all-oral therapies to improve the tolerability profile.

"Most patients with HCV will soon be cured with an all oral treatment," said Dr. Norman Gitlin, MD of Atlanta Gastroenterology Associates and Emory University. "The tremendous recent advances in the management of HCV have led us to believe that a highly effective all-oral treatment of 3 to 6 months duration is a year or two away."

Abbott Laboratories was the first to start whetting clinicians' and investors' palates with some impressive Phase IIb data from the AVIATOR trial on its investigational interferon-sparing anti-viral triad, which offered 99% of therapy-naive patients a “sustained virologic response” or “SVR” after 12 weeks. Not only that, but its triple drug recipe (comprised of ABT-450, ABT-267, and ABT-333) in conjunction with ribavirin, also posted unprecedented results in hard-to-treat “null responder” patients, with 93% of patients achieving SVR. With these findings under its belt, the regimen is now advancing to Phase III testing.

In an investor note yesterday, ISI Healthcare/Biotech & Pharma Analyst Dr. Mark Schoenebaum pointed out that while the results are in the most prevalent HCV genotype, genotype 1 (GT1), the 99% figure was produced from a pooled analysis, “[T]hus, we don't yet know the SVR rates in individual arms with different regimens.” Dr. Schoenebaum also cautioned that Abbott's regimen involves a relatively high pill burden and needs to be taken with ritonavir, a re-tasked protease inhibitor (PI) employed for its pharmacokinetic boosting properties. HIV-treating clinicians have mixed feelings about ritonavir because although it boosts the activity of other PIs, it produces gastrointestinal and metabolic side effects and requires the patient to take another pill.

While 99% sounds impressive and is comparable to other all-oral data in treatment-naïve patients, Dr. Schoenebaum regards the null responder data as most impressive because they best all of the data which Gilead has produced on its HCV NS5B RNA nucleotide polymerase inhibitor, Sofosbuvir (formerly GS-7977 and, prior to that, PSI-7977). Sofosbuvir is widely regarded as the most promising of the emerging crop of oral treatments for Hepatitis C.

In addition to the Abbott data, Bristol-Myers Squibb (BMS) offered an enticing preview of its all-oral combination of a protease inhibitor, an NS5A, and a non-nuc. These impressive results were an encouraging sign of rebirth after BMS' massive setback earlier this year with its $2.5 billion purchase of Inhibitex. Clinical development of Inhibitex' oral nucleotide polymerase inhibitor, INX-189, was halted due to cardiovascular toxicity even before the ink was dry on BMS' purchase agreement.

The BMS abstract, which also showed results on an interferon-free, ribavirin-free 12-week all-oral regimen that included Daclatasvir (an NS5A replication complex inhibitor), Asunaprevir (an NS3 protease inhibitor), and BMS-791325 (an NS5B Polymerase Inhibitor) yielded results of 94% in treatment-naïve patients with the most common HCV genotype, GT1. Remarkably, the regimen produced 100% SVR in patients genotype 1a patients. In a separate investor note released yesterday, Dr. Schoenebaum noted that, “[T]his is encouraging since suddenly [Bristol-Myers Squibb] is back in the efficacy game.” At the same time, he illuminated some potential headwinds that BMS' regimen will face including twice-daily dosing, PI-related GI tolerability issues, and potential evidence of liver toxicity. From a commercial perspective, he also mentioned that BMS is 1-2 years behind Gilead in time to market.

In light of the ABT and BMY coming attractions, the health care equities department at Credit Suisse were quick to point out that these studies show early signs that a nuc-free regimen is a viable therapeutic strategy. Until now, as they write, “[M]uch has been made previously about the value of a nucleotide (nuc) in a HCV regimen, with [Gilead] being viewed as a winner in a supposedly ‘take-all' HCV marketplace. ABT and BMY's data release today suggests that the advantage of using a nuc may not as meaningful as previously thought.” Further, “These additional datasets reaffirm our view that the HCV space is not likely to be a winner takes all market, but will have multiple credible competitors.”

The Abbott regimen also drives competitive pressures on Gilead because they showed impressive results (89-92%) with just 8 weeks of therapy (versus 12 weeks for Sofosbuvir).

Nonetheless, both Credit Suisse and ISI's Schoenebaum concur that Gilead is leading the pack towards developing the first all-oral regimen. Credit Suisse analysts estimate that Gilead's regimen will produce around $3.8BN in 2020, with Abbott's franchise at around $2.5BN and BMS' at around $1.3BN. The data released today up the ante on Gilead's nuc/NS5A combination, which also will be presented at AASLD, to deliver SVR rates at least in the 90-95% range in GT1 patients.

Noah Pines is president of Gen., LLC a global marketing research and consulting agency offering strategic and tactical services to biopharmaceutical companies. He does not currently consult for any of the companies mentioned in this article
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