Friday, April 20, 2012

Have BMS and Gilead found the 'killer app' for hep. C?

Have BMS and Gilead found the 'killer app' for hep. C?
Bristol-Myers Squibb and Gilead said this morning that an all-oral therapy joining together two drugs the companies are each developing suppressed the virus in more than 95% of patients across a broad spectrum of genotypes.

The drug combo of daclatasvir from BMS and Gilead's GS-7977 reached a 100% sustained virologic response (SVR), or cure rate, at week four in one common subgroup, genotype 1 patients who have not been previously treated with interferon—an injectable associated with flu-like side effects.

The 100% cure rate held even when ribavirin, another traditional mainstay of treatment, was left out of the mix, bettering a roughly 90% SVR rate seen for an Abbott triple therapy in a trial a few weeks ago.

“It obviously doesn't get any better than this,” cheered ISI analyst Mark Schoenebaum in a quick note to investors this morning after BMS and Gilead announced their results. Data from the Phase II combo trial are “best case,” he added, in that only 2% of respondents to an informal survey he fielded earlier this month said they expected the 100% SVR rate.

The findings accelerated momentum in an already fast-moving category, in which drugmakers are swooping up assets to pad HCV pipelines and experimenting with a variety of regimens and combinations. Last November Gilead agreed to pay almost $11 billion for biotech firm Pharmasset's GS-7977, and BMS in January said it was buying Inhibitex for about $2.5 billion and getting access to that firm's potential HCV drug, INX-189.

The direct-acting antivirals (DAAs) from BMS, Gilead and Abbott are showing the best efficacy and tolerability to date.

Not that there haven't been speed bumps along the way. In February, Gilead's ‘7977 had come under assault when data showed that six out of six subjects treated with the pipeline drug, who were prior null responders to other HCV therapy, had experienced a relapse of their disease.

Analysts had predicted that patients who are na├»ve to therapy would be easier to treat with a non-interferon regimen than null responders, and the Gilead/BMS data furthered this notion. Several analysts now believe daclatasvir, an NS5a inhibitor, and ‘7977, a nucleotide analog (or “Nuc” as the class is called), may form the best treatment “backbone” option across all genotypes.

“It appears that the ‘killer app' in HCV is probably an NS5A plus a nuc without ribavirin,” Schoenebaum declared.

The newer protease inhibitors—Vertex's Incivek and Merck's Victrelis, both launched in 2011—look like they will be vulnerable to the all-oral regimens, but not for a few years.

“These results obviously reinforce the expectation that DAA-only (IFN and RBV-sparing) regimens will likely quickly supplant current HCV treatments when they become available in the 2015/2016 timeframe,” wrote Deutsche Bank's Barbara Ryan in a note today.

In a Thursday dispatch to investors, Credit Suisse's Catherine Arnold said the data also “takes a little shine off” Abbott's HCV program, “but we still view it as a competitive presence.” The triple therapy combines the firm's protease inhibitor ABT-450 + non-nucleoside polymerase inhibitor ABT-333 + ribavirin.

While the Gilead/BMS combination sets the bar high for competitors, scientists are still debating where the best treatment synergy lies, and firms are awaiting more data before finalizing their commercial plans.

The Gilead/BMS combo “represents the most compelling all-oral, interferon-free data in the highly visible [HCV] marketplace,” noted Arnold. “Despite this strong data,” she added, “a partnership is unlikely in the near term as both companies wait for additional data sets related to their HCV assets to fully evaluate their options.”

Ryan cautioned that other factors—side effects, dosing convenience and, of course, cost—“will be important considerations in determining market share. In our opinion, it is premature to conclude who the ultimate winners and losers will be in the ‘new' HCV market on the basis of the data available to date.” Ryan doesn't think any one or two players will dominate the field. Null and non-responders could also be a factor in determining long-term HCV dominance.

Results from a cocktail joining Gilead's ‘7977 and ribavirin also surprised, hitting an SVR rate of 88%—far better than the 50% the Street had expected, according to Schoenebaum. Abbott's all-oral triple combo may be another good backbone option, while daclatasvir so far looks like a solid add-on option—one that has pan-genotype efficacy and excellent tolerability—and BMS is exploring multiple pairing options (including with its own Nuc, INX-189).

Other Nucs in development include Vertex's ALS-2200 and ALS-2158, and biotech firm Idenix's IDX184, which can be combined with its NS5A inhibitor, IDX719.


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