AASLD – Gilead hits new high with a little help from its friends

Gilead Sciences needed the help of Bristol-Myers Squibb after all to live up to investor hopes of a one-pill, once-a-day, interferon-free regimen in hepatitis C. The New York group released data from a trial of its antiviral daclatasvir with Gilead’s sofosbuvir that has gone a long way to confirming the efficacy of the California group’s wholly owned late-stage combination.

Gilead shares breached the $70 barrier for the first time on the news, rising 14% to $73.93 Monday driven by a notable late-day boost once the data were unveiled at the AASLD liver meeting in Boston. The almost complete viral suppression following a 12-week regimen built confidence that Gilead had indeed come up with a pill dubbed “perfectivir” that can do away not only with interferon but also with its sidekick ribavirin.

“Up until very recently ribavirin has played a critical role in hepatitis C treatment regimens,” said Dr Mark Sulkowski, a Johns Hopkins University professor and medical director of its viral hepatitis centre. “It was initially surprising and also encouraging that this combination may not require ribavirin, which has of course has side effects along with teratogenicity.”

A helping hand

It may seem counterintuitive that a Bristol-Myers trial may benefit its competitor. However, in this study daclatasvir was viewed as a stand-in for Gilead’s own GS-5885; both are hep C non-nucleoside NS5b inhibitors.

Gilead has had some success testing a two-drug combination – sofosbuvir, the nucleoside NS5b inhibitor also known as GS-7977, plus ‘5885 – but so far much of the data has been with ribavirin, for longer treatment durations and in the easier-to-treat hep C genotypes 2 and 3. The daclatasvir-sofosbuvir trial has been the first time a nucleoside/non-nucleoside-only combination has shown efficacy in the tough and much larger genotype 1 population for a 12-week treatment duration.

Analysts said the trial was the best-case scenario, with 98% of patients showing complete viral suppression four weeks after the finish of a 12-week treatment schedule. Bullish UBS analysts declared, “Say goodbye to ribavirin.”

Much of the focus in hepatitis has been on eliminating interferon, as it has psychiatric and flu-like side effects that are a major barrier to treatment. However, ribavirin carries a black box warning for haemolytic anaemia that can lead to a worsening of cardiovascular disease, along with the warnings of birth defects; thus a direct-acting antiviral with fewer side effects would be welcomed by patients and physicians.

The news surely has Bristol-Myers ruing the day that Gilead decided to go its own way – a decision that might have been surprising, given their past collaboration on Atripla, were it not for the California group’s need to squeeze maximum value from its $11bn purchase of Pharmasset (EASL – Gilead-BMS score all-oral hep C win but will pairing last?, April 19, 2012).

With $5.78bn in forecast sales in 2018, according to EvaluatePharma’s consensus forecast, GS-7977’s net present value now stands at $21.5bn, so it is understandable that Gilead is not in a sharing mood. These numbers will probably move upward with additional good news.

Long shadow

The news completely overshadowed impressive data from interferon-free combinations from Bristol-Myers and Abbott. In Bristol-Myers’ case it is a three-drug combination of daclatasvir, asunaprevir and BMS-791325, which achieved 94% viral suppression 12 weeks after the end of a 12-week treatment course. One of the 16 patients in that arm was lost to follow-up, but when tracked down 24 weeks after ending treatment was also determined to have undetectable virus load.

Abbott also outlined previously released positive data from its more complicated regimen of ritonavir boosted protease inhibitor ABT-450 with nucleoside NS5b inhibitor ABT-267, non-nuc ABT-333 and ribavirin, which achieved a 99% viral suppression rate 12 weeks after finishing a 12-week course of treatment in previously untreated patients, 93% in patients who have not responded to previous treatments.

Previously untreated genotype 1b patients had a 100% response rate, suggesting they may be good candidates for ribavirin-sparing regimens, said Dr Kris Kowdley, a hepatologist at Virginia Mason Hospital in Seattle.

The Abbott combination has the potential to make it to market first in the genotype 1 population. However, its growth could be limited by its complicated dosing regimen should the Gilead product prove itself. Dr Kowdley told attendees that a tablet combining ‘450 and ‘267 will be used in phase III trials.

Meanwhile, Gilead expects to have interim data from its first all-oral phase III in the genotype 1 population early in 2013, although it has not stated whether it expects to release the data publicly. ISI Group analyst Mark Schoenebaum says if the group does not release the interim data revisions to that study or the launch of a second phase III study could be a clue that the results are good.

Signs of positive data would be dropping any arm with ribavirin or a 24-week treatment regimen and pursuing 12-week treatment with sofosbuvir and ‘5885 alone, Mr Schoenebaum said.

It did not seem possible for expectations for sofosbuvir to be greater than they already were, but data at AASLD seem to have only inflated them. Gilead needs it to keep coming through to sustain its record share prices.

Study Trial ID
Sofosbuvir + daclatasvir NCT01359644 
Daclatasvir + asunaprevir + BMS-791325 NCT01455090
ABT-450 NCT01464827

To contact the writer of this story email Jonathan Gardner in Boston at jonathang@epvantage.com

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