In a study among 41 patients of Gilead’s sofosbuvir with Bristol’s daclatasvir, with or without the generic antiviral ribavirin, 40 were virus-free 12 weeks after six months of treatment, according to results presented yesterday in Amsterdam. The other patient didn’t turn up to the last appointment and was later found to be virus-clear. All the patients had failed prior treatment with either Vertex Pharmaceuticals Inc. (VRTX)’s Incivek or Merck & Co. (MRK)’s Victrelis.
The lack of a late-stage study, and the expense of the pills, will probably put the Gilead-Bristol combination out of reach for doctors and patients, said Geoffrey Dusheiko, a professor of medicine at the Royal Free Hospital in London.
“It’s a conundrum for us,” Dusheiko said in an interview after the results were presented at the European Association For the Study of the Liver’s conference. “It looks a very promising regimen, it really does. But I’m really not sure it’ll see the light of day.”
Still, doctors may be tempted to prescribe the Gilead-Bristol combo “off-label” once both drugs are approved, said Mark Thursz, secretary-general of the European liver association.
“Lots of investigators around Europe and the U.S. are itching for the opportunity to put together what they believe to be the optimum combination for our patients,” Thursz said. “The only barrier to that is what is the combination cost going to be because I suspect there will be package deals to be had.”
The combination had previously demonstrated success in patients who hadn’t been treated before. Those who have failed Incivek or Victrelis are “perhaps the most difficult-to-treat population” and have no current options, said Mark Sulkowski, a doctor at Johns Hopkins University in Baltimore who presented the results.
Bristol-Myers, based in New York, was working on the combination with Pharmasset Inc., which developed sofosbuvir, when Gilead bought the company for $10.8 billion in 2011. Gilead subsequently focused on developing sofosbuvir in combination with its own drug, ledipasvir. That combination cured 100 percent of patients in a mid-stage patient study, and the company is testing it in two late-stage studies.
Gilead and Bristol have planned no further trials of the combo because Foster City, California-based Gilead is focusing on a cocktail that contains only its own drugs. “We believe that we have been able to advance the development of SOF (sofosbuvir)/ledipasvir much more quickly than would have been possible with any inter-company collaboration,” Gilead’s chief scientific officer Norbert Bischofberger said in an e-mail.
Bristol is “committed to driving advances in hepatitis C research both through internal development and external collaborations to study the best treatments” and is working with Johnson & Johnson (JNJ)’s Janssen unit to study daclatasvir with simeprevir, it said in an e-mail.
Still, while ledipasvir may be effective against patients with hepatitis C genotype 1, the most common form worldwide, it may not work for those with genotype 3, which accounts for about 25 percent of cases in Europe and 45 percent in the U.K., said Graham Cooke, a clinician at Imperial College London. Daclatasvir and sofosbuvir are both active in that group, he said.
“We probably have a better option for G3 that we could be using if the companies were cooperating,” Cooke said in an interview. “Daclatasvir and sofosbuvir looks much better but Gilead very clearly want to develop in-house.”
Prescribing the two drugs as an off-label combination may be too expensive because they’ll probably have high prices as individual therapies whereas Gilead’s cocktail may be cheaper, he said.
Off-label use may also be dangerous, said Jean-Michel Pawlotsky, a professor of medicine at the University of Paris-Est.
“We don’t have enough safety data,” Pawlotsky said in an interview. “If a doctor does that and there’s a major accident, the doctor is liable. It’s dangerous but I know that people will do it.”
Bristol-Myers agreed last week to study daclatasvir in combination with Merck’s MK-5172. This month it also agreed to test the drug together with Cambridge, Massachusetts-based Vertex’s VX-135.
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