Ariad Pharmaceuticals CEO Harvey Berger has been fielding questions from investors for months about how much toxicity his company’s experimental cancer drug might be causing to the pancreas. The final verdict isn’t in yet, but an interim analysis being released today suggests the drug is safer than most thought it would be.
The preliminary results come from a pivotal study known as PACE, which is projected to enroll 450 leukemia patients on ponatinib, a drug candidate from Cambridge, MA-based Ariad (NASDAQ: ARIA). A previous trial showed that about 12 percent of patients on the Ariad drug developed a serious adverse event known as pancreatitis, when they got doses that ranged as high as 60 milligrams once a day. But Ariad chose to lower the dose for the pivotal study to 45 milligrams once daily, and it has reduced the rate of pancreatitis to 15 cases out of 403 patients (3.7 percent), according to data being posted today on the American Society of Hematology (ASH) website. The findings are based on about two months of follow-up data, and more updated information will be presented at the ASH conference next month in San Diego.
“The most common question I get about this drug is safety with pancreatitis, and this data should put that issue completely to rest,” Berger says. He added that no patients dropped out of the study because of pancreatitis, and that the condition these patients have developed is mild and treatable with fluids.
“It’s completely a non-event,” he says.
Analysts will be combing through this data carefully today, because much of Ariad’s value is based on this drug, which is being positioned for FDA approval just behind its lead drug candidate for bone cancer. The second Ariad product is seeking to treat patients with chronic myeloid leukemia and acute lymphoblastic leukemia that overexpresses what’s known as the Philadelphia chromosome.
Novartis has two drugs in this category, including imatinib (Gleevec), the dominant player in the market with $3 billion in worldwide sales, and Bristol-Myers Squibb has a rival product dasatinib (Sprycel). But Ariad is betting that there will be room in the market for its molecule, too. The Ariad drug is designed to block a broader number of variations on the key biological target, BCR-ABL, than the existing drugs do. The hope is that should enable Ariad to treat patients who eventually relapse on the other therapies, and the 10-15 percent of patients who don’t respond at all to existing drugs because they have a mutation known as T315i.
By going after patients who resist existing treatments, and those with the T315i mutation, Ariad’s drug could generate more than $500 million a year in sales, according to JP Morgan analyst Cory Kasimov, in a note to clients on Nov. 1.
The remaining data on safety were consistent with other drugs in this class, Berger says. Researchers are reporting that 15 percent of patients had moderate-to-severe depletion of clot-forming platelet cells (thrombocytopenia); while other common side effects were rash, muscle pain, abdominal pain, and dry skin. Out of the 403 enrolled patients, there were five serious cases each (1.2 percent incidence) of diarrhea, anemia, fever associated with white-blood cell depletion (febrile neutropenia), and fever.
Unlike most cancer drugs, which tend to have their greatest effect early in treatment and decline over time, the Ariad product appears to get more effective with time.
Patients on the Ariad drug were only followed up for a median time of 57 days, so the results on effectiveness are still quite preliminary. Ariad plans to continue following patients, and should have at least a median of six months follow-up data by the time it’s ready to file its new drug application to the FDA in mid-2012, Berger says. The patients in the study were quite sick, as 94 percent had their disease worsen after getting two or more drugs in the class, and 57 percent had worsened after getting three or more of the other drugs.
That said, the Ariad drug’s effectiveness rate looks consistent with the prior trial at the same point in time, with about two months of patient follow-up, Berger says. At this snapshot with a median of 57 days of follow-up, 38 out of 83 patents with the chronic phase of chronic myeloid leukemia (46 percent) had reached the primary goal, defined as a major cytogenetic response. For those of you who want to dig into the data cohort by cohort, you can check this copy of the study abstract and a slide from Ariad.
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