Ariad Pharmaceuticals’ (NASDAQ: [[ticker:ARIA]]) plans to go head to head with imatinib (Gleevec) just went up in smoke.
In a big setback for the Cambridge, MA-based biotech, Ariad said Wednesday that it has halted its ongoing clinical trials of ponatinib (Iclusig), including a key study testing the drug as a frontline treatment for patients with chronic myeloid leukemia, due to safety concerns.
Ariad’s shares fell off a cliff during pre-market trading, sliding more than 60 percent before the opening bell.
The FDA approved ponatinib in December for patients with CML who are resistant to or can’t tolerate prior treatments—chiefly imatinib, Novartis’ blockbuster pill, and the other tyrosine kinase inhibitors on the market—and patients with Philadelphia-chromosome positive acute lymphoblastic leukemia.
Ariad’s drug is mostly used as a third-line treatment, however, so the company was shooting for a bigger share of the market. It had designed a series of pivotal trials pitting ponatinib against imatinib, hoping that it could prove it had the most effective therapy around for CML.
The effort, however, came up short. Although the FDA approved ponatinib last year, it did so with a black-box warning instructing doctors to watch out for blood clots and liver toxicities. Though Ariad officials said they didn’t expect the warnings to affect sales of the drug, they’ve proved to be a harbinger of things to come.
That’s because toxicities have piled up at a higher than expected rate as Ariad has tracked more patients taking its drug. Ariad reported today that serious blood clots occurred in 11.8 percent of the patients dosed with its drug after a 24-month follow-up, compared to 8 percent of the patients it had tested after 11 months. It said about 20 percent of patients that took ponatinib, combined had either “non-serious” or serious adverse events.
As a result, Ariad has stopped enrolling new patients in the studies—the FDA has placed a partial clinical hold on new patient enrollment in kind. In addition, Ariad will dial down the dose patients are already taking in the study from 45mg—the already approved dose—to 30mg, unless they’ve achieved a “major molecular response,” meaning they’re shown to have a very low amount of the BCR-ABL protein in the bone marrow (BCR-ABL is the molecular target of Ariad’s drug). Should that happen, their dose will be slashed to 15mg. Ariad will also no longer enroll patients who have had blood clots in the past that have resulted in heart attacks or strokes.
Ariad said that, as of now, the prescribing information for ponatinib hasn’t changed. But it is in talks with the FDA and other authorities about changes to the label.
Ponatinib is Ariad’s only approved drug, and its prospect as a front-line CML treatment is key to its success. RBC Capital Markets analyst Michael Yee noted, for instance, that such positioning is needed to support its current valuation.
Ariad held a conference call this morning at 8:30 a.m. ET to discuss the news with analysts.
