Cambridge biotech Ariad Pharmaceuticals Inc. abruptly terminated a pivotal clinical trial of its leukemia drug Friday, a move that raised new safety questions and sent the company’s shares plunging more than 40 percent.
By ending the late-stage trial of Iclusig, Ariadessentially abandoned a plan that had been considered key to its future: turning the pill — already on sale in the United States and Europe for use by patients whose cancers resist other treatments — into a “first-line” medicine for those newly diagnosed with chronic myeloid leukemia.
Ariad executives said they decided, in concert with the Food and Drug Administration, to discontinue their so-called Epic clinical study after early data from 150 sites in 20 countries showed patients taking Iclusig in the study experienced problems such as blood clots leading to heart attacks, strokes, and blocked arteries. The company didn’t immediately disclose how many patients suffered those side effects or whether any died.
“The prudent course of action was to stop testing the drug in early-stage patients and focus our efforts on patients with resistant forms’’ of chronic myeloid leukemia and other tumors, Ariad chief scientific officer Timothy P. Clackson said in an interview Friday. “The best decision for patient safety and for the development of the drug was to terminate the trial.”
Ariad’s move came nine days after the FDA placed a “partial clinical hold” on all of the company’s Iclusig trials, including trials for patients with thyroid and gastrointestinal cancers. The biotech stopped enrolling new patients until it develops new trial rules, and the FDA updates a warning label for the blood-cancer therapy.
Since then, Ariad’s stock has dropped by 84.4 percent on the Nasdaq exchange as analysts reassessed its value in light of the safety concerns.
“The assumption is there will be a narrower label” for Iclusig, said Howard Liang, managing director at health care investment bank Leerink Swann in Boston. “The expectation is that this will be used as a salvage drug for patients who have no other options.”
That means the market for the treatment will be much smaller than what the company was counting on.
Investors, already wary about Ariad’s future, reacted quickly to the latest setback Friday. The company’s stock fell $1.83 to $2.67 a share, a one-day drop of 40.6 percent.
FDA officials have not said when they will issue a new Iclusig label that would incorporate safety data from the Epic trial and possibly adjust dosing for the treatment. In the trial, Iclusig went head-to-head with Gleevec, a Novartis leukemia drug that is the market leader with about $3 billion in annual sales.
Separately, regulators from the FDA are discussing with Ariad executives whether to modify dosing and patient eligibility for about a dozen other Iclusig clinical trials that are continuing, even though Ariad has temporarily stopped enrolling new patients.
“The FDA’s investigation is ongoing, and we are actively working with Ariad to further evaluate these adverse events,” agency spokeswoman Stephanie Yao said in a statement. “We will notify the public when more information is available.”
Iclusig was approved by the FDA last December to treat two rare cancers — chronic myeloid leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia — for patients who can’t tolerate existing therapies, or have developed resistance to those medicines.
Yao said US doctors “should consider for each patient whether the benefits of Iclusig treatment are likely to exceed the risks of treatment.” She urged patients taking the drug to seek immediate medical attention if they experience heart attack symptoms such as chest pain or pressure; pain in their arms, back, neck, or jaw; or shortness of breath; or stroke symptoms such as numbness or weakness on one side of the body, trouble talking, headache, or dizziness.
The recommended starting dose for Iclusig sold commercially is the same as the dose used in the Epic clinical trial. But doctors, trial sponsors, and regulators often allow patients whose cancer is more advanced — those who have previously taken other drugs that are no longer working — to accept more safety risks than newly diagnosed patients such as those in the Epic trial.
“While the hope is that clinical trials will show that therapies are safe and effective, it is just as important to know when there are safety issues,” said Andrea Greif, spokeswoman for the Leukemia & Lymphoma Society in White Plains, N.Y. “This is the clinical trial process at work.”
Greif said her patient advocacy group, which helps fund blood-cancer research, looks forward to understanding the new safety data when it becomes available, and to advising patients on the implications. Society officials previously have said patients had high expectations for Iclusig, which was considered a potent medicine designed to bind to tumors and block the mutations that have undermined existing therapies.
In an quarterly earnings report next month, Ariad executives are expected to address the changed market outlook for Iclusig and discuss a new financial plan for the company, which is scheduled to move into a new Kendall Square headquarters in 2015.
“It would be naive to think there will be no effect” on the leukemia drug’s sales in the United States and Europe, said Ariad’s Clackson.
“Obviously this has been a challenging time for us,” he said. “But we absolutely remain committed to the safe and effective development of Iclusig.”