Only hours after Blueprint Medicines Corp. disclosed an FDA complete response letter for avapritinib in fourth-line gastrointestinal stromal tumor (GIST), Deciphera Pharmaceuticals Inc.’s kinase inhibitor, ripretinib, won the agency’s approval for the same indication, well ahead of its Aug. 13 PDUFA date. It's the company's first FDA-approved product, arriving about four-and-a-half years after Deciphera first submitted an IND for the medicine.
Branded Qinlock, the drug is approved for adults who have received prior treatment with three or more kinase inhibitor therapies, including imatinib (Gleevec, Novartis AG). During a pivotal phase III study, patients in the Qinlock group lived 5.3 months longer before disease progression or death vs. those in the placebo group. In addition, Qinlock demonstrated a median overall survival of 15.1 months compared to 6.6 months in the placebo arm and reduced the risk of death by 64% (hazard ratio of 0.36), Deciphera said.
Waltham, Mass.-based Deciphera plans to make Qinlock commercially available in the U.S. next week, at a list price for a 30-day supply of $32,000, or roughly $192,000 over six months. A phase III study that could support moving the drug into second-line GIST is underway, with expectations that its enrollment will be completed in the second half of this year.
"Despite the progress that has been made over the past 20 years in developing treatments for GIST, including four FDA-approved targeted therapies – imatinib in 2002, sunitinib in 2006, regorafenib in 2013 and avapritinib earlier this year – some patients don't respond to treatment and their tumors continue to progress," said Richard Pazdur, director of the FDA's Oncology Center of Excellence and acting director of its office of oncologic disease. "Today's approval provides a new treatment option for patients who have exhausted all FDA-approved therapies for GIST," he said.
Blueprint said Friday that it plans to continue to commercialize avapritinib, FDA-approved as Ayvakit, for the treatment of adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation and also to continue its development of that drug for the treatment of systemic mastocytosis. But based on top-line results of its phase III Voyager trial testing the drug in adults with unresectable or metastatic fourth-line GIST, reported in May, it had already said it would discontinue further development of the drug in broader GIST indications.
A rare tumor type
GISTs arise when abnormal cells form in the tissues of the gastrointestinal tract, something that happens most commonly in the stomach, small intestine and large intestine but can start anywhere along the gastrointestinal tract. About 4,000 to 6,000 adults are diagnosed with a GIST annually. Deciphera estimates there are about 1,000 to 1,200 patients in the fourth-line population.
The FDA's approval of Qinlock was based on the results of the international, multicenter, randomized, double-blind, placebo-controlled trial, Invictus. It enrolled 129 patients with advanced GIST. Each had received prior treatment with imatinib, sunitinib (Sutent, Pfizer Inc.) and regorafenib. The trial compared those randomized to receive Qinlock to those randomized to receive placebo, to determine whether progression-free survival (PFS) – the time from initial treatment in the clinical trial to growth of the cancer or death – was longer in the Qinlock group compared to the placebo group.
During treatment in the trial, patients received Qinlock or placebo once a day in 28-day cycles, repeated until tumor growth was found or the patient experienced intolerable side effects. On average, the PFS rate in patients in the Qinlock group was 6.3 months, compared to one month for patients in the placebo group. After disease progression, patients who were randomized to placebo were given the option of switching to Qinlock.
The most common side effects from the drug were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia syndrome and vomiting.
The FDA had granted Deciphera's application priority review and fast track designation, as well as breakthrough therapy and orphan drug status. The review used the agency's real-time oncology review, which streamlined data submission prior to the filing of the entire clinical application, and provided additional information to the agency to facilitate its assessment. Furthermore, the FDA collaborated with the Australian Therapeutic Goods Administration and Health Canada on the review of the application as part of Project Orbis.
Deciphera shares (NASDAQ:DCPH) rose 6.6% on May 15 to $51.69. Blueprint shares (NASDAQ:BPMC) shares fell 1.1% to $63.58.