Deciphera's GIST therapy ripretinib wins speedy FDA review — setting the stage for battle with rival Blueprint
Blueprint Medicines has the edge on timing with its rival cancer drug Ayvakit, but Deciphera Pharmaceuticals is not far behind. On Wednesday, the Waltham, Massachusetts-based company disclosed it had secured a speedy review for its drug ripretinib and an August decision date.
Both precision therapies are designed to treat gastrointestinal stromal tumors (GIST) — a rare form of sarcoma found in the digestive system, most often in the wall of the stomach.
Last month, Blueprint scored accelerated approval for Ayvakit in patients with unresectable or metastatic GIST harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations on the basis of data that showed an overall response rate of 84%.
But the company’s application to market the drug in fourth-line GST patients — the indication Deciphera’s ripretinib is gunning for — was pushed to May 14. The FDA is expected to make its decision on the Deciphera therapy by August 13.
Ripretinib has a breakthrough drug designation, which should speed things along at the FDA that of late has no problem moving ahead of schedule, especially when it comes to oncology therapies for patients with few options.
“Ripretinib was accepted for priority review under the FDA’s RTOR program, which is an effort to expedite the approval process for drugs that are deemed important as new therapies by a more interactive process between the Agency and the Sponsor,” SVB Leerink’s Andrew Berens wrote in a note. “As such, we would anticipate that the drug will be approved ahead of the August 13th action date (PDUFA), as have other drugs entered in this RTOR program and/or been granted BTD.”
Deciphera wasted no time in announcing a new round of funding — just over 10 minutes after the PDUFA date was unveiled publicly — offering $250 million in shares of its common stock, roughly six months after it raised $400 million on the back of largely positive late-stage data.
The raise may signal that a buyout — which was the result in the case of targeted therapy developers Loxo and Array — is unlikely.
“In our view, many investors had anticipated an acquisition ahead of the GIST launch, which appears unlikely following this raise,” Berens said. “The company indicates that the proceeds will help fund pipeline advancements, trial expansion, and preparations for a commercial launch of ripretinib.”
In a majority of patients with GISTs, the cancer cells have a tweaked KIT oncogene. This gene directs cells to make the KIT protein, which causes the cells to uncontrollably grow and divide. In some 5% to 10% of GISTs, the cancer cells have a mutation in the PDGFRA gene, which causes the cells to make too much of the PDGFRA protein, according to the American Cancer Society.
While approved kinase inhibitors control certain initiating and drug resistance-causing mutations in KIT and PDGFRα, no existing therapy can inhibit all known mutations. Deciphera’s ripretinib is designed to thwart the full spectrum of known mutations in KIT and PDGFRα.
Data from a 129 patient late-stage study testing ripretinib in GIST patients who had been previously treated with at least three therapies showed it improved progression-free survival by 6.3 months versus 1 month in the placebo group. But the overall response rate (ORR) was 9.4% (compared to 0% in the control group) — not a statistically significant result. And although the trial was not powered to undertake a formal analysis of overall survival without a successful hit on ORR, researchers had a look anyway — finding a positive 15.1 months for the drug versus 6.6 months for the control arm. To recoup the ORR miss, the company added some updated early-stage data from a separate follow-up study of second- to fourth-line patients.
Ripretinib is also being tested as second-line therapy in GIST patients against Pfizer’s Sutent in the late-stage INTRIGUE trial. In a separate filing on Wednesday, the company said it was expanding the sample size of the study.
“The expanded sample size, the magnitude of which has not been disclosed, is expected to be implemented to allow the company to maintain the power of the trial by accomplishing the pre-specified number of events. While this explanation appears reasonable, we anticipate that it could cause some concern among investors…” Berens said. “We also believe some investors may question the timing of the disclosure relative to the offering.”