After a PhIII failure, the FDA delivers Blueprint an expected CRL
Some CRLs come as little surprise.
This morning, the FDA rejected Blueprint Medicines’ application to have their cancer drug Ayvakit (avapritinib) approved for fourth-line gastrointestinal stromal tumors, or GIST. Already, though, in late April, the drug had failed the major test for that indication: A Phase III trial pitting Ayvakit against the already-approved Bayer GIST drug, regorafenib.
Patients on regorafenib did better than those on Ayvakit. After the trial, Blueprint said they were ending the program for 3rd and 4th line GIST patients. Analysts discounted the indication from their projections.
“Blueprint will provide the VOYAGER data to the FDA as part of the ongoing review of avapritinib in 4L GIST (PDUFA May 14), though expects that an approval is unlikely,” Cowen’s Marc Frahm wrote in a note to investors.
Today’s announcement was set up by a split decision the FDA made in January. Although Blueprint was facing a February PDUFA, the agency chose to address the two indications addressed in Blueprint’s NDA separately, handling one early and booting the other down the road.
For GIST patients with a rare mutation with PDGFRa, the FDA saw clear benefit for the drug, with Ayvakit showing an 84% response rate. But in general fourth-line GIST, the agency wanted more data. They delayed the deadline to May 14, by which time the Phase III trial would have results.
With the Phase III failure already out, the official CRL changes the forecast little for Blueprint, but even when the study results emerged, analysts urged against panic. “GIST was not the thesis,” Frahm wrote, noting that Blueprint was moving ahead in RET-positive cancers and a rare disease called systemic mastocytosis, where investors saw greater potential.
In the ASCO abstract dump earlier this week, Blueprint revealed data from their RET-targeted cancer drug pralsetinib, showing a few complete responses and almost matching Eli Lilly’s recently approved Retevmo on overall response — setting up a potential dual market for years.
The best promise for GIST patients without the PDFRa mutation now lies with Deciphera, which has been going to head to head with Blueprint on the indication for a year. The company’s drug, ripretinib, has earned a breakthrough designation and a priority review for fourth-line GIST, setting up a decision in August. The drug is designed to target not only PDGFRa but the KIT mutations that fuel a majority of GIST tumors.
In a late-stage study of 129 patients, the drug produced a progression-free survival of 6.6 months compared to 1 month in placebo, although the response rate was only 9.4%. A study comparing its effects in second-line patients to the effects of Pfizer’s Sutent is ongoing.