Blueprint stumbles in PhIII GIST trial, sending stock sliding, but analysts preach caution
When the FDA approved Blueprint’s first drug three months ago, they split their decision. Ayvakit would be approved for gastrointestinal stromal tumors (GIST) with a rare mutation called PDGFRa. The other half of their application for plain old fourth line GIST would have to wait. Regulators wanted to know how the drug performed in a Phase III trial.
Results are now in from that Phase III trial and they spelled a death-knell. In a study of 476 patients with third or fourth line GIST, Ayvakit (avapritinib) performed worse on the primary endpoint than the already-approved Bayer GIST drug, regorafenib. Progression-free survival was 4.2 months, compared with 5.6 months for Ayvakit.
Blueprint’s drug did have a higher response rate — 17% compared with 7% — but that appeared as little consolation. The company is discontinuing development of the drug for those patients.
“We will continue to advance our pipeline with clear near-term priorities in systemic mastocytosis and RET-altered cancers,” CEO Jeff Albers said in a statement.
The company’s stock $BPMC took a significant hit, falling 20% from $70.90 to $56.71, effectively erasing over $800 million in value.
Cowen’s Marc Frahm suggested, though, that this was an overreaction, writing in a note to investors that “GIST was not the thesis.” The drug could still be potentially used off-label in fourth line GIST, Frahm wrote, but they were still removing 3rd and 4th line GIST from their future sales projections. Nevertheless, he argued the trial said little about Ayvakit’s potential in systemic mastocytosis — a rare disease where mast cells accumulate in organs — or, in combination with another experimental drug, in cancers with RET mutations.
“We have removed sales for the broad 3/4L GIST indications but continue to view BPMC shares as undervalued,” Frahm wrote, pricing them at $83.
Andrew Berens at SVB Leerink was less upbeat but echoed the call for caution. The failure will “fundamentally hit” Blueprint, he said, but the greater potential lay elsewhere.
“Overall, we believe that GIST is less important to the BPMC thesis and think that investors are likely to step in after this readout for more long-term opportunities in RET-driven malignancies and systemic mastocytosis (SM) with upcoming catalyst,” Berens wrote.
Blueprint had been in a two-person race with Deciphera to get a drug approved for GIST — a rare form of sarcoma in the digestive system — driven by a mutation to the platelet-derived growth alpha gene, or PDGFRa. Ayvakit was approved under accelerated approval, while Deciphera awaits an August decision date from the FDA. Both companies are also pursuing systemic mastocytosis and 2nd line GIST.
Deciphera does not have a trial for 3rd line GIST, but Berens said the company could benefit if oncologists decide to try their drug off-label in that setting.
Social image: Jeff Albers, Blueprint CEO (CNBC)