Blueprint's Ayvakit gets FDA no-go in new stomach cancer use but presses ahead in blood disorder

The FDA rejected Blueprint Medicines' Ayvakit in heavily pretreated gastrointestinal stromal tumors, and the company has decided not to pursue any other GIST indications beyond its current label. (Blueprint Medicines)

The FDA previously split the review of Blueprint Medicines’ kinase inhibitor Ayvakit into two parts. Now months after granting the drug its initial stomach cancer go-ahead, the agency has denied it the second.

The FDA issued a complete response letter for Ayvakit’s application to treat gastrointestinal stromal tumors (GIST) in heavily pretreated patients, Blueprint said Friday. The drug in January became the first drug specifically approved for a small subset of GIST patients: Those who carry a PDGFRα exon 18 mutation.

The rejection isn’t a surprise, given that Ayvakit failed a phase 3 clinical trial in the broader group.

In April, Blueprint unveiled data showing Ayvakit failed to top Bayer’s Stivarga at staving off tumor progression or death in patients with third- or fourth-line GIST in the Voyager trial. While Ayvakit delivered a median progression-free survival of 4.2 months, Stivarga performed better at 5.6 months.

At the time, Blueprint management immediately decided not to pursue any further development of Ayvakit in GIST beyond its currently approved label.

Ayvakit’s failure could mean a win for competitor Deciphera, whose ripretinib is under FDA real-time oncology review in fourth-line GIST. But Blueprint isn't stopping its quest to expand Ayvakit's reach, just focusing it on a different disease.

RELATED: Blueprint hits goal in midphase rare disease trial, teeing up pivotal study

In March, part 1 of a phase 2 trial of Ayvakit in indolent systemic mastocytosis (iSM) returned positive results. The rare blood disorder is characterized by uncontrolled mast cell growth and can cause debilitating symptoms such as allergic reactions, fatigue and bone pain. Patient-reported outcomes showed the drug was associated with meaningful reductions in clinical symptoms, compared with placebo. After the readout, SVB Leerink analyst Andrew Berens labeled iSM a “tangible value driver” for Blueprint.

During the first quarter, Ayvakit’s sales reached $3.5 million, ahead of Berens’ previous estimate of $2 million.

Blueprint's chief commercial officer, Christy Rossi, said on a conference call last week, that the drug has attracted more than 100 prescribers and has secured coverage for more than 90% of commercial and Medicare lives.

“One of the things that I was very pleased to see starting really out of the gate is that we saw prescribing breadth that went beyond centers that were either participants in our clinical studies or where somebody had prior experience through compassionate use,” she said.

RELATED: Blueprint wins first FDA nod for a stomach cancer—though not exactly what it asked for

Besides Ayvakit, Blueprint is awaiting an FDA decision for its RET inhibitor pralsetinib—a potential rival to Eli Lilly’s newly approved Retevmo—in RET-driven non-small cell lung cancer.

In a phase 2 trial, pralsetinib triggered a response in 65% of patients with RET fusion-positive NSCLC, according to updated data set for presentation later this month at the American Society for Clinical Oncology virtual event.

Rossi touted Blueprint’s experienced staff ahead of its potential Ayvakit expansion into iSM and pralsetinib launch in lung cancer. “More than two-thirds of our team has worked in lung cancer, and more than 80% have worked in hematology, with a mix of large pharma and biotech launch experience,” she said during the call.