Blueprint Medicines has its first product approval, claiming an FDA green light for Ayvakit as a treatment for gastrointestinal stromal tumours (GIST) caused by a rare mutation.
The US regulator has cleared Ayvakit (avapritinib) – a KIT and PDGFRA inhibitor – for adults with GIST that can’t be treated with surgery or has spread around the body and expresses a mutation on exon 18 known as PDGFRA D842V.
“GIST harbouring a PDGFRA exon 18 mutation do not respond to standard therapies for GIST,” according to the FDA’s head of oncologic diseases Richard Pazdur.
“Today’s approval provides patients with the first drug specifically approved for GIST harbouring this mutation,” he said, a group which accounts for around 6% of all newly-diagnosed GIST cases. Around 5,000 people in the US are diagnosed with GIST per year.
Blueprint claimed the approval on the strength of a phase 1 trial – called NAVIGATOR – which showed that Ayvakit achieved tumour shrinkage in 84% of 43 patients with this mutation.
And while targeted therapies can often have limited duration of action due to the emergence of resistance, the median duration of response still hasn’t been reached in the study, with 61% of the responding patients with exon 18 mutations achieved a response lasting six months or mor
The tiny trial indicates just how rare this type of cancer is, and Blueprint has priced its product accordingly, at $32,000 for a 30-day supply, regardless of the dose needed by the patient.
It has indicated it will launch Ayvakit onto the market within a week, but analysts at Cowen & Co aren’t expecting big sales given the tiny patient population, predicting peak revenues of $68m in 2032.
The approval “ushers in a new era of precision medicine in this disease,” according to NAVIGATOR investigator Michael Heinrich of Oregon Health & Science University in the US.
It represents “a call to action to conduct mutational testing in all patients with GIST before initiating kinase inhibitor therapy, as recommended by clinical guidelines, so appropriate patients may realise the benefits of this promising new medicine”.
Chemotherapy and radiotherapy is notoriously ineffective in GIST. At the moment the standard approach to treating patients who aren’t eligible for surgery is older kinase inhibitor drugs like Novartis’ Glivec (imatinib) and Pfizer’s Sutent (sunitinib), which are also available as generics, and Bayer’s Stivarga (regorafenib) which is still in patent.
Blueprint has also filed for approval of Ayvakit as a fourth-line therapy for ‘all-comer’ GIST patients who have progressed on earlier therapies, and says it is expecting a verdict from the FDA next month for this indication, which could expand the usage of the drug significantly.
The FDA’s decision has been delayed by three months as Blueprint awaits data from a head-to-head trial of Ayvakit versus Stivarga in third- or fourth-line GIST treatment.
Competition could come not too far down the line from Deciphera’s KIT and PDGFR inhibitor ripretinib, which in October generated positive results in a phase 3 trial in heavily pre-treated GIST patients, extending progression-free survival to six months from one month with placebo.