Trial flop busts Deciphera's blockbuster hopes for Qinlock
Shares in Deciphera Pharma went into freefall on Friday after top-line results of a phase 3 trial of its Qinlock in rare cancer gastrointestinal stromal tumour (GIST) dashed its hopes of moving the drug earlier in treatment.
KIT inhibitor Qinlock (ripretinib) was approved by the FDA last year as a fourth-line therapy for GIST in adults who have received prior treatment with three or more kinase inhibitor therapies, including tyrosine kinase inhibitor (TKI) imatinib, sold by Novartis as Gleevec and also available generically.
That approval came after the FDA rejected rival therapy Ayvakit (avapritinib) from Blueprint Medicines, effectively ceding much of the target market to Deciphera.
That prompted analysts to predict sales of upwards of $1.5 billion a year – assuming it could move further up the treatment pathway.
Fast forward to now, and those predictions are looking all-but impossible to reach. In the latest phase 3 study, Qinlock was unable to improve on Pfizer's Sutent (sunitinib) when it came to preventing disease progression or death when used as a second-line therapy for GIST after first-line imatinib.
Progression-free survival was 8.3 months with Sutent and eight months with Qinlock, and while there was a modest trend in favour of Deciphera's drug for a subgroup of patients with exon 11 KIT mutations, it wasn't statistically significant.
Deciphera's sales of Qinlock in its current fourth-line use are modest at around the $20 million mark for each of the last three third quarters, which analysts have suggested could be around its top US sales expectation with the current label.
There is a little upside from an expected approval in Europe for fourth-line GIST in the coming weeks, but that is small comfort in comparison to the failure of the second-line INTRIGUE study. Shares in Deciphera were down 75% on Friday after the news was announced.
Steve Hoerter told investors on a conference call that the company was "surprised and disappointed" by the results, adding it believed the trial was "robust, well-designed, and well-executed."
He also said Deciphera was starting a review of its portfolio in the wake of the disappointment, which will include possible future directions the company could go with Qinlock in GIST. The company has an inhibitor of CSF1R – vimseltinib – which is due to start a phase 1/2 trial in tenoysynovial giant cell tumour (TGCT) before the end of the year.
Other early-stage programmes include rebastinib, a TIE2 inhibitor for solid tumours in combination with paclitaxel, and ULK inhibitor DCC-3116 which is being developed initially for RAS/RAF mutant cancers in combination with trametinib.
Hoerter noted that there are roughly the same number of patients with GIST in the major European markets as the US, although post-approval pricing negotiations makes it hard to gauge the potential revenues from Qinlock from the region.
