Mirati trips over the finish line
Accelerated approval for Mirati’s Kras inhibitor adagrasib – now trademarked Krazati – failed to lift the biotech’s beaten down stock this morning. The drug’s second-line NSCLC label compares favourably with Amgen’s rival agent Lumakras on efficacy, with no black box warning of QTc prolongation as feared, although potentially differentiating CNS data were omitted. On a call executives revealed that the confirmatory pivotal trial Krystal-12, which pits Krazati versus docetaxel, was moving to a dual primary endpoint of PFS and OS with enrolment almost doubling to 600 subjects. Mirati said this was agreed “in conjunction” with the FDA; the regulator presumably has Amgen’s struggles to show a survival benefit in its confirmatory phase 3 trial in mind. This shift gives Mirati the chance to outshine, but the trial will take longer to report and becomes more risky. Doubts about the first-line lung cancer opportunity are also growing, after data disappointed earlier this month and Mirati laid out a phase 3 strategy that involves trying to beat Keytruda, with or without chemo, in the various PD-1 expression cohorts. Investors' reaction to all this speaks volumes: the group's stock has more than halved since that disclosure, and dropped a further 10% at today's open, hitting a four-year low.
|Squaring off in second-line Kras mutated NSCLC|
|ORR||mDOR||Patients with duration ≥ 6 months||Hepatotoxicity (drug-induced liver injury)|
|Krazati||43% (n=112)||8.5 months||58%||1.7% (all grades) and 1.4% (Grade 3)|
|Lumakras||36% (n=124)||10.0 months||58%||0.3% (all grades) and 0.3% (Grade 3)|
|Source: FDA drug labels.|