The Food and Drug Administration on Monday approved Mirati Therapeutics’ targeted lung cancer drug Krazati, a victory for the San Diego biotechnology company in its bid to challenge a rival treatment from Amgen.
The approval is also another advance for drugmakers’ efforts to target a gene called KRAS that, when mutated, is implicated in the growth of many lung, pancreatic and colon cancers. For years considered “undruggable,” KRAS only recently came within reach of drug researchers, sparking a flurry of clinical trial activity and, last year, the first approval of a KRAS-blocking medicine in Amgen’s Lumakras.
Mirati has been following close behind Amgen with its development of Krazati, which targets the same kind of mutation in the KRAS gene as Lumakras. While the drug’s approval is a win, Mirati will now have to compete with a much larger rival, as well as contend with diminishing sales expectations for this first generation of KRAS-blocking drugs.
The FDA’s clearance for Krazati is similar to the one it gave Lumakras. Both drugs are approved to treat adults with locally advanced or metastatic non-small cell lung cancer who have previously received at least one systemic treatment. Their use is limited to treating only those tumors that test positive for what are known as G12C mutations in the KRAS gene.
They carry slightly different safety warnings, however. Krazati’s labeling notes gastrointestinal side effects and a type of heart rhythm disruption known as QTc prolongation, while Amgen’s cautions of interstitial lung disease. Both come with liver toxicity risk, which has cropped up as a particular concern in testing of Lumakras with a kind of cancer immunotherapy.
Mirati will charge slightly more for Krazati than Amgen does for Lumakras, setting a list price of $19,750 for about a month’s supply of the drug. Lumakras costs $17,900 per month at list price.
“KRAS has been a difficult to treat mutation for years,” said Charles Baum, Mirati’s founder and head of R&D, in an email. “With the approval of Krazati, oncologists have a new treatment option for patients with KRASG12C-mutated advanced NSCLC that they can add to their arsenal and ultimately provide more options for their patient’s treatment journey.”
In a single-arm Phase 2 trial of 112 patients, 43% responded to treatment with Krazati, slightly higher than the response rate reported in the comparable study of Lumakras. Responses lasted a median of 8.5 months, data showed. Pooled data from the trial and an earlier study showed Krazati-treated patients lived a median of 14 months.
While modest, the efficacy of the two drugs is still an improvement over what would be expected with chemotherapy in patients whose lung cancer has already progressed after immunotherapy and chemo. Still, many cancer doctors see a larger role for KRAS inhibitors to be used in combination with other medicines, like Merck & Co.'s Keytruda, than on their own as monotherapies. This thinking, along with a growing understanding of the drugs' safety risks, has led analysts to tamp down their forecasts of how high sales will climb.
On that front, Mirati has been running a mid-stage study called KRYSTAL-7 testing Krazati together with Keytruda. Early results presented Dec. 5 appeared to show stronger response rates and less liver toxicity than Lumakras did alongside immunotherapy in a separate study, although comparing across studies can be misleading due to differences between them.
Mirati is expanding KRYSTAL-7 into a Phase 3 trial and plans to run a second pivotal study of Krazati plus Keytruda in previously untreated lung cancer patients with a certain genetic signature in their tumors.
Follow-up testing will also be important for Mirati to convert Monday’s approval, which was granted on a conditional basis by the FDA, to a full clearance. Another study, called KRYSTAL-12, is comparing Krazati to the chemo drug docetaxel in previously treated non-small cell lung cancer.
Amgen’s a step ahead there, having already read out results from a Phase 3 study that showed Lumakras outperformed docetaxel, although the data did not yet prove the drug can help patients live longer.
KRAS G12C mutations are present in an estimated 13% of patients with non-small cell lung cancer. About 25,000 people are diagnosed each year with lung tumors that harbor the mutation. The number who have failed first-line treatment and would be eligible for Krazati is much smaller, however, at about 7,000, according to Mirati.
Shares in Mirati were down about 3% in Tuesday morning trading, and have fallen by about three-quarters this year as analysts have adjusted their sales expectations for KRAS inhibitors. Lumakras generated $75 million in sales last quarter, well below consensus estimates of $89 million.