The United States Food and Drug Administration (FDA) Office of Prescription Drug Promotion (OPDP) recently sent an untitled letter to Mirati Therapeutics for claims made by the company about the efficacy of its cancer drug approved to treat patients with certain kinds of lung cancer, Krazati (adagrasib) on its website. Krazati was approved by the FDA under the accelerated approval pathway, based on results from the KRYSTAL-1 multicenter, single-arm, open-label expansion cohort study that evaluated objective response rate (ORR) and duration of response (DOR) as its clinical endpoints.
The determination of whether a promotional communication is misleading includes not only representations made or suggested in the promotional communication, but also the extent to which the promotional communication fails to reveal facts material in light of the representations made.
According to OPDP, the company makes claims about outcomes from a clinical trial that was not intended to measure such claimed outcomes. “The website makes false or misleading claims and representations about the benefits of Krazati,” said OPDP in the untitled letter. “These violations are particularly concerning because the promotional communication makes misleading representations about the efficacy of Krazati in patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC).”
The letter goes on to cite statistics from the American Cancer Society, Metastatic NSCLC is an incurable condition with a 5-year survival rate of less than 10%, and lung cancer is a serious public health concern and treatment for this condition involves serious risks. Lung cancer is by far the leading cause of cancer death in the United States, accounting for about 1 in 5 of all cancer deaths.”
According to the letter, OPDP took issue with claims made by Mirati that the disease control rate (DCR) in patients taking the drug is 80% and that tumors shrank (“of any magnitude”) in 80% of Krazati patients in the KRYSTAL-1 clinical trial. OPDP believes those statistics are misleading because it uses composite data of stable disease, partial response, or complete response in patients who took the drug, even though the trial was not designed to evaluate the depth of response.
The website also claimed that the median overall survival in patients taking Krazati was 14.1 months and the median progression-free survival in Krazati patients was 6.9 months, presented along with two graphs depicting “Survival Probability” and PFS Probability” over time.
“It is misleading to include in promotional materials representations or suggestions that rely on a study or studies whose design is not capable of supporting such representations or suggestions,” said OPDP. “Since KRYSTAL-1 was a single-arm trial, it is not known whether the data on [stable disease] are attributable to treatment with Krazati.” Therefore, the agency notes, “the DCR calculations, which are based on a composite that includes [stable disease] data, and the associated ‘depth of response’ claim, are not supported by the data cited.”
Mirati was allowed 15 working days to dispute the FDA’s allegations of violations or explain the steps it is taking to remedy the situation.