Maryland: The FDA has taken Bristol Myers Squibb to task for making false or misleading claims about the efficacy of Krazati on the website for the KRAS cancer drug.
Krazati, which BMS acquired in its $5.8 billion takeover of Mirati Therapeutics, has accelerated approval in KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer. BMS presented data from the trial that supported authorization on the efficacy page of a Krazati website aimed at healthcare professionals. The FDA and multiple complainants have taken issue with the efficacy page.
Leaders from the FDA’s Office of Prescription Drug Promotion set out the perceived problems with the page in an untitled letter to BMS. The letter describes issues with multiple measures of efficacy shared on the Krazati website.
The disease control rate (DCR) tab on the website states 80% of patients experienced tumor shrinkage of any magnitude and presents a waterfall plot. According to the FDA, the page “misleadingly suggests that Krazati improves DCR and ‘depth of response’ … even though the study was not designed to demonstrate this.”
As a single-arm trial that used objective response rate (ORR) and duration of response (DOR) as efficacy endpoints, the FDA said Mirati’s study didn’t demonstrate that cases of stable disease were attributable to Krazati. As such, the FDA found fault with the presentation of data on DCR, which combines the ORR and stable disease rate.
The agency also accused BMS of making misleading claims about overall and progression-free survival. In that case, the FDA’s criticism centers on the presentation of time-to-event efficacy endpoints from a single-arm trial.
“Time-to-event efficacy endpoints in single-arm trials are generally uninterpretable because it is not possible to determine if the observed effect (e.g., survival time) is attributable to the drug or the natural history of the disease. Evaluation of time-to-event endpoints requires randomized controlled trials,” the FDA said. BMS’ notice that the survival analyses are “descriptive” failed to save it from the FDA’s ire.
There’s more. The Krazati website lists the DOR as 12.5 months, again under the banner “descriptive analysis.” As the FDA points out, the label for Krazati puts the DOR at 8.5 months. BMS cited “data on file” including “pooled DOR” information to support the claim of 12.5 months. The FDA ruled the figure overstates the efficacy of Krazati, noting that “pooling data poses analytical problems.”
The agency finished off its dissection of the website with a breakdown of its issues with a tab about the intracranial ORR and DCR seen in the study. Again, BMS based the claims on a single-arm study. Most of the patients in the analysis were previously treated with radiation therapy for brain metastases, the FDA said, and the results may reflect the effects of that treatment, not Krazati.
The untitled letter is dated Aug. 1 and gives BMS 15 working days from receipt to address the concerns in writing. The website still featured the data challenged by the FDA as of the morning of Aug. 8.
