FDA Identifies ‘Systemic Bias’ in Amgen’s Late-Stage Lumakras Trial Ahead of Adcomm

FDA Identifies 'Systemic Bias' in Amgen's Late-Stage Lumakras Trial Ahead of Adcomm

As an FDA advisory committee prepares to deliberate on the data supporting Amgen’s groundbreaking drug Lumakras, a pre-meeting briefing document from the agency hints at potential challenges ahead for the KRAS inhibitor. Scheduled for discussion on Thursday, the FDA’s Oncologic Drugs Advisory Committee is poised to evaluate the feasibility of converting Lumakras’ accelerated approval into a full-fledged endorsement, with a specific focus on Amgen’s late-stage trial, named CodeBreaK 200.

In the lead-up to the meeting, the FDA has raised several concerns regarding the study, notably emphasizing what it deems “multiple sources of systemic bias” that cast doubts on the overall adequacy of the trial.

“Issues in study conduct, high rates of censoring, loss of follow up of patients who withdrew consent, and potential loss of randomization may not allow for adequate analysis of the trial’s results.” 

– FDA 

Currently, Lumakras holds approval for the treatment of KRAS G12C-mutated non-small cell lung cancer following a prior systemic therapy, albeit in an accelerated approval status. Amgen is now striving to secure full approval for the same indication.

Also Read: Amgen Unveils Exciting First-Line KRAS G12C NSCLC Data: Lumakras (Sotorasib) With Chemotherapy Shines At WCLC

Lumakras marked a pivotal milestone as the first FDA-sanctioned therapy targeting the once-considered “undruggable” KRAS mutation, previously dubbed the “Achilles’ heel” of lung cancer tumors.

The drug has contributed significantly to Amgen’s growth, although its early commercial performance has faced occasional setbacks. In the previous year, Lumakras achieved full-year sales of $285 million. Nonetheless, certain challenges have emerged. Beyond the concerns outlined in the FDA briefing document related to the CodeBreaK trial, the drug has previously raised safety red flags when used in potential combination regimens.

Also Read: Mirati’s KRAS Inhibitor Krazati Faces Rejection In Europe

During the previous summer, a study combining Lumakras with either Merck’s Keytruda or Roche’s Tecentriq disclosed a noteworthy incidence of severe liver toxicity at grades 3 or 4, affecting approximately 50% of patients. Although the study was relatively small, these results prompted questions about the feasibility of combination approaches involving the drug. 

In the meantime, Mirati Therapeutics’ rival Krazati has been closely trailing Lumakras. Krazati, which serves as Mirati’s inaugural commercial product, secured accelerated approval for the same indication late last year and is currently under investigation in combination with Keytruda. Encouragingly, this combination has not exhibited the same liver toxicity concerns.
Krazati has reported nearly $20 million in sales during the first half of 2023, underscoring its growing presence in the market.

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