Rationale Behind the Recent FDA PD-1 Inhibitor Label Restrictions

PE: Can you explain the FDA’s reasoning behind targeting the broad labeling of PD-1 inhibitors and how this might impact future drug approvals in oncology?

Lanton: I think the change in labeling is going to push both providers and patients to file challenges, because, again, that access to treatment, I think it's already opened the door to product liability issues. I have a quote from the FDA that says ‘If patients with low or no PD-1 expressions are not expected to benefit based on the available data, then administering anti-PD1 therapy has the potential for harm, including serious immune related adverse events on top of a maladency that could markedly affect a patient's quality of life.’ After looking at that, I think either way, manufacturers and insurance companies are going to be sued on access either to the treatment because the narrow language to label or because of possible adverse effects allowed under a broader label.

Full Interview Summary: The FDA’s recent challenges to the broad labeling of PD-1 inhibitors for gastric cancers, particularly around PD-L1 expression, could have far-reaching legal, regulatory, and strategic implications for pharmaceutical companies and healthcare providers. This shift could significantly restrict patient access to these treatments by mandating a threshold for PD-L1 expression, which is anticipated to exclude a large portion of patients, particularly those with low PD-L1 expression levels. These patients, lacking alternative treatment options, may initiate litigation, claiming denial of necessary treatment.

From a regulatory standpoint, companies will need to revise labeling to specify PD-L1 thresholds, impacting compliance procedures and possibly requiring additional studies. This narrowing of indications is also likely to increase the cost of these therapies, potentially limiting their inclusion in insurance formularies and intensifying market access challenges. Consequently, insurers might also face legal scrutiny from patients and providers who feel that access is unfairly limited due to the new labeling standards. Moreover, product liability claims could arise if adverse events occur under a broader indication, adding further risk.

Pharmaceutical companies may argue that biomarkers can restrict access, which could touch on genetic discrimination concerns, though the Genetic Information Nondiscrimination Act (GINA) may limit this defense’s applicability. This labeling challenge could also impact future drug development strategies, as companies may become more cautious about targeting treatments based on specific biomarkers. The FDA’s stance may deter innovation by slowing research and development (R&D) timelines, as companies may hesitate to invest in drugs with narrow patient populations. This situation may also rekindle debate around Right to Try laws, which aim to broaden treatment access for critically ill patients. Overall, the FDA’s challenge is poised to reshape market dynamics and legal risks, creating a complex landscape for manufacturers and healthcare providers alike.