- Merck's blockbuster immunotherapy missed the primary endpoint of a late-stage study that tested it in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) — a disease the drug is already approved to treat.
- Keytruda (pembrolizumab) monotherapy failed to significantly improve overall survival (OS) compared to standard of care in the KEYNOTE-040 trial, which enrolled nearly 500 participants with HNSCC who hadn't adequately responded to one or more platinum-containing systemic treatments.
- Despite the setback, Merck said the label for Keytruda "remains unchanged," according to a Monday statement. The anti-PD-1 therapy was first green lit for the HNSCC indication back in August 2016. The Food and Drug Administration's decision came as part of an accelerated approval, meaning further clinical investigations are required in order to reaffirm the medication's efficacy.
The checkpoint inhibitor space may be becoming more crowded, but the fight for its top spot has consistently been between Merck & Co. and Bristol-Myers Squibb.
To be fair, Bristol-Myers has held onto it fairly tightly. Its drug Opdivo (nivolumab) has racked up similar indications to Keytruda, but raked in more than double the income last year. Opdivo revenue was $3.77 billion, whereas Keytruda sales totaled $1.4 billion.
Keytruda has made up crucial ground as of late, however. Bristol-Myers took a hard fall when its immunotherapy failed as a first-line treatment for patients with non-small cell lung cancer (NSCLC), and Merck has locked down promising clinical results and FDA go-aheads for indications that help differentiate its product, namely in urothelial bladder cancer, NSCLC and tumors with deficient mismatch repair (dMMR) systems.
And yet, what goes up must come down. Keytruda has had a rough July, with the FDA placing a clinical hold on three trials testing the drug in combination with Celgene's Revlimid (lenalidomide) or Pomalyst (pomalidomide) plus dexamethasone as a treatment for multiple myeloma.
While this latest setback doesn't appear to be deterring Merck — the company noted in the July 24 statement that other clinical trials testing Keytruda in the first-line HNSCC setting will continue as planned — it does call into question how far can a drug push the boundaries of accelerated approval conditions before the FDA takes action against it.
A similar situation is playing out with Roche's own PD-1/L1 inhibitor Tecentriq (atezolizumab), which received accelerated approval in April for locally advanced or metastatic urothelial carcinoma, yet one month later failed in Phase 3 for that same indication.
The recent developments in the space call into question whether the FDA was too optimistic about the PD-1/L1 inhibitor class and may have jumped the gun by handing out a slew of accelerated approvals before getting the complete clinical picture.