Keytruda Fails Again in Phase III Endometrial Cancer Trial

Merck’s blockbuster immunotherapy, Keytruda, has faced another setback in its ongoing battle to treat endometrial cancer. On Thursday, the pharmaceutical giant disclosed that Keytruda failed to meet the primary endpoint in a Phase III trial for high-risk endometrial cancer patients when used as an adjuvant treatment with chemotherapy, with or without radiotherapy. The primary endpoint was disease-free survival compared to a placebo, and the interim analysis revealed that the treatment did not achieve the desired outcome.

Keytruda is already approved for use in certain types of endometrial cancer. It can be administered in combination with Eisai’s Lenvima for advanced, inoperable endometrial carcinoma that has progressed after prior therapy, as well as a single agent for similarly diagnosed patients. Additionally, Merck has been conducting a development program to test Keytruda's efficacy in combination with chemotherapy and as a standalone treatment in specific patient populations.

However, this is not the first time Keytruda has encountered challenges in treating endometrial cancer. In December 2023, a combination of Keytruda and Lenvima failed to enhance survival rates in patients with advanced or recurrent endometrial carcinoma. This recent string of failures has cast a shadow over Keytruda’s performance in clinical trials.

Keytruda has also faced difficulties outside of endometrial cancer. In December, Merck reported that a combination of Keytruda and its experimental anti-TIGIT antibody, vibostolimab, did not improve progression-free survival in patients with non-small cell lung cancer (NSCLC). On the same day, a trial testing Keytruda in combination with AstraZeneca’s Lynparza did not demonstrate significant improvements in overall survival for patients with metastatic squamous NSCLC. In March, another trial showed that the Keytruda-Lynparza combination fell short of its dual primary endpoints in patients with metastatic non-squamous NSCLC.

Despite these setbacks, Keytruda remains a high-performing drug for Merck. Since its approval in 2014 for advanced melanoma patients with a BRAF mutation, Keytruda has secured over 30 indications. Its commercial success is evident from the financial figures. In April, Merck reported a 20% increase in Keytruda sales for the first quarter of 2024 compared to the same period the previous year. The treatment generated $6.9 billion in revenue for the quarter, making up almost half of Merck’s $14 billion in total pharmaceutical sales. Analysts project that Keytruda could achieve annual sales exceeding $30 billion by 2026. However, the drug is expected to face competition from biosimilars as soon as 2028, which could impact its sales significantly.

Overall, while Keytruda continues to be a major revenue driver for Merck, its recent clinical trial failures highlight the challenges and uncertainties that come with developing treatments for complex diseases like endometrial cancer and NSCLC. The pharmaceutical industry will be closely watching Merck’s next steps as it navigates these hurdles and seeks to maintain Keytruda’s market-leading position.