Introduction to Subcutaneous Keytruda

MSD, known as Merck & Co. in the U.S. and Canada, has made significant strides in cancer treatment with its subcutaneous formulation of Keytruda, demonstrating comparable pharmacokinetics to the intravenous (IV) version. This breakthrough is particularly important for patients with metastatic non-small cell lung cancer (NSCLC) and other solid tumors, as it offers a more convenient administration method without sacrificing efficacy. Keytruda, or pembrolizumab, is an immunotherapy medication that works by enhancing the body's immune response to cancer cells.

Clinical Trial Outcomes for Subcutaneous Keytruda

The pivotal 3475A-D77 Phase 3 trial compared the subcutaneous Keytruda, co-administered with berahyaluronidase alfa, to the traditional IV form, both in combination with chemotherapy for NSCLC patients. The trial met its primary endpoints by showing noninferior pharmacokinetics for the subcutaneous version compared to the IV form. Specifically, Keytruda SC was noninferior in terms of overall drug exposure during the first cycle and steady-state trough concentrations during the third cycle. Notably, the geometric mean ratios for these measurements were above expectations, indicating higher concentrations for the SC formulation[1][2][3].

Key Findings:

• Pharmacokinetics: Subcutaneous Keytruda demonstrated noninferior pharmacokinetics compared to IV Keytruda.
• Efficacy: Both formulations showed similar efficacy with comparable rates of disease progression or death, though survival data slightly favored the subcutaneous version[1][3].
• Safety Profile: The safety profiles of both formulations were consistent, with similar rates of Grade 3 or higher adverse events[2][3].
• Administration Time: Subcutaneous injections took a median of two minutes, significantly shorter than the 30 minutes required for IV infusions[5].

Benefits of Subcutaneous Administration

The subcutaneous formulation offers several benefits over the IV version:

• Convenience: Faster administration reduces patient and healthcare provider time, enhancing the treatment experience[2][3].
• Efficacy and Safety: Comparable to IV Keytruda in both efficacy and safety, ensuring that patients receive effective treatment with fewer logistical hurdles[2][3].
• Future Potential: Expected to increase access and treatment adherence due to its ease of administration[1].

Regulatory Status and Future Plans

Following the successful trial results, the U.S. FDA has accepted a Biologics License Application (BLA) for subcutaneous Keytruda, aiming to cover all existing solid tumor indications for the IV form, with a target approval date set for September 23, 2025[2][3]. The European Medicines Agency (EMA) has also validated an extension application for this new pharmaceutical form[3].

Challenges Ahead

Despite the clinical success, Merck faces legal challenges from Halozyme Therapeutics, which alleges that the human hyaluronidase enzyme used in subcutaneous Keytruda infringes on its patents. Merck has initiated a patent challenge process and seeks to resolve the issue to secure commercialization rights[1].

Market Impact and Competitors

The subcutaneous formulation of Keytruda joins other cancer drugs like Tecentriq and Opdivo in offering a more convenient delivery method. This innovation positions MSD competitively in the oncology market, potentially expanding its market share by providing a preferred option for patients requiring long-term treatments.

Key Competitors:

• Tecentriq (Roche): Already offers a subcutaneous formulation approved by the FDA.
• Opdivo (Bristol Myers Squibb): Also has a subcutaneous version available.

Conclusion

MSD's development of subcutaneous Keytruda represents a significant advancement in cancer treatment, promising a more convenient and efficient delivery method without compromising efficacy. As the regulatory approval process unfolds, this formulation is poised to enhance patient care and improve healthcare outcomes for those affected by solid tumors.