U.S. FDA Grants Breakthrough Therapy Status to Petosemtamab

Merus N.V., a clinical-stage oncology firm specializing in full-length multispecific antibodies (Biclonics® and Triclonics®), has announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for its drug candidate petosemtamab. This designation is for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) whose disease has progressed after treatment with platinum-based chemotherapy and either anti-PD-1 or anti-PD-L1 antibodies. This new designation follows the previous Fast Track Designation granted to petosemtamab in August 2023 for a similar patient population.

The BTD is based on data from an ongoing phase 1/2 open-label, multicenter clinical trial (NCT03526835) that is evaluating the efficacy and safety of petosemtamab as a monotherapy for advanced solid tumors, including previously treated HNSCC. Merus has announced its plans to provide updated data on efficacy, durability, and safety for this cohort in the latter half of 2024.

BTD is designed to expedite the development and review of drugs that show substantial improvement over existing therapies for serious or life-threatening conditions. This designation not only allows for more extensive FDA guidance but also involves senior management commitment and experienced review staff in a collaborative framework. Additionally, it offers eligibility for rolling review and priority review. Merus plans to engage in expedited discussions with the FDA to work towards a potential Biologics License Application (BLA) submission.

Ashley Pereira, Pharm.D., Senior Vice President of Regulatory Affairs at Merus, expressed enthusiasm over the BTD, stating that the designation validates petosemtamab's potential to become a new standard of care for previously treated HNSCC patients. Pereira also emphasized the company's anticipation for constructive conversations with the FDA as they prepare to initiate a phase 3 trial in mid-2024 and consider a potential phase 3 trial evaluating a combination of petosemtamab and pembrolizumab for previously untreated patients.

HNSCC describes a variety of cancers that develop in the squamous cells lining the mucosal surfaces of the mouth, throat, and larynx. These cancers are typically associated with tobacco and alcohol use, and HPV infections, varying by geographic region. HNSCC ranks as the sixth most common cancer globally, with over 930,000 new cases and more than 465,000 deaths reported in 2020. The incidence of HNSCC is expected to rise by 30%, surpassing one million new cases annually by 2030. Despite current standard treatments, HNSCC remains a serious disease with a poor prognosis.

Petosemtamab, also known as MCLA-158, is a Biclonics® low-fucose IgG1 antibody targeting both the epidermal growth factor receptor (EGFR) and the leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5). The drug exhibits three independent mechanisms of action: inhibition of EGFR-dependent signaling, LGR5 binding leading to EGFR internalization and degradation in cancer cells, and enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

Merus N.V. is dedicated to developing innovative full-length human bispecific and trispecific antibody therapeutics, known as Multiclonics®. These therapeutics are produced using industry-standard processes and demonstrate several features of conventional human monoclonal antibodies, such as long half-life and low immunogenicity.

Merus plans to continue its commitment to advancing petosemtamab through its clinical trials and towards regulatory approval, aiming to offer new hope for patients suffering from recurrent or metastatic HNSCC.