Glenmark Pharmaceuticals has received regulatory approval from India's Drugs Controller General of India (DCGI) to initiate a pivotal multi-country Phase 3 clinical trial for Envafolimab, a novel subcutaneous PD-L1 inhibitor, in patients with resectable Stage III non-small cell lung cancer (NSCLC). The approval marks a significant milestone in expanding access to innovative immunotherapy for one of the most challenging stages of lung cancer treatment.
Global Trial Expansion Underway
The randomized, multi-center Phase 3 trial will assess the efficacy, safety, pharmacokinetics, and immunogenicity of Envafolimab in patients with resectable Stage IIIA and IIIB (N2) NSCLC. Beyond India, Glenmark has submitted a Clinical Trial Application in Russia and is preparing to open additional clinical trial sites in Brazil and Mexico, significantly expanding the global footprint of this pivotal study.
This international expansion complements an ongoing parallel Phase 3 study of Envafolimab sponsored by 3D Medicines Inc., which was initiated in December 2023 and is actively recruiting patients in China.
Addressing Critical Unmet Medical Need
The trial targets a significant gap in cancer treatment, as lung cancer remains the leading cause of cancer-related deaths worldwide. NSCLC comprises approximately 80-85% of all lung cancer cases, with 20-30% diagnosed at Stage III. Despite surgical options available for a subset of Stage III patients, five-year survival rates remain disappointingly low, ranging from 36% for Stage IIIA and 26% for Stage IIIB patients.
"The initiation of this pivotal Phase 3 study for Envafolimab marks an important milestone in Glenmark's journey to reimagine possibilities in oncology," said Dr. Monika Tandon, Global Head of Clinical Development at Glenmark Pharmaceuticals Limited. "With its novel subcutaneous administration, Envafolimab has the potential to make cutting-edge immunotherapy more accessible and convenient for patients worldwide, especially in regions where healthcare resources are constrained."
Novel Subcutaneous Delivery Mechanism
Envafolimab represents a breakthrough in immunotherapy administration as a recombinant single domain anti-PD-L1 fused with the Fc portion of human IgG1, designed for subcutaneous delivery. The drug was originally invented by Alphamab Oncology and co-developed with 3D Medicines Inc. since 2016.
The subcutaneous formulation offers significant practical advantages, allowing for administration within 30 seconds like a regular subcutaneous injection. This rapid delivery method has the potential to reduce the burden on patients, caregivers, and healthcare systems compared to traditional intravenous immunotherapy approaches.
Proven Clinical Success in China
Envafolimab has already demonstrated clinical success, receiving approval from China's National Medical Products Agency (NMPA) in November 2021 as the world's first subcutaneous anti-PD-L1 therapy. The drug is approved for treating advanced unresectable or metastatic solid tumors with MSI-H/dMMR and has been included in the NMPA's 'List of breakthrough therapies.'
More than 40,000 cancer patients in China have already benefited from this innovative drug, providing substantial real-world evidence of its therapeutic potential and safety profile.
Expanding Development Pipeline
Currently, Envafolimab is undergoing clinical development in multiple Phase 2 and Phase 3 trials for various tumor types, including resectable non-small cell lung cancer, advanced/metastatic biliary tract cancer, metastatic endometrial cancer, and renal cell cancer.
In 2024, Alphamab Oncology and 3D Medicines Inc. entered into a licensing agreement with Glenmark Pharmaceuticals, granting Glenmark exclusive rights for development, registration, and commercialization of oncology indications of Envafolimab across India, Asia Pacific (except Singapore, Thailand, Malaysia), the Middle East and Africa, Russia, Commonwealth of Independent States, and Latin America.
Market Response
The announcement generated positive investor sentiment, with Glenmark Pharmaceuticals' shares surging 3% to Rs 2,050.70 on the National Stock Exchange following the regulatory approval news, reflecting market confidence in the company's oncology pipeline advancement.
