GSK has established a renewed commitment to cancer treatment, prioritizing the discovery and development of specialty medicines. The company’s oncology strategy leverages expertise in immunology, human genetics, and advanced technologies to create targeted therapies. This involves commercializing approved treatments and investing in novel research platforms and a robust developmental pipeline. GSK concentrates efforts on areas of high unmet patient need, such as gynecologic and hematologic cancers, aiming to intervene earlier and maximize long-term survival for patients globally.
Defining GSK’s Current Approved Portfolio
GSK’s commercial oncology portfolio is built upon precision medicine, matching therapies to specific molecular or genetic characteristics of a patient’s tumor.
Niraparib
Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor marketed for treating certain types of ovarian cancer. This drug exploits synthetic lethality by blocking a DNA repair pathway that cancer cells rely on when they have a defect in another repair pathway, such as a BRCA gene mutation. Inhibiting PARP causes irreparable DNA damage, leading to the selective death of the tumor cells.
Dostarlimab
Another important therapy is dostarlimab, a programmed death receptor-1 (PD-1) blocking antibody. This immunotherapy is approved for treating specific recurrent or advanced endometrial cancers that are mismatch repair-deficient (dMMR). Dostarlimab works as a checkpoint inhibitor, allowing the body’s T-cells to recognize and attack the cancer. This mechanism is effective in tumors with high microsatellite instability (MSI-H).
Momelotinib
The portfolio also includes momelotinib, approved for treating intermediate or high-risk myelofibrosis, a type of blood cancer. This drug acts as a Janus kinase (JAK) 1 and JAK2 inhibitor, targeting the dysregulated signaling pathways often found in this disease. Momelotinib also inhibits ACVR1, which helps address anemia, a common symptom for many patients with myelofibrosis.
Strategic Research Focus Areas
GSK’s research and development strategy focuses on three interconnected scientific platforms designed to generate the next generation of cancer treatments.
Immuno-Oncology
This platform seeks to harness the body’s immune system to fight malignant cells. GSK is exploring novel checkpoint targets, such as T-cell Immunoreceptor with Ig and ITIM domains (TIGIT) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3). These next-generation antibodies aim to overcome immune suppression within the tumor microenvironment, potentially offering new options for patients who do not respond to existing immunotherapies.
Synthetic Lethality
This area builds on the mechanism of action seen in the approved PARP inhibitor. Researchers are investigating other vulnerabilities in cancer cells that arise from defects in DNA damage repair (DDR) or cellular metabolism pathways. The goal is to develop drug combinations that are lethal only to the cancer cell due to its pre-existing genetic weaknesses. This selective approach maximizes anti-tumor activity while sparing healthy tissue.
Tumor Cell Targeting
This focus area encompasses advanced modalities like Antibody-Drug Conjugates (ADCs) and T-cell engagers. ADCs link a potent chemotherapy agent to an antibody, allowing the drug to be delivered directly to cancer cells expressing a particular surface protein. T-cell engagers are designed to physically bridge a patient’s T-cells to a tumor cell, activating the T-cell to destroy the cancer. These platforms translate genetic and immune insights into therapeutic compounds.
Key Developmental Pipeline
GSK’s late-stage pipeline advances both novel molecules and the expansion of existing approved therapies into new indications or combinations.
Novel Assets
Belantamab mafodotin, an Antibody-Drug Conjugate (ADC) targeting B-cell maturation antigen (BCMA), is a significant asset in development for relapsed/refractory multiple myeloma (RRMM). This drug delivers a cytotoxic agent directly to myeloma cells that express BCMA, illustrating the Tumor Cell Targeting strategy. Clinical trials are exploring its use in earlier lines of therapy and in combination with other agents to improve outcomes for this hematologic cancer.
Pipeline Expansion
Niraparib is currently being studied in a Phase 3 trial for glioblastoma, an aggressive type of brain cancer. This effort extends the Synthetic Lethality strategy beyond ovarian cancer to address a tumor type with limited treatment options. Furthermore, dostarlimab is undergoing Phase 3 trials in combination with chemotherapy for patients with primary advanced or recurrent endometrial cancer, seeking to move the immunotherapy into a first-line setting.
Next-Generation Immuno-Oncology
The pipeline also includes novel immunotherapies like belrestotug (anti-TIGIT antibody) and cobolimab (anti-TIM-3 antibody). These are being investigated in combination with dostarlimab for various solid tumors, including non-small cell lung cancer (NSCLC) and head and neck cancer. These combination studies test the hypothesis that blocking multiple immune checkpoints simultaneously can lead to a deeper and more durable anti-tumor response.