Novel Therapies to Watch in 2025: Oncology, Hematology, and Neurology
Key Insights
Tarlatamab (Imdelltra) is set to transform small cell lung cancer (search) treatment, targeting DLL3 (search)-expressing cells and potentially becoming the standard of care for previously treated ES-SCLC.
Fitusiran, an antithrombin-targeting siRNA, offers a novel approach to hemophilia A (search) or B treatment, demonstrating significant reductions in annualized bleeding rates in phase 3 trials.
Vepdegestrant (ARV-471), a PROTAC protein degrader, shows promise in ER+ (search)/HER2- (search) metastatic breast cancer, potentially offering a more effective protein degradation mechanism.
Several new drugs are poised to make a significant impact across oncology, hematology, and neurology in 2025, offering new therapeutic options for a multitude of diseases. These therapies, highlighted for their innovative mechanisms and promising clinical trial results, are expected to address unmet needs and improve patient outcomes.
Tarlatamab (Imdelltra; Amgen) for Small Cell Lung Cancer
Tarlatamab, granted FDA approval in May 2024, is set to revolutionize the small cell lung cancer (search) (SCLC) treatment landscape. Approved as a bi-weekly intravenous infusion for adults with extensive-stage SCLC who have progressed on or after platinum-based chemotherapy, tarlatamab works by binding to DLL3 (search) on tumor cells and CD3 on T-cells, facilitating the elimination of DLL3-expressing SCLC cells. This bispecific T cell engager molecule, developed by Amgen, offers a novel approach to treating this aggressive cancer.
Given the typically poor prognosis associated with SCLC and the limited treatment options beyond chemotherapy, tarlatamab's approval, following significantly positive results from the DeLLphi-301 study, positions it as a potential standard of care for previously treated extensive-stage SCLC in 2025.
Fitusiran (Alnylam Pharmaceuticals, Sanofi) for Hemophilia A or B
Fitusiran, an antithrombin-targeting small interfering RNA (siRNA), is designed for subcutaneous administration, either monthly or bi-monthly, as a prophylactic treatment for hemophilia A (search) or B, regardless of inhibitor status. This innovative RNA interference therapy selectively down-regulates specific genes to better target complex diseases.
Clinical trial data from completed phase 3 studies indicate that fitusiran leads to meaningful reductions in annualized bleeding rate (ABR) in patients with hemophilia A (search) or B. In the ATLAS-A/B trial, involving 120 participants with hemophilia A or B without inhibitors, once-monthly administration of fitusiran resulted in an 89.9% reduction in ABR compared to those receiving on-demand factor concentrate. Furthermore, the ATLAS-INH trial demonstrated the superiority of fitusiran over an on-demand bypass agent, showing a 90.8% reduction in ABR over 9 months. Expected to launch in March 2025, fitusiran offers a new, effective, and convenient option for patients with hemophilia A or B.
Vepdegestrant (ARV-471; Arvinas, Pfizer) for ER+/HER2- Breast Cancer
Vepdegestrant, an orally administered treatment for adults with estrogen receptor (search) (ER)-positive/HER2-negative locally advanced or metastatic breast cancer, has the potential to make a significant impact in the ER+ (search)/HER2- (search) breast cancer space. It could become the first PROteolysis Targeting Chimera (PROTAC) protein degrader to receive regulatory approval. The treatment is designed to degrade the ER protein, and early trial results suggest that the PROTAC-based mechanism of action behind vepdegestrant makes protein degradation effective and complete compared with oral selective estrogen receptor degraders (SERDs).
Phase 3 trials examining vepdegestrant's safety and efficacy are ongoing, with results from phase 1b and phase 2 of the VERITAC clinical trial already reported. In phase 1b, vepdegestrant demonstrated efficacy in patients with at least one prior line of endocrine therapy and no more than two lines of chemotherapy in the metastatic setting. Furthermore, the phase 2 cohort expansion of VERITAC showed the medicine was effective and led to strong progression-free survival in patients who had received CDK4/6 inhibitors in the metastatic setting. Continued development of vepdegestrant will allow for further analysis in other patient populations as it prepares to launch in 2025.
Cobenfy (Xanomeline and Trospium Chloride; Karuna Therapeutics) for Schizophrenia
A novel combination of xanomeline and trospium chloride, Cobenfy (formerly KarXT) is a twice-daily oral treatment for adults with schizophrenia (search) and is in development for patients with inadequate response to schizophrenia and psychosis related to Alzheimer's disease (AD). It received FDA approval in September 2024 for the treatment of adults with schizophrenia, becoming the first in a new class by selectively targeting the M1 and M4 receptors in the brain, while not blocking the dopamine D2 receptors.
Many existing schizophrenia (search) treatments target D2 receptor signaling, which makes it difficult for every patient to find an effective treatment. In the EMERGENT clinical trial program, Cobenfy demonstrated improvements in the total Positive and Negative Syndrome Scale score in patients with schizophrenia, with treatment effects observed for some patients as early as 2 weeks. Its potential success in reducing psychosis related to AD makes this new treatment one to watch throughout 2025.
Zanzalintinib (XL092; Exelixis)
A tyrosine kinase (TK) inhibitor that targets vascular endothelial growth factor (VEGF (search)), zanzalintinib is a once daily, orally administration drug currently under investigation in non-clear-cell renal cell carcinoma (search) (nccRCC), colorectal cancer (search) (CRC), and squamous cell carcinoma of the head and neck (search) (SCCHN), with an expected launch in the US of 2026. According to Clarivate experts, it is designed to target the activity of receptor TKs that feature in tumor angiogenesis, metastasis, and immunosuppression.
Zanzalintinib is currently being examined in a series of phase 3 trials in combination with other immune checkpoint inhibitors. The drug has potential to offer a new treatment option specifically for the non-clear-cell histology if approved, easing the disease burden for patients in this population who may struggle to find an effective treatment. Zanzalintinib’s half-life supports administration once daily, which could lead to more favorable tolerability and better adherence among prescribed patients.