FDA has accepted Nuvalent’s NDA for neladalkib, a next‑generation ALK‑selective TKI in previously treated ALK‑positive NSCLC, granting Priority Review with a PDUFA date of November 27, 2026.
Written By: Umesh Hanumante,
M.Pharm (Reg. Affairs)
Reviewed By: Pharmacally Editorial Team
Nuvalent has reached a key regulatory milestone after the U.S. Food and Drug Administration accepted its New Drug Application (NDA) for neladalkib, an investigational ALK-selective tyrosine kinase inhibitor (TKI), in previously treated advanced ALK-positive non-small cell lung cancer (NSCLC).
The FDA granted Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) target action date of November 27, 2026.
Clinical Evidence from ALKOVE-1
The submission is supported by data from the global registrational ALKOVE-1 Phase 1/2 trial (NCT05384626), which enrolled patients with advanced ALK-positive NSCLC whose disease progressed after prior ALK inhibitor therapy. The Phase 1 portion established safety, tolerability, pharmacokinetics, and the recommended Phase 2 dose, while the ongoing Phase 2 segment carries registrational intent.
Enrollment remains ongoing in adolescents and patients with other ALK-positive solid tumors. Nuvalent said updated data from both TKI-pretreated and TKI-naïve cohorts will be presented during an oral session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.
Addressing Resistance and CNS Disease
Neladalkib is a brain-penetrant, ALK-selective inhibitor that targets resistance mutations emerging after earlier-generation ALK therapies. The molecule has shown activity against difficult-to-treat mutations, including G1202R and compound ALK resistance mutations, while sparing the structurally related TRK family to potentially reduce neurologic adverse events associated with dual TRK/ALK inhibitors.
Central nervous system metastases remain a major challenge in ALK-positive NSCLC, particularly after resistance develops to currently available TKIs. Neladalkib’s CNS activity and broad mutation coverage could help address a significant unmet need in heavily pretreated patients.
Pipeline and Corporate Expansion
Nuvalent Chief Executive Officer James Porter, Ph.D., said NDA reviews are now underway for both neladalkib and zidesamtinib, the company’s investigational ROS1-selective inhibitor. He added that the company is building commercial and medical affairs infrastructure ahead of potential launches in biomarker-driven NSCLC.
Alongside the regulatory update, Nuvalent appointed Georg Pirmin Meyer, M.D., as Chief International Officer to lead global commercialization strategy outside the United States. Meyer previously held senior leadership roles at Blueprint Medicines and Vertex Pharmaceuticals, where he oversaw European product launches and market access operations.
Regulatory Path Ahead
If approved, neladalkib could expand treatment options for patients with ALK-positive NSCLC who have progressed on multiple prior TKIs, particularly those with CNS involvement.
The milestone further positions Nuvalent as an emerging precision oncology player in biomarker-driven lung cancer.
Reference
About the Writer
Umesh Hanumante (M.Pharm) (LinkedIn) is a pharmacy professional and healthcare writer with a background in Regulatory Affairs, pharmaceutical innovation, and clinical research. He has around two years of industry experience as an Executive PMT at Troikaa Pharmaceuticals Ltd and qualified GPAT 2024. His areas of interest include regulatory compliance, dossier preparation, clinical trials, emerging therapies, and advancements in the global pharmaceutical and healthcare sector.