Top 7 Late-Stage Investigational Drugs Advancing Towards FDA Approval in 2025

In 2025, the pharmaceutical industry is continuing to advance through focused innovation, driven by several late-stage investigational drugs moving toward FDA review. Phase 3 trials remain a critical benchmark for evaluating efficacy, safety, and clinical benefit across diverse patient populations. In the first half of 2025, multiple therapies targeting a variety of disorders progressed through this pivotal stage, highlighting the sector’s ongoing commitment to addressing unmet medical needs via evidence-based development.

Below is an overview of the investigational drugs progressing towards approval in 2025.

1. Crinetics Pharmaceuticals’ Paltusotine Progresses Toward FDA Clearance

Crinetics Pharmaceuticals, Inc. is advancing paltusotine, a once-daily, oral selective somatostatin receptor type 2 (SST2) nonpeptide agonist, as a treatment for acromegaly. The FDA is reviewing the New Drug Application (NDA), with a PDUFA (Prescription Drug User Fee Act) target date of September 25, 2025. Clinical trials have shown rapid and durable insulin-like growth factor 1 (IGF-1) regulation in surgically naïve patients. The European Medicines Agency (EMA) has validated the Marketing Authorization Application. According to EMR estimates, the global acromegaly treatment market is projected to grow at a CAGR of 7.70% between 2025-2034. The company’s pipeline also includes atumelnant for congenital adrenal hyperplasia and ACTH-dependent Cushing’s syndrome, supported by USD 1.2 billion in cash, funding ongoing global development and late-stage trials.

2. Epioxa™ Receives FDA NDA Acceptance for Keratoconus Management

Epioxa™ (Epi-on) by Glaukos Corporation is a non-invasive corneal cross-linking therapy for keratoconus, a progressive corneal disorder that threatens vision. The FDA accepted Epioxa’s NDA in February 2025, with a PDUFA goal date of October 20, 2025. Two pivotal Phase 3 trials demonstrated statistically significant reductions in maximum corneal curvature (Kmax) and confirmed a favorable safety and tolerability profile. Developed and funded by Glaukos, the therapy combines a bio-activated formulation with UV-A light and supplemental oxygen to halt disease progression. Its approval in 2025 would establish the first FDA-approved non-invasive therapy for keratoconus.

3. Mucopolysaccharidosis II Drug by Regenxbio Advances as One-Time Gene Therapy

In May 2025, Regenxbio Inc. received FDA acceptance and Priority Review of its Biologics License Application (BLA) for clemidsogene lanparvovec (RGX-121), a one-time gene therapy targeting Mucopolysaccharidosis II (MPS II), a rare X-linked lysosomal disorder causing systemic and neurological complications. RGX-121 utilizes an adeno-associated viral vector to deliver the iduronate-2-sulfatase (IDS) gene to the central nervous system, enabling durable enzyme expression and cellular cross-correction. A strategic partnership with Nippon Shinyaku provides USD 110 million upfront and up to USD 700 million in milestone payments; REGENXBIO manages manufacturing and retains Priority Review Voucher rights. The therapy holds multiple regulatory designations, including Orphan Drug, RMAT, and Fast Track, with a PDUFA date of November 9, 2025.

4. FDA Grants Priority Review to Ziftomenib for NPM1-Mutant AML

Kura Oncology and Kyowa Kirin have secured FDA acceptance and Priority Review for their NDA of ziftomenib in adults with relapsed or refractory NPM1-mutant acute myeloid leukemia (AML), targeting a PDUFA action date of November 30, 2025. Ziftomenib, an oral menin inhibitor, achieved statistically significant complete remission (CR) and CR with partial hematologic recovery (CRh) in the Phase 2 KOMET-001 trial, with minimal myelosuppression and only 3% treatment-related discontinuations. By selectively inhibiting the menin pathway, ziftomenib addresses multiple AML genetic alterations. Supported by breakthrough therapy, fast track, and orphan drug designations, it represents a promising option for patients with high unmet medical needs.

5. Sibeprenlimab Receives FDA Priority Review for IgA Nephropathy

Otsuka Pharmaceutical has announced FDA acceptance and priority review of its BLA for sibeprenlimab, a monoclonal antibody for immunoglobulin A nephropathy (IgAN), a progressive autoimmune kidney disease. The therapy carries a Breakthrough Therapy designation and a PDUFA action date of November 28, 2025. Sibeprenlimab selectively inhibits APRIL, reducing galactose-deficient IgA1 production and immune complex deposition in the kidneys. Interim Phase 3 VISIONARY trial results showed a 51.2% reduction in 24-hour urine protein-to-creatinine ratio over nine months. The therapy is designed as a single-dose prefilled syringe for subcutaneous administration every four weeks, improving patient convenience.

6. Aldeyra Therapeutics Gains FDA NDA Review for Dry Eye Disease

In July 2025, Aldeyra Therapeutics obtained FDA acceptance for its NDA for reproxalap, targeting the signs and symptoms of dry eye disease. According to the EMR Report, the dry eye disease market is expected to grow at a CAGR of 6.50% during the 2025-2034 period. In a Phase III trial with around 116 patients, reproxalap achieved its primary endpoint by significantly reducing ocular discomfort versus vehicle control. This first-in-class small-molecule RASP modulator targets elevated RASP levels linked to ocular inflammation, demonstrating efficacy and a favorable safety profile in over 2,900 patients. Self-funded and focused on immune-modulating therapies, Aldeyra aims for potential FDA approval by the PDUFA date of December 16, 2025.

7. Aficamten Targets Obstructive Hypertrophic Cardiomyopathy with Review Set for December 26, 2025

Cytokinetics has developed aficamten, a cardiac myosin inhibitor, for obstructive hypertrophic cardiomyopathy (oHCM), characterized by thickened heart muscle and reduced cardiac function. Aficamten’s NDA is under FDA review, with a PDUFA date of December 26, 2025, following submission of a REMS. In the Phase 3 SEQUOIA-HCM trial with 282 symptomatic patients, aficamten significantly improved peak oxygen uptake, symptom severity, and cardiac performance. Backed by over USD 1 billion in internal funding and strategic partnerships, aficamten enhances cardiac output and reduces obstruction, supporting potential U.S. approval.

These investigational drugs illustrate the breadth of late-stage clinical innovation, targeting conditions ranging from rare genetic disorders and ocular diseases to hematologic malignancies, autoimmune kidney disorders, dry eye disease, and cardiovascular conditions. As these therapies advance toward potential FDA approval, they underscore the industry’s commitment to precision medicine, patient-centric solutions, and addressing unmet healthcare needs. Additional disease-focused therapies are expected to enter pivotal trials and regulatory review throughout 2025.