The FDA’s decision is backed by data from the MITIGATE trial, the first randomized, double-blind, placebo-controlled study conducted in IgG4-RD. The trial showed that UPLIZNA significantly reduced disease flares while maintaining a consistent safety profile. The approval adds a second indication to UPLIZNA, which was first cleared in 2020 for AQP4-IgG+ Neuromyelitis Optica Spectrum Disorder (NMOSD).
In addition, Amgen is continuing its efforts to expand UPLIZNA’s reach, with regulatory filings underway for generalized myasthenia gravis (gMG), for which the drug has also been granted Orphan Drug Designation. Submission for gMG approval is expected to be completed in the first half of 2025.
Aldeyra Receives FDA Complete Response Letter for Reproxalap in Dry Eye Disease
Aldeyra Therapeutics announced that the FDA has issued a Complete Response Letter (CRL) for the resubmitted NDA of reproxalap, the company’s investigational treatment for dry eye disease. While no safety or manufacturing concerns were raised, the FDA concluded that the application lacked sufficient evidence of efficacy from “adequate and well-controlled studies,” particularly in addressing ocular symptoms. The agency requested at least one additional well-controlled trial demonstrating symptom relief before reproxalap can be considered for approval.
“The CRL underscores the need to strengthen our clinical data package further,” said Todd C. Brady, M.D., Ph.D., President and CEO of Aldeyra. “Pending positive results from the ongoing clinical trials and continued dialogue with the FDA, we remain optimistic about a potential NDA resubmission by mid-2025.”
In response to prior FDA guidance, Aldeyra has been conducting three additional clinical trials—two in controlled dry eye chambers and one six-week environmental exposure trial. The company achieved the primary endpoint in one of the chamber trials in August 2024 and resubmitted the NDA in October. The remaining trial results are expected in Q2 2025, with a Type A meeting scheduled in the coming weeks to address the FDA’s latest feedback.
As of December 31, 2024, Aldeyra reported $101 million in cash, cash equivalents, and marketable securities, with most trial-related costs already incurred in 2024. The expected 2025 trial expenses are approximately $6 million, positioning the company to move forward swiftly if results support another regulatory submission.
FDA Grants Accelerated Approval to Novartis’ Vanrafia for Proteinuria in IgA Nephropathy
Novartis has received accelerated approval from the FDA for Vanrafia (atrasentan), a potent and selective endothelin A receptor antagonist, for the reduction of proteinuria in adults with primary IgA nephropathy (IgAN) who are at risk of rapid disease progression. Vanrafia, a once-daily oral therapy, can be seamlessly integrated into supportive care regimens—including use alongside RAS and SGLT2 inhibitors—with no REMS requirement, simplifying access for patients and physicians.
“Vanrafia offers a new option that can be easily added to current treatment plans, and its ability to reduce proteinuria early and consistently is critical for improving long-term outcomes in IgAN,” said Dr. Richard Lafayette, Professor of Medicine at Stanford University and Steering Committee Member for the ALIGN study. “This approval represents meaningful progress for patients who previously had limited options and faced a high risk of progressing to kidney failure.”
The approval is based on interim results from the Phase III ALIGN trial, where Vanrafia achieved a 36.1% reduction in proteinuria (P<0.0001) compared to placebo at 36 weeks, with improvement seen as early as Week 6. A similar effect was observed in patients also receiving SGLT2 inhibitors. The safety profile was favorable, though clinicians are advised to monitor liver enzymes during treatment due to class-related risks. Importantly, while the current approval is for proteinuria reduction, full approval is contingent upon results from ongoing studies evaluating Vanrafia’s impact on kidney function decline (eGFR) over 136 weeks, with data expected in 2026.
This marks Novartis’ third FDA renal approval in under a year, following FABHALTA approvals for C3G in March 2025 and IgAN in August 2024, further solidifying the company’s leadership in nephrology. Novartis is also advancing zigakibart, an anti-APRIL monoclonal antibody, currently in Phase III for IgAN, as part of its robust pipeline aimed at transforming outcomes across rare kidney diseases.
Biogen’s Tau-Targeting Therapy BIIB080 Gets FDA Fast Track for Alzheimer’s Treatment
Biogen has announced that the FDA has granted Fast Track designation to BIIB080, its investigational antisense oligonucleotide (ASO) therapy targeting tau protein, for the treatment of Alzheimer’s disease. The designation underscores the urgent need for novel approaches that can address the complex biology of this progressive and fatal neurodegenerative condition.
“We are encouraged by the FDA’s Fast Track designation for BIIB080, which highlights the urgent need for innovative treatments targeting tau pathology in Alzheimer’s disease,” said Dr. Priya Singhal, Head of Development at Biogen. “This therapy represents a differentiated approach with promising potential. We are moving forward with urgency to help patients and families affected by this devastating disease.”
BIIB080 is the first ASO therapy targeting tau to enter clinical development for Alzheimer’s and is currently being evaluated in the Phase II CELIA study, which is now fully enrolled. Previously reported Phase Ib data showed dose-dependent reductions in soluble tau in cerebrospinal fluid, decreases in aggregated tau on PET imaging, and favorable cognitive trends in exploratory outcomes—suggesting a potential clinical benefit.
With data from the CELIA trial expected in 2026, BIIB080 adds to Biogen’s diversified Alzheimer’s portfolio and reflects its commitment to advancing therapies that target distinct pathological mechanisms in the disease.
Epicrispr Receives FDA IND Clearance for EPI-321 in FSHD Treatment
Epicrispr Biotechnologies has announced FDA clearance of its Investigational New Drug (IND) application for EPI-321, a first-in-class epigenetic therapy for facioscapulohumeral muscular dystrophy (FSHD) — a rare, progressive neuromuscular disorder with no approved treatments. The clearance comes shortly after regulatory approval in New Zealand, marking a key step in the company’s global development strategy, with a Phase I/II clinical trial expected to initiate in 2025.
EPI-321 is designed as a one-time, gene-modulating therapy that uses a clinically validated AAV vector to silence the aberrant expression of the DUX4 gene, which plays a central role in FSHD by driving muscle degeneration. In preclinical models, EPI-321 showed robust DUX4 suppression and preservation of muscle tissue, supporting its potential to alter the course of the disease.
“This milestone brings new hope to people living with FSHD,” said Amber Salzman, Ph.D., CEO of Epicrispr. “EPI-321 is the first therapeutic candidate specifically designed to epigenetically silence DUX4, targeting the root cause of the disease. We’re eager to bring this innovation to the clinic and to the patients who have waited far too long for treatment options.”
The therapy has already received Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the FDA, reinforcing its potential to address a high unmet medical need.
Dr. Russell Butterfield, Associate Professor of Neurology and Pediatrics at the University of Utah, added: “EPI-321 represents a novel and promising approach in FSHD, a disorder that has long lacked effective treatment. The upcoming U.S. trial is a significant step forward for patients and their families.”
