“The FDA’s Orphan Drug Designation for RAG-21 underscores the urgent need for innovative therapies for ALS, particularly for FUS mutations,” said Dr. Long-Cheng Li, Founder and CEO of Ractigen Therapeutics. “FUS-ALS is one of the most severe and rapidly progressing subtypes, and no curative treatments currently exist.”
Dr. Li emphasized the company’s broader mission, adding, “We are committed to advancing breakthrough therapies like RAG-21 to provide meaningful options for patients suffering from ALS and other life-threatening rare diseases.”
Intellia Therapeutics Secures FDA RMAT Designation for Nexiguran Ziclumeran for Hereditary ATTR Amyloidosis
Intellia Therapeutics, Inc. announced that the FDA has granted nexiguran ziclumeran (nex-z, also known as NTLA-2001) regenerative medicine advanced therapy (RMAT) designation. This investigational in vivo CRISPR therapy targets hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) by inactivating the TTR gene, preventing TTR protein production, and addressing the disease’s underlying cause. Nex-z is part of Intellia’s multi-target collaboration with Regeneron.
The RMAT designation follows interim Phase I data showing that nex-z provides rapid, deep, and durable reductions in TTR protein levels, potentially halting or reversing ATTRv-PN. This recognition adds to two previous regulatory designations for nex-z: Orphan Drug Designation from the U.S. FDA and European Commission.
“This RMAT designation highlights the transformative potential of nex-z for patients with ATTRv-PN,” said Dr. John Leonard, President and CEO of Intellia. “We are committed to working with the FDA to accelerate its development and bring this one-time, paradigm-shifting treatment to patients as soon as possible.”
The RMAT pathway, established under the 21st Century Cures Act, facilitates the review of promising therapies for serious or life-threatening diseases. Benefits include early FDA interactions, discussions on endpoints supporting accelerated approval, and potential priority review of the biologics license application (BLA).
FDA Approves Acoramidis (Attruby) for ATTR-CM
The FDA has approved Acoramidis (Attruby) for treating transthyretin amyloid cardiomyopathy (ATTR-CM) in adults. This first-line therapy is designed to reduce cardiovascular deaths and related hospitalizations. Developed by BridgeBio Pharma, Acoramidis is the first approved drug with a label specifying near-complete (≥90%) transthyretin (TTR) stabilization, offering new hope for managing this previously fatal condition. The approval follows findings from the ATTRibute-CM Phase III trial, which demonstrated significant benefits in reducing all-cause mortality and cardiovascular hospitalizations compared to placebo.
The ATTRibute-CM trial included 632 participants, most of whom were men aged 77.6 years on average, with the majority having wild-type TTR. The study found that Acoramidis reduced all-cause mortality and cardiovascular hospitalizations by 42% over 30 months. The trial’s hierarchical analysis also highlighted improvements in biomarkers and functional outcomes, including NT-proBNP levels and 6-minute walking distances, further supporting the therapy’s efficacy and safety.
“Transthyretin cardiac amyloidosis is a progressive disease with a dire prognosis when untreated,” said Dr. Martha Grogan of the Mayo Clinic. “Having a first-line treatment like Attruby that provides excellent TTR stabilization and improved outcomes gives patients hope. The data indicates reduced mortality and hospitalizations as early as three months after starting therapy, transforming this once-fatal disease into a manageable chronic condition.”
Muriel Finkel, President of Amyloidosis Support Groups, emphasized the significance of this approval. “The FDA approval of Attruby is a major milestone for the amyloidosis community. Access to this therapy provides new hope and opportunities for patients living with ATTR-CM, improving their quality of life and outcomes.”
Jazz Pharmaceuticals Gains FDA Approval for Ziihera for HER2-positive Biliary Tract Cancer
The FDA has granted accelerated approval to Jazz Pharmaceuticals’ Ziihera (zanidatamab-hrii) for the treatment of adults with previously treated, unresectable, or metastatic HER2-positive biliary tract cancer (BTC). The approval is based on data from the HERIZON-BTC-01 trial, which reported a 52% objective response rate (ORR) and a median duration of response (DOR) of 14.9 months. Ziihera is the first dual HER2-targeted bispecific antibody and chemotherapy-free treatment option for HER2-positive BTC. Continued approval is contingent upon the results of the ongoing Phase III HERIZON-BTC-302 trial, which is evaluating Ziihera in combination with standard therapy in the first-line setting.
The HERIZON-BTC-01 trial, the largest Phase IIb study for this patient population, demonstrated significant efficacy and safety in 62 patients with HER2-positive BTC. Data presented at major conferences, including ASCO, highlighted Ziihera’s ability to meet its primary endpoint of confirmed ORR, offering a promising new treatment option for this challenging cancer type. The safety profile revealed manageable adverse effects, including diarrhea, fatigue, and biliary complications, with serious adverse reactions reported in 53% of participants.
Rob Iannone, M.D., EVP and Chief Medical Officer at Jazz Pharmaceuticals, emphasized the significance of Ziihera’s approval: “BTC has a devastating prognosis, and HER2-positive cases have had few options. This approval provides an important advance for patients and underscores our commitment to improving outcomes in HER2-expressing cancers.” Dr. James Harding from Memorial Sloan Kettering Cancer Center echoed this sentiment, highlighting the drug’s antitumor activity and its potential as a new therapeutic option for BTC patients.
Stacie Lindsey, CEO of the Cholangiocarcinoma Foundation, spoke to the impact of Ziihera’s approval on patients and families. “Metastatic BTC profoundly affects patients’ lives and well-being. Ziihera offers the possibility of more time and improved quality of life, a critical step forward for the BTC community.” The ongoing trials in other cancers, including gastroesophageal adenocarcinomas and metastatic breast cancer, reflect Jazz Pharmaceuticals’ broader commitment to advancing HER2-targeted therapies.
Johnson & Johnson has submitted a supplemental Biologics License Application (sBLA) to the FDA, seeking approval for a subcutaneous induction regimen of TREMFYA® (guselkumab) to treat adults with moderately to severely active ulcerative colitis (UC). This filing builds on the recent approval of TREMFYA® for UC, where it is currently administered via intravenous induction followed by subcutaneous maintenance. The submission is based on data from the Phase III ASTRO study, which evaluated a 400 mg SC induction dose administered at Weeks 0, 4, and 8, demonstrating statistically significant and clinically meaningful clinical remission rates by Week 12.
The ASTRO study also met all secondary endpoints, including endoscopic improvement and histologic-endoscopic mucosal improvement (HEMI). Safety data were consistent with findings from the QUASAR program, supporting the therapy’s safety and efficacy profile. TREMFYA® is a dual-acting monoclonal antibody targeting IL-23, a key cytokine in immune-mediated diseases like UC, making it the first in its class to potentially offer both intravenous and subcutaneous induction options for this condition.
Dr. Esi Lamousé-Smith, Vice President and Gastroenterology Disease Area Lead at Johnson & Johnson, emphasized the importance of this milestone. “With the ASTRO study in UC and the GRAVITI study in Crohn’s disease, we aim to deliver versatile treatment options for inflammatory bowel disease. TREMFYA has the potential to be the first IL-23 inhibitor offering a fully subcutaneous induction and maintenance regimen, bringing choice and simplicity to patients and providers,” she stated. She also highlighted that the ASTRO data builds on the promising results seen in the QUASAR program, reinforcing TREMFYA’s role in transforming outcomes for patients with inflammatory bowel disease.
The company also noted that TREMFYA®’s dual-acting mechanism and ability to block IL-23 positions it as a leading innovation in UC treatment. If approved, this subcutaneous induction regimen would provide a new level of convenience, addressing the needs of patients and healthcare providers alike. Johnson & Johnson continues to pursue regulatory approvals for TREMFYA® in other conditions, including Crohn’s disease, further cementing its commitment to advancing treatment options for immune-mediated diseases.
