The FDA has halted clinical testing of an Intellia Therapeutics gene-editing therapy following a report that a patient in a Phase 3 study was hospitalized with liver complications.
Intellia said the liver problems met the trial protocol’s criteria for pausing the studies, which the company did on Monday. The therapy, nexiguran ziclumeran, or nex-z, is an experimental treatment for the rare disease transthyretin amyloidosis (ATTR). According to Intellia, the injured patient received nex-z on Sept. 30. On Oct. 24, this patient developed high levels of liver enzymes and compounds indicative of damage to the organ. Intellia said the FDA on Wednesday verbally notified the company that the two Phase 3 tests of the experimental therapy are now under a clinical hold.
In ATTR, misfolded versions of the liver protein transthyretin (TTR) lead to accumulation of amyloid protein in tissues, causing problems in the body. Nex-z uses the CRISPR gene-editing technology to inactivate the gene that codes for TTR protein. Nex-z had advanced to two Phase 3 tests, one for ATTR cardiomyopathy and the other for ATTR polyneuropathy. The patient who developed liver complications was in the cardiomyopathy study.
New ATTR drugs are gaining traction in the market. While Pfizer drugs Vyndaqel and Vyndamax are established as standard ATTR cardiomyopathy treatments, FDA approvals in the past year for BridgeBio Pharma’s Attruby and Alnylam Pharmaceuticals’ Amvuttra bring patients additional options. Amvuttra was first approved for ATTR polyneuropathy in 2022.
The ATTR drugs currently available are chronic treatments. Intellia’s nex-z offers the potential for a one-time treatment. The company is developing nex-z under a partnership with Regeneron Pharmaceuticals. Intellia leads clinical development of nex-z while Regeneron holds an option to co-commercialize the therapy in the U.S.
The FDA told Intellia a formal clinical hold letter for nex-z’s Phase 3 studies would be issued within 30 days. In the meantime, the company said it intends to work with the agency “to address the clinical hold as expeditiously as possible.”
Here’s a recap of other recent regulatory developments:
FDA and EU Regulatory Approvals
—GSK multiple myeloma drug Blenrep is returning to the market. Three years ago, the pharma giant withdrew the antibody drug conjugate after it failed its confirmatory study as a monotherapy. GSK’s resubmission is based on Phase 3 tests of the drug in combination with standard therapies and as an earlier line of treatment. While these studies were successful, the FDA approved Blenrep as a third-line or later multiple myeloma treatment. The drug’s European approval permits its use as a second-line therapy.
—The FDA approved Bayer’s Lynkuet as a treatment for moderate-to-severe vasomotor symptoms of menopause. The oral small molecule inhibits the NK1 and NK3 receptors, both of which regulate body temperature. Lynkuet will compete against Astellas Pharma’s menopause drug Veozah, which blocks the NK3 receptor.
—Boehringer Ingelheim drug Jascayd received FDA approval for treating adults with idiopathic pulmonary fibrosis, a chronic and ultimately fatal lung disorder. The twice-daily pill offers a different mechanism of action than Ofev, an older Boehringer IPF drug that’s a blockbuster seller.
—Rhapsido, a BTK inhibitor discovered and developed by Novartis, landed FDA approval for treating chronic spontaneous urticaria, an inflammatory skin disorder that leads to chronic hives. The regulatory decision covers use of the twice-daily pill by patients whose disease does not respond to treatment with first-line treatment with antihistamines.
—The FDA approved Crinetics’s Palsonify as a first-line treatment for acromegaly, a rare endocrine disorder. The once-daily pill offers an oral alternative to blockbuster drugs from Novartis and Ipsen that are administered as injections.
—The FDA approved Keytruda Qlex, an injectable version of the Merck immunotherapy Keytruda. The regulatory decision covers nearly all of the cancer indications covered by the original intravenously infused product. Keytruda Qlex is administered as a subcutaneous injection that takes two minutes or less compared to the half hour required for a Keytruda infusion.
—Kedrion Biopharma landed FDA approval for Qivigy for the treatment of adults with primary humoral immunodeficiency, a group of disorders that compromise immune system function. The drug is an intravenous immunoglobulin therapy made with antibodies sourced from healthy donors. The label of the intravenously infused therapy carries a black box warning for the risks of thrombosis, renal dysfunction, and acute renal failure. Kedrion expects Qivigy will become available in early 2026.
—The long journey of Stealth BioTherapeutics drug elamipretide has culminated in an accelerated FDA approval, making the drug the first medicine for the ultra-rare mitochondrial disorder Barth syndrome. Stealth will commercialize the once-daily subcutaneously injected drug under the brand name Forzinity.
—The European Commission granted marketing authorization for Biogen’s Zurzuvae as a treatment for postpartum depression. The drug, taken as a daily pill taken for 14 days, was developed by Sage Therapeutics and won FDA approval in 2023. Biogen has rights to the molecule outside of the U.S. except for Japan, Taiwan, and South Korea.
—The European Commission approved Deciphera Pharmaceuticals’ vimseltinib, brand name Romvimza, making it the first and only therapy for tenosynovial giant cell tumor in the European Union. The FDA approved Romvimza this past February. Deciphera operates as a subsidiary of Ono Pharmaceutical, which acquired the biotech for $2.4 billion in 2024.
—Enbumyst, Corstasis Therapeutics’ nasal spray formulation of the diuretic bumetanide, received FDA approval as a treatment for edema associated with congestive heart failure, liver disease, and kidney disease. The approval is based on clinical trial results showing a diuretic response comparable to intravenously administered bumetanide.
—Johnson & Johnson received FDA approval for Inlexzo as a treatment for non-muscle invasive bladder cancer. The drug/device combination product enables extended local delivery of gemcitabine, a chemotherapy.
Expanded FDA Approvals
—Syndax Pharmaceuticals’ Revuforj is now approved for treating adults and children whose relapsed or refractory acute myeloid leukemia carries an NPM1 mutation. Revuforj is an oral small molecule menin inhibitor. The drug was first approved last year as a treatment for advanced leukemia driven by KMT2A mutations.
—Roche drug Gazyva is now approved for treating adults who are receiving standard therapy for active lupus nephritis. Gazyva is an antibody that binds to the CD20 protein on B cells, leading to depletion of these autoimmune disease-driving immune cells. The drug found its first applications as a treatment first certain blood cancers.
—AstraZeneca and Amgen drug Tezspire expanded its approved uses to include treatment of patients age 12 and older who have chronic rhinosinusitis with nasal polyps. It’s the first biologic approved for this indication. Tezspire was first approved in 2021 as a treatment for asthma.
—Regeneron Pharmaceuticals drug Libtayo expanded its FDA approved indications to include use as an adjuvant therapy for cutaneous squamous cell carcinoma. Regeneron said the new FDA decision makes Libtayo the first immunotherapy approved as an adjuvant for this common type of skin cancer. Adjuvants are used after the initial line of treatment to prevent recurrence of cancer.
—Jazz Pharmaceuticals drug Zepzelca expanded its FDA approval to include first-line treatment of extensive-stage small cell lung cancer when used alongside the Roche immunotherapy Tecentriq. Zepzelca, an intravenously infused drug, was first approved in 2020 as a treatment for metastatic small cell lung cancer.
—The label of Johnson & Johnson biologic drug Tremfya now includes treatment of pediatric patients with plaque psoriasis and active psoriatic arthritis. Tremfya is an antibody designed to block IL-23, a signaling protein involved in inflammation. The new approval makes this drug the first IL-23 inhibitor approved for pediatric patients in these indications.
—Vyjuvek, a Krystal Biotech gene therapy for the rare inherited skin disease dystrophic epidermolysis bullosa, may now be used to treat children from birth. The label update for the topical gel also gives patients full flexibility in the application of the product. When Vyjuvek first won FDA approval in 2023, the regulatory decision covered patients age 6 months and older and the product could only be applied by a clinician.
—Incyte’s atopic dermatitis drug Opzelura expanded its FDA approval to include the treatment of children ages 2 to 11. FDA approval of Opzelura in 2021 covered its use in patients age 12 and older.
Complete Response Letters and Other Regulatory Setbacks
—The FDA turned down Xspray Pharma’s application seeking approval of Dasynoc as a treatment for chronic myeloid leukemia and acute lymphoblastic leukemia. According to the company, the FDA cited problems at the drug’s contract manufacturer. While no issues were raised in the Dasynoc production line, the FDA is pausing approvals of products manufactured at this facility until corrective measures are implemented.
—Manufacturing problems were also cited in the complete response letter for Sentynl Therapeutics’ drug for CUTX-101. This drug was developed as a treatment for Menkes disease, a rare disorder caused by mutations to the gene that codes for ATP7A, a copper transporter protein. The FDA letter did not raise any concerns about the Sentynl therapy’s efficacy and safety.
—The FDA turned down Scholar Rock’s application seeking approval of apitegromab as a treatment for spinal muscular atrophy. According to the biotech, the only approvability problem cited was manufacturing issues at the Indiana fill and finish site of contract manufacturer Catalent, which is now owned by Novo Nordisk. This site has scuttled other regulatory submissions. Over the summer, the FDA cited problems at the Indiana site in its rejection letter for a Regeneron Pharmaceuticals drug.
—Partners Otsuka Pharmaceutical and Lundbeck hit a setback in their bid to expand Rexulti to post-traumatic stress disorder when used alongside the antidepressant sertraline. According to the companies, the FDA’s complete response letter said the application lacks sufficient evidence of effectiveness. In July, an FDA advisory committee voted that efficacy had not been established. The companies said they will review the letter with the FDA to determine next steps.
—Saol Therapeutics received a complete response letter for SL1009 as a treatment for pyruvate dehydrogenase complex deficiency, an ultra-rare mitochondrial disease affecting children. The company did not describe the observations cited by the regulator, other than to say they did not involve manufacturing. Saol said it is looking for a path forward that does not require conducting another clinical trial.
—Ocaliva, an Intercept Pharmaceuticals drug that 2016 accelerated FDA approval made it a second-line treatment for the rare liver disease primary biliary cholangitis, has been voluntarily withdrawn from the market. Intercept said the move follows a request from the FDA, which had flagged safety concerns about the product.
Photo: Streeter Lecka, Getty Images
