The FDA has halted clinical testing of an Intellia Therapeutics gene-editing remedy following a report {that a} affected person in a Part 3 research was hospitalized with liver problems.
Intellia stated the liver issues met the trial protocol’s standards for pausing the studies, which the corporate did on Monday. The remedy, nexiguran ziclumeran, or nex-z, is an experimental therapy for the uncommon illness transthyretin amyloidosis (ATTR). In response to Intellia, the injured affected person acquired nex-z on Sept. 30. On Oct. 24, this affected person developed excessive ranges of liver enzymes and compounds indicative of injury to the organ. Intellia stated the FDA on Wednesday verbally notified the corporate that the 2 Part 3 checks of the experimental remedy at the moment are underneath a medical maintain.
In ATTR, misfolded variations of the liver protein transthyretin (TTR) result in accumulation of amyloid protein in tissues, inflicting issues within the physique. Nex-z makes use of the CRISPR gene-editing know-how to inactivate the gene that codes for TTR protein. Nex-z had superior to 2 Part 3 checks, one for ATTR cardiomyopathy and the opposite for ATTR polyneuropathy. The affected person who developed liver problems was within the cardiomyopathy research.
New ATTR medication are gaining traction available in the market. Whereas Pfizer medication Vyndaqel and Vyndamax are established as commonplace ATTR cardiomyopathy therapies, FDA approvals in the past year for BridgeBio Pharma’s Attruby and Alnylam Pharmaceuticals’ Amvuttra carry sufferers further choices. Amvuttra was first permitted for ATTR polyneuropathy in 2022.
The ATTR medication at the moment obtainable are continual therapies. Intellia’s nex-z affords the potential for a one-time therapy. The corporate is growing nex-z underneath a partnership with Regeneron Prescription drugs. Intellia leads medical improvement of nex-z whereas Regeneron holds an choice to co-commercialize the remedy within the U.S.
The FDA advised Intellia a proper medical maintain letter for nex-z’s Part 3 research can be issued inside 30 days. Within the meantime, the corporate stated it intends to work with the company “to handle the medical maintain as expeditiously as doable.”
Right here’s a recap of different current regulatory developments:
FDA and EU Regulatory Approvals
—GSK a number of myeloma drug Blenrep is returning to the market. Three years in the past, the pharma big withdrew the antibody drug conjugate after it failed its confirmatory research as a monotherapy. GSK’s resubmission is predicated on Part 3 checks of the drug together with commonplace therapies and as an earlier line of therapy. Whereas these research had been profitable, 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 remedy.
—The FDA approved Bayer’s Lynkuet as a therapy for moderate-to-severe vasomotor signs of menopause. The oral small molecule inhibits the NK1 and NK3 receptors, each of which regulate physique temperature. Lynkuet will compete in opposition to 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 continual and in the end deadly lung dysfunction. The twice-daily tablet affords a distinct mechanism of motion than Ofev, an older Boehringer IPF drug that’s a blockbuster vendor.
—Rhapsido, a BTK inhibitor found and developed by Novartis, landed FDA approval for treating chronic spontaneous urticaria, an inflammatory pores and skin dysfunction that results in continual hives. The regulatory resolution covers use of the twice-daily tablet by sufferers whose illness doesn’t reply to therapy with first-line therapy with antihistamines.
—The FDA permitted Crinetics’s Palsonify as a first-line treatment for acromegaly, a uncommon endocrine dysfunction. The once-daily tablet affords an oral various to blockbuster medication from Novartis and Ipsen which can be administered as injections.
—The FDA approved Keytruda Qlex, an injectable model of the Merck immunotherapy Keytruda. The regulatory resolution covers practically all the most cancers indications lined by the unique intravenously infused product. Keytruda Qlex is run as a subcutaneous injection that takes two minutes or much less in comparison with the half hour required for a Keytruda infusion.
—Kedrion Biopharma landed FDA approval for Qivigy for the therapy of adults with major humoral immunodeficiency, a bunch of problems that compromise immune system operate. The drug is an intravenous immunoglobulin remedy made with antibodies sourced from wholesome donors. The label of the intravenously infused remedy carries a black field warning for the dangers of thrombosis, renal dysfunction, and acute renal failure. Kedrion expects Qivigy will turn out to be obtainable in early 2026.
—The long journey of Stealth BioTherapeutics drug elamipretide has culminated in an accelerated FDA approval, making the drug the primary drugs for the ultra-rare mitochondrial dysfunction Barth syndrome. Stealth will commercialize the once-daily subcutaneously injected drug underneath the model title Forzinity.
—The European Fee granted marketing authorization for Biogen’s Zurzuvae as a therapy for postpartum despair. The drug, taken as a every day tablet taken for 14 days, was developed by Sage Therapeutics and won FDA approval in 2023. Biogen has rights to the molecule exterior of the U.S. aside from Japan, Taiwan, and South Korea.
—The European Fee approved Deciphera Pharmaceuticals’ vimseltinib, model title Romvimza, making it the primary and solely remedy for tenosynovial big cell tumor within 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, acquired FDA approval as a treatment for edema related to congestive coronary heart failure, liver illness, and kidney illness. The approval is predicated on medical trial outcomes exhibiting a diuretic response corresponding to intravenously administered bumetanide.
—Johnson & Johnson acquired FDA approval for Inlexzo as a treatment for non-muscle invasive bladder cancer. The drug/system mixture product permits prolonged native supply of gemcitabine, a chemotherapy.
Expanded FDA Approvals
—Syndax Prescription drugs’ Revuforj is now permitted for treating adults and youngsters 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 permitted for treating adults who’re receiving commonplace remedy for active lupus nephritis. Gazyva is an antibody that binds to the CD20 protein on B cells, resulting in depletion of those autoimmune disease-driving immune cells. The drug discovered its first functions as a therapy first sure blood cancers.
—AstraZeneca and Amgen drug Tezspire expanded its approved uses to incorporate therapy of sufferers age 12 and older who’ve continual rhinosinusitis with nasal polyps. It’s the primary biologic permitted for this indication. Tezspire was first approved in 2021 as a therapy for bronchial asthma.
—Regeneron Prescription drugs drug Libtayo expanded its FDA permitted indications to incorporate use as an adjuvant therapy for cutaneous squamous cell carcinoma. Regeneron stated the brand new FDA resolution makes Libtayo the primary immunotherapy permitted as an adjuvant for this frequent sort of pores and skin most cancers. Adjuvants are used after the preliminary line of therapy to forestall recurrence of most cancers.
—Jazz Prescription drugs drug Zepzelca expanded its FDA approval to incorporate first-line therapy of extensive-stage small cell lung most cancers when used alongside the Roche immunotherapy Tecentriq. Zepzelca, an intravenously infused drug, was first permitted in 2020 as a therapy for metastatic small cell lung most cancers.
—The label of Johnson & Johnson biologic drug Tremfya now contains treatment of pediatric patients with plaque psoriasis and lively psoriatic arthritis. Tremfya is an antibody designed to dam IL-23, a signaling protein concerned in irritation. The brand new approval makes this drug the primary IL-23 inhibitor permitted for pediatric sufferers in these indications.
—Vyjuvek, a Krystal Biotech gene remedy for the uncommon inherited pores and skin illness dystrophic epidermolysis bullosa, could now be used to deal with kids from delivery. The label update for the topical gel additionally offers sufferers full flexibility within the software of the product. When Vyjuvek first won FDA approval in 2023, the regulatory resolution lined sufferers age 6 months and older and the product may solely be utilized by a clinician.
—Incyte’s atopic dermatitis drug Opzelura expanded its FDA approval to incorporate the therapy of youngsters ages 2 to 11. FDA approval of Opzelura in 2021 lined its use in sufferers age 12 and older.
Full Response Letters and Different Regulatory Setbacks
—The FDA turned down Xspray Pharma’s software in search of approval of Dasynoc as a therapy for continual myeloid leukemia and acute lymphoblastic leukemia. In response to the corporate, the FDA cited issues on the drug’s contract producer. Whereas no points had been raised within the Dasynoc manufacturing line, the FDA is pausing approvals of merchandise manufactured at this facility till corrective measures are carried out.
—Manufacturing problems had been additionally cited within the full response letter for Sentynl Therapeutics’ drug for CUTX-101. This drug was developed as a therapy for Menkes illness, a uncommon dysfunction attributable to mutations to the gene that codes for ATP7A, a copper transporter protein. The FDA letter didn’t increase any issues concerning the Sentynl remedy’s efficacy and security.
—The FDA turned down Scholar Rock’s software in search of approval of apitegromab as a therapy for spinal muscular atrophy. In response to the biotech, the one approvability downside cited was manufacturing points on the Indiana fill and end web site of contract producer Catalent, which is now owned by Novo Nordisk. This web site has scuttled different regulatory submissions. Over the summer season, the FDA cited problems at the Indiana site in its rejection letter for a Regeneron Prescription drugs drug.
—Companions Otsuka Pharmaceutical and Lundbeck hit a setback of their bid to develop Rexulti to post-traumatic stress dysfunction when used alongside the antidepressant sertraline. In response to the businesses, the FDA’s full response letter stated the appliance lacks sufficient evidence of effectiveness. In July, an FDA advisory committee voted that efficacy had not been established. The businesses stated they are going to evaluation the letter with the FDA to find out subsequent steps.
—Saol Therapeutics acquired a complete response letter for SL1009 as a therapy for pyruvate dehydrogenase advanced deficiency, an ultra-rare mitochondrial illness affecting kids. The corporate didn’t describe the observations cited by the regulator, apart from to say they didn’t contain manufacturing. Saol stated it’s searching for a path ahead that doesn’t require conducting one other medical trial.
—Ocaliva, an Intercept Prescription drugs drug that 2016 accelerated FDA approval made it a second-line therapy for the uncommon liver illness major biliary cholangitis, has been voluntarily withdrawn from the market. Intercept stated the transfer follows a request from the FDA, which had flagged security issues concerning the product.
Photograph: Streeter Lecka, Getty Pictures
