The FDA has halted scientific testing of an Intellia Therapeutics gene-editing remedy following a report {that a} affected person in a Section 3 research was hospitalized with liver problems.
Intellia stated the liver issues met the trial protocol’s standards for pausing the research, which the corporate did on Monday. The remedy, nexiguran ziclumeran, or nex-z, is an experimental therapy for the uncommon illness transthyretin amyloidosis (ATTR). Based on Intellia, the injured affected person obtained nex-z on Sept. 30. On Oct. 24, this affected person developed excessive ranges of liver enzymes and compounds indicative of harm to the organ. Intellia stated the FDA on Wednesday verbally notified the corporate that the 2 Section 3 assessments of the experimental remedy at the moment are below a scientific 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 Section 3 assessments, 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 out there. Whereas Pfizer medication Vyndaqel and Vyndamax are established as normal ATTR cardiomyopathy therapies, FDA approvals prior to now yr for BridgeBio Pharma’s Attruby and Alnylam Prescription drugs’ Amvuttra convey sufferers further choices. Amvuttra was first authorized for ATTR polyneuropathy in 2022.
The ATTR medication at present out there are persistent therapies. Intellia’s nex-z gives the potential for a one-time therapy. The corporate is creating nex-z below a partnership with Regeneron Prescription drugs. Intellia leads scientific growth of nex-z whereas Regeneron holds an choice to co-commercialize the remedy within the U.S.
The FDA informed Intellia a proper scientific maintain letter for nex-z’s Section 3 research could be issued inside 30 days. Within the meantime, the corporate stated it intends to work with the company “to deal with the scientific maintain as expeditiously as potential.”
Right here’s a recap of different latest 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 large withdrew the antibody drug conjugate after it failed its confirmatory research as a monotherapy. GSK’s resubmission relies on Section 3 assessments of the drug together with normal therapies and as an earlier line of therapy. Whereas these research have been profitable, the FDA authorized Blenrep as a third-line or later a number of myeloma therapy. The drug’s European approval permits its use as a second-line remedy.
—The FDA authorized 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 obtained FDA approval for treating adults with idiopathic pulmonary fibrosis, a persistent and finally deadly lung dysfunction. The twice-daily capsule gives a special 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 persistent spontaneous urticaria, an inflammatory pores and skin dysfunction that results in persistent hives. The regulatory choice covers use of the twice-daily capsule by sufferers whose illness doesn’t reply to therapy with first-line therapy with antihistamines.
—The FDA authorized Crinetics’s Palsonify as a first-line therapy for acromegaly, a uncommon endocrine dysfunction. The once-daily capsule gives an oral different to blockbuster medication from Novartis and Ipsen which are administered as injections.
—The FDA authorized Keytruda Qlex, an injectable model of the Merck immunotherapy Keytruda. The regulatory choice 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 gaggle of issues that compromise immune system perform. 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 develop into out there in early 2026.
—The lengthy 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 below the model identify Forzinity.
—The European Fee granted advertising and marketing authorization for Biogen’s Zurzuvae as a therapy for postpartum melancholy. The drug, taken as a each day capsule taken for 14 days, was developed by Sage Therapeutics and received FDA approval in 2023. Biogen has rights to the molecule outdoors of the U.S. apart from Japan, Taiwan, and South Korea.
—The European Fee authorized Deciphera Prescription drugs’ vimseltinib, model identify Romvimza, making it the primary and solely remedy for tenosynovial large cell tumor within the European Union. The FDA authorized Romvimza this previous 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, obtained FDA approval as a therapy for edema related to congestive coronary heart failure, liver illness, and kidney illness. The approval relies on scientific trial outcomes exhibiting a diuretic response similar to intravenously administered bumetanide.
—Johnson & Johnson obtained FDA approval for Inlexzo as a therapy for non-muscle invasive bladder most cancers. The drug/system mixture product permits prolonged native supply of gemcitabine, a chemotherapy.
Expanded FDA Approvals
—Syndax Prescription drugs’ Revuforj is now authorized 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 authorized final yr as a therapy for superior leukemia pushed by KMT2A mutations.
—Roche drug Gazyva is now authorized for treating adults who’re receiving normal remedy for energetic 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 authorized makes use of to incorporate therapy of sufferers age 12 and older who’ve persistent rhinosinusitis with nasal polyps. It’s the primary biologic authorized for this indication. Tezspire was first authorized in 2021 as a therapy for bronchial asthma.
—Regeneron Prescription drugs drug Libtayo expanded its FDA authorized indications to incorporate use as an adjuvant remedy for cutaneous squamous cell carcinoma. Regeneron stated the brand new FDA choice makes Libtayo the primary immunotherapy authorized as an adjuvant for this widespread kind 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 authorized in 2020 as a therapy for metastatic small cell lung most cancers.
—The label of Johnson & Johnson biologic drug Tremfya now consists of therapy of pediatric sufferers with plaque psoriasis and energetic 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 authorized for pediatric sufferers in these indications.
—Vyjuvek, a Krystal Biotech gene remedy for the uncommon inherited pores and skin illness dystrophic epidermolysis bullosa, might now be used to deal with kids from start. The label replace for the topical gel additionally provides sufferers full flexibility within the utility of the product. When Vyjuvek first received FDA approval in 2023, the regulatory choice 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 utility searching for approval of Dasynoc as a therapy for persistent myeloid leukemia and acute lymphoblastic leukemia. Based on the corporate, the FDA cited issues on the drug’s contract producer. Whereas no points have 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 issues have 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 utility searching for approval of apitegromab as a therapy for spinal muscular atrophy. Based on the biotech, the one approvability drawback cited was manufacturing points on the Indiana fill and end website of contract producer Catalent, which is now owned by Novo Nordisk. This website has scuttled different regulatory submissions. Over the summer time, the FDA cited issues on the Indiana website in its rejection letter for a Regeneron Prescription drugs drug.
—Companions Otsuka Pharmaceutical and Lundbeck hit a setback of their bid to increase Rexulti to post-traumatic stress dysfunction when used alongside the antidepressant sertraline. Based on the businesses, the FDA’s full response letter stated the applying lacks adequate proof of effectiveness. In July, an FDA advisory committee voted that efficacy had not been established. The businesses stated they may assessment the letter with the FDA to find out subsequent steps.
—Saol Therapeutics obtained a full 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, aside from to say they didn’t contain manufacturing. Saol stated it’s searching for a path ahead that doesn’t require conducting one other scientific 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.
Picture: Streeter Lecka, Getty Photos
