FDA News Month in Review: November 2024

This is the latest iteration of our monthly recap of news and updates from the US Food and Drug Administration (FDA).

For our November 2024 recap, we spotlight 24 pieces of pipeline news, including 12 regulatory actions and 12 announcements of pipeline updates. Be sure to subscribe for a recap of the therapies, companies, and individuals moving the needle in healthcare during the past month, delivered on the first Saturday of each new month!

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FDA Regulatory Actions

FDA Approves VARIPULSE Platform for Treatment of Atrial Fibrillation

On November 7, 2024, Johnson & Johnson MedTech announced FDA approval of the VARIPULSE pulsed field ablation (PFA) platform for drug-refractory paroxysmal atrial fibrillation. Based on 12-month data from the admIRE trial, the platform demonstrated 100% acute procedural success with a favorable safety profile. Fully integrated with the CARTO 3 System, VARIPULSE offers electrophysiologists precise energy delivery, real-time imaging, and a streamlined workflow for treating atrial fibrillation.

FDA Suggests Removing Oral Phenylephrine as OTC Monograph Nasal Decongestant Ingredient

​​On November 9, 2024, the FDA proposed removing oral phenylephrine as an active ingredient in over-the-counter nasal decongestant products. Based on a review of recent data and unanimous advisory committee findings, the agency concluded that oral phenylephrine is not effective for relieving nasal congestion. The proposal does not affect phenylephrine nasal sprays and allows public comment before issuing a final order.

FDA Issues CRL to Obeticholic Acid (Ocaliva), Denies Full Approval for PBC

On November 12, 2024, the FDA issued a Complete Response Letter (CRL) to Intercept Pharmaceuticals for obeticholic acid (Ocaliva) as a treatment for primary biliary cholangitis (PBC). The CRL follows a negative advisory committee vote questioning the drug’s benefit-risk profile and inability to verify clinical outcome benefits with available data. Ocaliva remains available for appropriate PBC patients under accelerated approval, while new second-line therapies, elafibranor and seladelpar, recently gained FDA approval.

FDA Accepts Resubmission of Pz-cel Gene Therapy BLA for Epidermolysis Bullosa

On November 12, 2024, the FDA accepted Abeona Therapeutics' resubmitted Biologics License Application (BLA) for prademagene zamikeracel (pz-cel), an investigational gene therapy for recessive dystrophic epidermolysis bullosa (RDEB), setting a target action date of April 29, 2025. Pz-cel utilizes genetically modified patient-derived skin cells to deliver a functional COL7A1 gene, enabling collagen VII production to heal chronic wounds associated with RDEB. If approved, pz-cel would be the second gene therapy for RDEB, following beremagene geperpavec's (B-VEC) 2023 approval, and has received multiple FDA designations, including Orphan Drug and Breakthrough Therapy.

FDA Approves Minocycline Hydrochloride Extended Release Capsules for Individuals with Rosacea

On November 15, 2024, Journey Medical Corporation announced the FDA approval of minocycline hydrochloride modified release capsules 40 mg (Emrosi) for inflammatory lesions and erythema in adults with rosacea. Based on successful Phase 3 trials (MVOR-1 and MVOR-2), the treatment demonstrated superior efficacy in reducing lesion count and erythema compared to placebo and doxycycline, with no serious safety concerns. Emrosi offers a novel oral option for managing this chronic inflammatory skin condition affecting millions in the U.S.

FDA Accepts Resubmitted sBLA for Dupilumab Treatment of Chronic Spontaneous Urticaria

On November 15, 2024, Regeneron Pharmaceuticals and Sanofi's resubmitted supplemental Biologics License Application (sBLA) for dupilumab (Dupixent) was accepted by the FDA for the treatment of chronic spontaneous urticaria (CSU) in adults and adolescents aged ≥12 years. The sBLA is supported by the positive results from the LIBERTY-CUPID phase 3 program, showing significant reductions in itch and hives in patients with CSU inadequately managed by antihistamines. Dupilumab, a monoclonal antibody targeting IL-4 and IL-13 pathways, is already approved for other conditions and is expected to receive an FDA decision by April 18, 2025.

FDA Issues CRL to Avacincaptad Pegol sNDA for Geographic Atrophy

On November 15, 2024, the FDA issued a Complete Response Letter (CRL) for the supplemental New Drug Application (sNDA) of avacincaptad pegol (IZERVAY) for treating geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Astellas Pharma had sought to update the US prescribing information with positive 2-year data from the GATHER2 Phase 3 trial, but the FDA raised a statistical concern regarding labeling language, without addressing the treatment's safety or benefit-risk profile. While expressing disappointment, Astellas remained committed to resolving the issue with the FDA.

Gildeuretinol for Stargardt Secures FDA Rare Pediatric, Fast Track Status

On November 18, 2024, Alkeus Pharmaceuticals announced Gildeuretinol (ALK-001), an investigational oral therapy for Stargardt disease, received Rare Pediatric Disease and Fast Track designations from the US FDA. These designations complement previous Breakthrough Therapy and Orphan Drug designations. Data from the TEASE-1 trial showed that gildeuretinol significantly slowed lesion growth in late-stage Stargardt disease, while interim results from the TEASE-3 trial indicated stability in visual acuity for early-stage patients.

FDA Approves Bimekizumab for Adults with Hidradenitis Suppurativa

On November 20, 2024, the FDA approved UCB’s bimekizumab-bkzx (Bimzelx) for the treatment of moderate-to-severe hidradenitis suppurativa (HS) in adult patients. Bimekizumab, a monoclonal antibody that targets both IL-17A and IL-17F cytokines, was shown in Phase 3 trials to significantly reduce HS symptoms, with sustained improvements up to 48 weeks. The approval was based on the results of the BE HEARD I and BE HEARD II studies, which demonstrated a marked reduction in abscesses, nodules, and pain, with a safety profile consistent with previous trials across other indications.

FDA Accepts BLA for Denosumab Biosimilar

On November 20, 2024, Organon and Shanghai Henlius Biotech announced FDA acceptance of their biologics license application for HLX14, a denosumab biosimilar. Based on data from analytical studies and clinical trials, including a phase 3 study in postmenopausal women with osteoporosis, HLX14 demonstrated efficacy, safety, and pharmacokinetic similarity to PROLIA. If approved, HLX14 will expand biosimilar options for managing osteoporosis and other conditions treated with denosumab.

FDA Approves Acoramidis (Attruby) for ATTR-CM

On November 22, 2024, BridgeBio Pharma announced Acoramidis (Atwas truby) approved by the US FDA for treating adults with transthyretin amyloid cardiomyopathy (ATTR-CM) to reduce cardiovascular death and related hospitalizations. This oral medication is the first to provide near-complete stabilization of transthyretin (TTR). The approval is based on the Phase 3 ATTRibute-CM trial, which demonstrated a 42% reduction in all-cause mortality and cardiovascular-related hospitalizations.

FDA Accepts Alnylam’s sNDA for Vutrisiran for ATTR-CM

On November 25, 2024, Alnylam Pharmaceuticals' supplemental New Drug Application (sNDA) for vutrisiran, aimed at treating transthyretin amyloidosis with cardiomyopathy (ATTR-CM), has been accepted by the US FDA, with a target PDUFA date of March 23, 2025. The application is supported by positive results from the Phase 3 HELIOS-B trial, which showed significant reductions in all-cause mortality and recurrent cardiovascular events, as well as improvements in functional capacity and quality of life. If approved, vutrisiran could become the first therapeutic to address both polyneuropathy and cardiomyopathy in ATTR amyloidosis.

Pipeline Updates

ESSENCE: Semaglutide Improves Fibrosis, Resolves Steatohepatitis in MASH

Announced on November 1, 2024, Novo Nordisk’s Phase 3 ESSENCE trial has shown that once-weekly subcutaneous semaglutide 2.4 mg significantly improves liver fibrosis and resolves steatohepatitis in adults with metabolic dysfunction-associated steatohepatitis (MASH) and moderate to advanced liver fibrosis. At 72 weeks, 37% of patients on semaglutide showed improvement in liver fibrosis with no worsening of steatohepatitis, compared to 22.5% on placebo. The drug also demonstrated a high rate of steatohepatitis resolution (62.9% vs. 34.1% placebo), with a safety profile consistent with prior trials.

Phase 3 Data Shows Lumateperone Delays Schizophrenia Relapse Longer Than Placebo

On November 5, 2024, Intra-Cellular Therapies announced positive Phase 3 results for lumateperone (CAPLYTA) 42 mg in preventing relapse in schizophrenia patients. In the Study 304 trial, lumateperone significantly delayed the time to relapse compared to placebo, with a 63% reduction in relapse risk (hazard ratio 0.37; P = .0002). The drug was generally well-tolerated, with common side effects including headaches, somnolence, and dizziness, supporting its long-term use for maintaining symptom control in schizophrenia.

Idorsia Launches Aprocitentan (TRYVIO) in US For Treatment of Hypertension

On November 15, 2024, Idorsia Pharmaceuticals announced the availability of aprocitentan (TRYVIO™) in the US for treating hypertension in adults with inadequately controlled blood pressure, particularly when combined with other antihypertensive drugs. The approval was based on positive results from the Phase 3 PRECISION trial, which demonstrated significant reductions in systolic blood pressure with aprocitentan 12.5 mg and 25 mg compared to placebo. Aprocitentan, the first FDA-approved treatment targeting the endothelin system for hypertension, offers a novel therapeutic option, especially for patients with treatment-resistant hypertension.

Seladelpar (Livdelzi) Demonstrates Long-Term Benefit for Primary Biliary Cholangitis

On November 15, 2024, Gilead announced seladelpar (Livdelzi) showed significant long-term benefits for patients with primary biliary cholangitis (PBC) in pooled interim data from the Phase 3 ASSURE study. By month 30, 81% of patients achieved a sustained composite biochemical response, and 41% achieved normalization of alkaline phosphatase (ALP) levels, with no new safety concerns identified. Seladelpar’s ability to reduce ALP levels, a key marker of liver health in PBC, offers a promising treatment option, especially for those not responding to first-line therapies.

Interim Phase 1 Update Shows Favorable Effect of Nex-z for ATTR-CM

On November 16, 2024, Intellia announced interim 12-month data from the Phase 1 trial of nexiguran ziclumeran (nex-z), an investigational CRISPR-Cas9 gene editing therapy for transthyretin amyloidosis with cardiomyopathy (ATTR-CM), demonstrated rapid and sustained reductions in serum TTR levels, with a 90% mean reduction by month 12. Despite some transient infusion-related reactions, the treatment was well tolerated, and improvements in cardiac markers, such as NT-proBNP and troponin T, were observed. These findings suggest that nex-z may provide a promising therapeutic approach to slowing disease progression in ATTR-CM.

SUMMIT Trial Proves Tirzepatide's Benefit in HFpEF with Obesity

On November 16, 2024, Eli Lilly and Company announced that tirzepatide significantly reduced the risk of worsening heart failure or cardiovascular death by 38% in patients with heart failure with preserved ejection fraction (HFpEF) and obesity in the Phase 3 SUMMIT trial. The trial also showed a 12-21% reduction in body weight and a significant improvement in health status and exercise tolerance. These results suggest that tirzepatide could be a breakthrough treatment for obesity-related HFpEF, with Eli Lilly submitting the drug for FDA approval.

Zerlasiran 60-Week Data Reinforce Lp(a) Reductions Observed in ALPACAR-360

On November 18, 2024, Silence Therapeutics announced the ALPACAR-360 trial demonstrated that zerlasiran provided durable and significant reductions in lipoprotein(a) [Lp(a)] for at least 60 weeks, with a mean reduction of up to 96% from baseline. Zerlasiran was well-tolerated, with the most common adverse effects being mild injection site reactions. These findings support the potential of zerlasiran as a long-term treatment for patients with elevated Lp(a), a key genetic risk factor for atherosclerotic cardiovascular disease (ASCVD).

LUNA, OPTIC Data Support Long-Term Benefit of Ixo-Vec for Wet AMD

On November 18, 2024, Adverum Biotechnologies announced topline results from the LUNA Phase 2 trial and a 4-year follow-up of the OPTIC trial, showing the long-term efficacy and safety of intravitreal ixoberogene soroparvovec (Ixo-vec) gene therapy for neovascular (wet) AMD (nAMD). In the LUNA trial, the 6E10 dose of Ixo-vec resulted in a significant reduction in treatment burden (≥80%) and injection-free patients (≥50%), with minimal inflammation. The 4-year OPTIC study also showed sustained efficacy, with an 86% reduction in annualized anti-VEGF injections and nearly 50% of patients remaining injection-free. Adverum plans to initiate Phase 3 trials in 2025.

Positive Phase 3 Results Announced for JNJ-2113 Treatment of Psoriasis

On November 19, 2024, Protagonist Therapeutics announced positive results from the phase 3 ICONIC-LEAD and ICONIC-TOTAL studies evaluating the oral peptide JNJ-2113 (icotrokinra) for moderate-to-severe psoriasis. In these trials, JNJ-2113 showed significant improvements in skin clearance, with up to 74.1% of participants achieving an Investigator's Global Assessment (IGA) score of 0/1 by 24 weeks, and 64.9% achieving a PASI 90. The safety profile was comparable to placebo, with similar rates of adverse events, and further studies for psoriatic arthritis and ulcerative colitis are planned for 2025.

J&J Submits sBLA for Guselkumab (Tremfya) Subcutaneous Induction Regimen in UC

On November 22, 2024, Johnson & Johnson submitted a supplemental Biologics License Application (sBLA) for a subcutaneous induction regimen of guselkumab (Tremfya) to treat adults with moderately to severely active ulcerative colitis (UC). The submission is based on data from the Phase 3 ASTRO study, which demonstrated that guselkumab at 400 mg administered at weeks 0, 4, and 8 significantly improved clinical remission, endoscopic, and histologic endpoints. If approved, this regimen would provide patients with a fully subcutaneous induction and maintenance treatment option for UC.

Obesity Drug MariTide Achieves Up to 20% Weight Loss in Phase 2 Trial

On November 26, 2024, Amgen's 52-week Phase 2 trial of maridebart cafraglutide (MariTide), an investigational antibody peptide conjugate, demonstrated up to ~20% average weight loss in individuals with obesity or overweight, with no weight loss plateau. The treatment also resulted in significant improvements in cardiometabolic parameters, including reductions in HbA1C, blood pressure, and triglyceride levels. Safety data showed gastrointestinal issues, such as nausea and constipation, as the most common adverse events, which were reduced with dose escalation. Further trials are planned to evaluate long-term effects and dosing strategies.

ONS-5010 for Wet AMD Fails to Meet Noninferiority in NORSE EIGHT Trial

On November 27, 2024, Outlook Therapeutics announced preliminary results from the NORSE EIGHT trial, revealing that ONS-5010 (LYTENAVA), an ophthalmic formulation of bevacizumab, did not meet the pre-specified non-inferiority endpoint compared to ranibizumab for treating nAMD. The trial showed a mean change in best-corrected visual acuity (BCVA) of +4.2 letters with ONS-5010 versus +6.3 letters with ranibizumab (P = .0863), missing the non-inferiority margin. Outlook Therapeutics still plans to resubmit the Biologics License Application (BLA) in early 2025.