Catch up on any of the neurology news headlines you may have missed over the course of October 2023, compiled all into one place by the NeurologyLive® team.
The FDA was busy in October 2023, making a number of decisions on potential new therapeutic agents including granting approvals, issuing a complete response letter, granting an allowance, and lifting a clinical trial hold, among other actions.
With all the treatments that have progressed through the pipeline of clinical development, the NeurologyLive® team has been hard at work covering all the agency movements to make sure you are up to date on the latest news in neurology. To give you a chance to catch up on any of the headlines you may have missed over the course of the last month, we’ve compiled all the updates into one place. The coverage includes the latest FDA approvals, new designations, submissions and resubmissions, and clinical trial initiations and holds.
Click the read more buttons for more details and information about each update.
Earlier in the month, on October 9, the FDA issued a complete response letter (CRL) to Alnylam Pharmaceuticals for patisiran (Onpattro), an RNAi therapeutic, for the treatment of patients with cardiomyopathy of transthyretin-mediated (ATTR) amyloidosis. Patisiran, an intravenously administered therapy, has already been approved as a treatment for polyneuropathy of hereditary ATTR amyloidosis in adults.1
In its release, the FDA noted that the clinical meaningfulness of patisiran’s treatment effects for the cardiomyopathy of ATTR amyloidosis was not confirmed. Thus in its present form, the company’s supplemental new drug application (sNDA) for the therapy could not be approved. No issues with clinical safety, study conduct, drug quality or manufacturing were indicated in the CRL. As a result, the company plans to no longer pursue an expanded indication for patisiran in the United States.
“First and foremost, our hearts go out to patients with the cardiomyopathy of ATTR amyloidosis who are living with a rapidly progressive, debilitating and fatal disease and face significant unmet need. While we are disappointed by this decision, we are committed to supporting them and are well positioned to address their needs with continued innovation that can potentially help improve their outcomes and treatment experience,” Yvonne Greenstreet, MBChB, chief executive officer at Alnylam Pharmaceuticals, said in a statement.1
A few days later, on October 12, the FDA lifted a clinical hold on PepGen's investigational new drug application (IND) for its phase 1 study assessing PGN-EDODM1, an investigational antisense oligonucleotide (ASO), in patients with myotonic dystrophy type 1 (DM1). The company expects to obtain proof-of-concept data, including transcript splicing and clinical outcome measures, as well as safety data, for treated patients in the study in 2024.2
Originally started in Canada, FREEDOM-DM1 is a randomized, double-blind, placebo-controlled, single-ascending dose study assessing the safety and tolerability of the ASO in 3 cohorts of 5 mg/kg, 10 mg/kg, and 20 mg/kg dose levels. The study also will look at correction of mis-splicing of transcripts and other clinical functional outcome measures throughout.
"We have worked closely with the FDA to resolve their questions expeditiously and are pleased that the clinical hold on our DM1 program in the United States has been lifted,” James McArthur, PhD, president and chief executive officer, PepGen, said in a statement.2 "Our novel PGN-EDODM1 approach targets the toxic RNA species responsible for the disease, and the strength of our Enhanced Delivery Oligonucleotide (EDO) safety preclinical package has enabled us to launch this study in both the U.S. and internationally at doses that we believe could provide a clinically meaningful benefit to patients."
A couple of days later, on October 17, the FDA approved UCB Pharma’s investigational agent zilucoplan, a complement C5 inhibitor, to treat patients with myasthenia gravis (MG). Approved under the market name Zilbrysq, the subcutaneously delivered medication is indicated for those with acetylcholine receptor antibody positive (AChR-Ab+) generalized MG, further expanding the toolbox of options for patients with the disease.3
Data from the large-scale, double-blind, placebo-controlled, phase 3 RAISE study (NCT04115293) was the basis for the approval, in which zilucoplan demonstrated rapid and clinically meaningful improvements in MG-specific efficacy outcomes. After 12 weeks of treatment, zilucoplan met its primary end point, showing a placebo-corrected mean improvement of 2.09 points on Myasthenia Gravis Activities of Daily Living (MG-ADL) score.4
"For people with gMG, the unpredictable nature of the severity and frequency of symptoms can be debilitating and can have a substantial impact on many aspects of their day-to-day lives. In addition to muscle weakness, people living with gMG experience fatigue, affecting their overall quality of life,” lead investigator James F. Howard, MD, Distinguished Professor of Neuromuscular Disease and professor of neurology at The University of North Carolina at Chapel Hill School of Medicine, said in a statement.3 "Zilucoplan demonstrated rapid improvements in gMG symptoms at Week 12, with differences seen as early as one week, and provides a new treatment option for a broad population of AChR antibody-positive gMG patients. Zilucoplan is designed for continued daily use."
One day later, on October 18, the FDA allowed Tiziana Life Sciences’ agent foralumab, a fully human intranasal anti-CD3 monoclonal antibody, to be taken at home and self-administered for the treatment of patients living with multiple sclerosis (MS). The company noted that this decision by the FDA to allow patients to self-administer this therapy at home is a significant advancement in the landscape of care in MS, increasing accessibility and allowing for more convenience for patients with this condition.5
Foralumab is designed to bind to T cell receptor and dampens inflammation by modulating T cell function, thereby suppressing effector features in multiple immune cell subsets. The agent is administered intranasally, providing a novel avenue for the treatment of inflammatory human diseases. Tiziana also noted they developed delivery device training materials and refined them in collaboration with the agency. Therefore, patients with MS will be trained in the use of the nasal device in accordance with the instructed materials.
“Traditionally, patients with MS had to visit healthcare facilities for treatment, which could be inconvenient and burdensome. The FDA's approval for home dosing of foralumab will transform the way patients manage their condition, offering them greater control over their treatment schedules and the convenience of receiving care in their familiar environment,” Gabriele Cerrone, executive chairman and interim chief executive officer at Tiziana Life Sciences, said in a statement.5 "We are elated with the FDA's allowance for home dosing of intranasal foralumab. This step significantly aligns with our mission to make innovative therapies more accessible to patients and ultimately improve their quality of life. We believe that this treatment approach will revolutionize the way patients with MS manage their condition."
About a week later, on October 26, the FDA approved Santhera Pharmaceuticals' investigational agent vamorolone (now marketed as Agamree) oral suspension 40 mg/mL for the treatment of patients with Duchenne muscular dystrophy (DMD) aged 2 years and older. The therapy is a first-in-class dissociative steroid, that aims to retain the anti-inflammatory activity of corticosteroids while decreasing the deleterious adverse events (AEs).6
Data from phase 2b data from the VISION-DMD study (NCT03439670) was the basis for the approval, in which the agent met its primary end point of superiority of change in time to stand test (TTSTAND) velocity relative to placebo. The primary end point, superiority in change of TTSTAND velocity, was represented by a difference of 0.06 (95% CI, 0.02-0.10) rises per second from baseline in the treated group (P = .002).
"This approval introduces a novel and alternative treatment choice for individuals dealing with DMD. Its distinctive structure and mechanism of action leads to tolerable side effects with matching efficacy to traditional corticosteroid treatment options and offers an excellent alternate treatment option," Stanley Iyadurai, MD, PhD, senior vice president of medical affairs and drug discovery at Catalyst Pharmaceuticals, told NeurologyLive®. "This treatment represents a valuable addition to the range of tools available for managing patients with DMD. It can serve as a fundamental treatment option that can be added on to existing therapies, including exon-skipping therapies and dystrophin restoration therapies."