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FDA Action Update, July 2024: Approvals, Designations, and Clearances
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Catch up on any of the neurology news headlines you may have missed over the course of July 2024, compiled all into one place by the NeurologyLive® team.
The FDA was busy in July 2024, making a number of decisions on potential new therapeutic agents including granting approvals, designations, and clearances.
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.
FDA Approves Eli Lilly's Donanemab for Early Symptomatic Alzheimer Disease
Early in the month, on July 2, the FDA approved Eli Lilly and Company's donanemab, a 350 mg/20 mL once-monthly injection for IV infusion, for the treatment of adults with early symptomatic Alzheimer disease (AD). Marketed as Kisunla, donanemab is available to patients with mild cognitive impairment (MCI) as well as those with the mild dementia stage of AD, with confirmed amyloid pathology.1
Considered the third approved antiamyloid therapy, donanemab is the first and only medication with evidence to support stopping treatment when amyloid plaques are removed, which can result in lower therapy costs and fewer infusions. Following the removal of aducanumab (Aduhelm; Biogen) from market earlier this year, the class of antiamyloid therapies available for patients with early-stage AD now entails donanemab and lecanemab (Leqembi; Eisai).
"I agree with the FDA decision today regarding approval - the efficacy and safety of donanemab for individuals with MCI or mild dementia because of AD is proven. Results are similar to those obtained with another recently-approved anti-amyloid monoclonal antibody - lecanemab," R. Scott Turner, PhD, MD, FANA, FAAN, the director of the Memory Disorders Program at Georgetown University, told NeurologyLive®. "We now await a decision regarding coverage of donanemab by Medicare (CMS) and other third-party payers. Assuming this follows in the near future, clinicians and eligible patients will have a choice of possible treatments - with lecanemab or donanemab."
Lomecel-B Becomes First Agent to Gain Regenerative Medicine Advanced Therapy Designation for Alzheimer Disease
About a week later, on July 10, the FDA granted regenerative medicine advanced therapy (RMAT) designation to Longeveron’s allogeneic cellular investigational therapy Lomecel-B. With the decision, it became the first such agent to receive RMAT designation for the treatment of AD.2 Lomecel-B, a proprietary, scalable, “off-the-shell” cellular therapy, is made from living cells called medicinal signaling cells, or MSCs, that are isolated from fresh bone marrow tissue that has been donated by adult donors aged 18 to 45.
Lomecel-B, which also remains in development for other conditions such as aging-related frailty and hypoplastic left heart syndrome, first showed promise in the phase 2a CLEAR MIND study (NCT05233774). Topline results announced earlier this year showed that the agent met its primary end point of safety, with slowing of disease worsening in patients with mild AD. At the end of the 39-week treatment period, investigators reported no new safety concerns, in addition to no cases of amyloid-related imaging abnormalities, no clinically asymptomatic microhemorrhages on MRI, and no notable changes in laboratory evaluations and electrocardiogram.3
"The RMAT designation is an important milestone for Longeveron and the Lomecel-B program that recognizes the potential of our cellular therapy to have a positive impact on patients afflicted with this devastating disease," Joshua Hare, co-founder, chief science officer, and chairman of the board at Longeveron, said in a statement.2 "AD is a neurodegenerative disorder that leads to progressive memory loss and death and currently has very limited therapeutic options. In the CLEAR MIND Phase 2a clinical trial, Lomecel-B demonstrated an overall slowing/prevention of disease worsening compared to placebo. The trial achieved the primary safety and secondary efficacy end points and showed statistically significant improvements in pre-specified clinical and biomarker endpoints in specific Lomecel-B groups compared with placebo."
FDA Clears Phase 2 MoMeNtum Trial of DNTH103 in Multifocal Motor Neuropathy
A couple of days later, on July 12, the FDA cleared Dianthus Therapeutics’ investigational new drug application (IND) for its phase 2 MoMeNtum trial assessing DNTH103, an investigational monoclonal antibody, in patients with multifocal motor neuropathy (MMN). Topline results for the double-blind, placebo-controlled trial are expected in the second half of 2026.4
MoMeNtum, a global study, will assess the efficacy and safety of DNTH103 in 36 patients with MMN. Following determination of Ig dependency and responsiveness, patients will be randomly assigned to either placebo or DNTH103, delivered subcutaneously, every 2 weeks, for a 17-week period. After the initial treatment period, patients will have the opportunity to enter a long-term, 52-week open-label extension, where additional safety and efficacy data will be collected.
"Pre-clinical and clinical evidence support the classical pathway’s role in the pathology seen in MMN," Simrat Randhawa, MD, chief medical officer at Dianthus Therapeutics, said in a statement.4 "DNTH103 is a potent and highly selective inhibitor of active C1s resulting in classical pathway inhibition, without inhibiting the alternative and lectin pathways that are critical in the defense against infection. The Dianthus medical team and our MMN steering committee are excited to investigate the potential benefits DNTH103 may bring to patients with MMN."
FDA Grants Regenerative Medicine Advanced Therapy Designation to Kyverna's KYV-101 for Refractory Stiff-Person Syndrome
A few days later, on July 15, the FDA granted RMAT designation to Kyverna Therapeutics’ KYV-101, an investigational CD19-directed chimeric antigen receptor (CAR) T-cell therapy, for the treatment of patients with refractory stiff-person syndrome (SPS).5
About a month prior, in June 2024, the company announced data that revealed KYV-101 improved the condition of a patient with SPS on several measurements including walking speed.6 Published in the Proceedings of the National Academy of Sciences, the data came from a case study featuring a single patient treated with the agent. The patient, a 59-year-old woman whose first symptoms of SPS appeared in 2014, was treated in Germany under a named-patient use basis. The patient was treated with a single dose of 1x108 CAR T-cells at baseline after having undergone a lymphodepletion regimen with fludarabine and cyclophosphamide, and was then followed for 6 months.7
"As a physician dedicated to optimizing diagnosis and treatments for patients with autoimmune neurological disorders, I am grateful to be able to witness and contribute to the advancement of treatments and patient outcomes in stiff person syndrome via collaborative research efforts with leading players in the field and the support of the FDA oversight," Amanda Piquet, MD, the director of the Autoimmune Neurology Program at University of Colorado Anschutz Medical Campus, told NeurologyLive®.
FDA Grants Fast Track Designation for Longeveron’s Lomecel-B in Mild Alzheimer Disease
A couple of days later, on July 17, the FDA granted Longeveron’s Lomecel-B allogeneic cellular investigational therapy fast track designation for the treatment of mild AD. The granted designation was based on positive topline data reported from the phase 2a CLEAR MIND trial (NCT05233774), which were presented at the 2024 Alzheimer’s Association International Conference, July 28 to August 1, in Philadelphia, Pennsylvania.8
Topline results from the CLEAR MIND study announced earlier this year showed that the agent met its primary end point of safety, with slowing of disease worsening in patients with mild AD. At the end of the 39-week treatment period, investigators reported no new safety concerns, in addition to no cases of amyloid-related imaging abnormalities, no clinically asymptomatic microhemorrhages on MRI, and no notable changes in laboratory evaluations and electrocardiogram.9
“Fast track designation is another important milestone for Longeveron and Lomecel-B, which, along with the recent granting of RMAT designation, recognizes the critical need to quickly advance novel, safe and effective investigational treatments for AD, which has a devastating impact on patients and their families,” Wa’el Hashad, chief executive officer at Longeveron, said in a statement.8
FDA Clears IND Application for Myogenica’s MyoPAXon in Muscular Dystrophy
On the same day, July 17, the FDA granted the approval of Myogenica’s IND application to study MyoPAXon, an induced pluripotent stem cell-derived muscle stem cell product to regenerate skeletal muscle. The company noted that a proposed early-stage clinical trial would assess the safety, tolerability, and engraftment of the therapy among patients with Duchenne muscular dystrophy (DMD).10
The pending trial, led by Peter Kang, MD, FAAN, FAAP, a pediatric neuromuscular neurologist and director of the Greg Marzolf Jr. Muscular Dystrophy Center at the University of Minnesota Medical School, plans to administer intra-muscular injections of MyoPAXon in adult patients with nonambulatory DMD. Kang and colleagues in the trial will then monitor any potential site reactions or immune response and investigate the presence of dystrophin-producing myofibers.
"I was thrilled to see this milestone in testing cell therapies for muscular dystrophy in humans. There is enormous potential to provide lasting relief for patients with muscular dystrophy. Our planned initial study will focus on safety considerations, and we will be injecting MyoPAXon into a small foot muscle to assess safety and tolerability of various doses," Kang told NeurologyLive®. "What makes MyoPAXon distinct is that it has the exciting potential for muscle regeneration. Once injected, the MyoPAXon cells can survive indefinitely and thus yield long term beneficial effects."
FDA Clears IND for CAR-T Cell Therapy Equecabtagene Autoleucel in Multiple Sclerosis
A few days later, on July 23, the FDA cleared IASO Biotechnology’s IND to test equecabtagene autoleucel in patients with multiple sclerosis (MS). Equecabtagene autoleucel, an autologous anti-B cell maturation antigen (BCMA)-directed CAR-T cell therapy, is also in development for other autoimmune conditions, including myasthenia gravis (MG), neuromyelitis optica spectrum disorder (NMOSD), and multiple myeloma.11
The company did not release any details as to the next steps of its clinical development, or when it may begin clinical trials involving patients with MS. This was the second FDA IND approval of equecabtagene autoleucel for the treatment of autoimmune diseases in 2024, following refractory MG in early April.
"In an investigator initiated trial (IIT) conducted in China, Eque-cel has shown promising efficacy in 6 autoimmune diseases. The IND approval of Eque-cel in the treatment of MS from the FDA is another strong evidence of IASO Bio's ongoing dedication and technological advancements in the treatment of autoimmune diseases," Yongke Zhang, MD, PhD, chief scientific officer at IASO Bio, said in a statement.11 "We will continue to adhere to the research and development philosophy that prioritizes clinical value to address unmet clinical needs and will place great importance on implementing a global strategy. Through close collaboration and in-depth exchanges with international clinical research institutions, we aim to accelerate the development and commercialization of more innovative drugs, bringing greater benefits to patients worldwide."
FDA Grants Intranasal Foralumab Fast Track Designation for Nonactive Secondary Progressive Multiple Sclerosis
A day later, on July 24, the FDA granted fast track designation to Tiziana Life Sciences’ intranasal foralumab, a fully human anti-CD3 monoclonal antibody, for the treatment of nonactive secondary progressive MS (na-SPMS).12 Intranasal foralumab is designed to bind to T cell receptors and dampens inflammation by modulating T cell function, thereby suppressing effector features in multiple immune cell subsets.
As of July 2024, 10 patients with na-SPMS were dosed in an open-label intermediate sized Expanded Access (EA) program, all of whom either improved or showed stability of disease across 6 months. Recently, the FDA allowed an additional 20 patients to be enrolled in this EA program, increasing the cohort to a total of 30 patients.13 The company noted that patients with na-SPMS who were not eligible for the phase 2a trial (NCT06292923) assessing the treatment, initiated in November 2023, were considered for this EA program.
"We are thrilled to receive fast track designation from the FDA for intranasal foralumab for the treatment of MS," Gabriele Cerrone, chairman, acting CEO and founder at Tiziana Life Sciences, said in a statement.12 "This designation underscores the potential of foralumab to address critical unmet needs in the treatment of neurodegenerative diseases. We are committed to advancing this promising therapy as quickly as possible to benefit patients."
FDA Approves Expanded Indication for Cerliponase Alfa to Treat CLN2 Disease in Children Under 3 Years
On the same day, July 24, the FDA approved an expanded indication for BioMarin Pharmaceutical's cerliponase alfa (Brineura), a therapy for children with neuronal ceroid lipofuscinosis type 2 (CLN2 disease, or Batten disease), to treat patients of all ages, including those younger than 3 years old. In addition, the therapy will now be available to all patients, including those who are symptomatic or asymptomatic.14
The supplemental biologic drug application (sBLA) was supported by data from Study 190-203 (NCT02678689), a phase 2 open-label trial in children with CLN2 whose siblings were those in previously completed studies, Studies 201 and 202. In the 3-year study, treatment with cerliponase alfa resulted in reduced decline in motor function and delayed disease onset, including among those with CLN2 less than 3 years of age. In addition, the therapy showed a safety profile that was similar to that observed in prior studies, including the aforementioned Studies 201 and 202.
"Today's approval represents a significant step forward in enabling children to be treated with BRINEURA as early as possible, when we can have the greatest impact in altering the natural course of disease," Hank Fuchs, MD, president of Worldwide Research and Development at BioMarin, said in a statement.14 "We know that every day counts for families affected by serious genetic conditions such as CLN2 disease, which is characterized by a rapid onset of neurodegenerative symptoms. We have been working diligently since BRINEURA's initial approval to support this expanded use in children of all ages, even before they begin to show symptoms.”
FDA Grants FDA Fast Track Designation to Anti-pTau Agent JNJ-2056 for Alzheimer Disease
Another day later, on July 25, the FDA granted fast track designation to AC Immune SA’s anti-phosphorylated tau (pTau) immunotherapy candidate JNJ-2056, formerly known as ACI-35.030, in development for the treatment of patients with AD. The company also announced that it is recruiting participants for its phase 2b ReTain trial, which is designed to test whether JNJ-2056 has a disease-modifying effect that can delay or prevent the onset of cognitive impairment or other clinical symptoms in patients with preclinical AD.15
Launched in December 2023, the phase 2b ReTain trial, a multicenter, double-blind, placebo-controlled study, is expected to include 500 patients with preclinical AD who are randomly assigned 1:1 to a single dose of JNJ-2056 or placebo for a maximum of 4 years.15 Change in Preclinical AD Cognitive Composite 5 (PACC-5) score, which combines tests of episodic memory, timed executive function, and global cognition, will serve as the primary end point. The key secondary efficacy end point will evaluate the effect of JNJ-2056 on the propagation and/or accumulation of Tau pathology compared with placebo, as measured by Tau PET imaging.
“Fast track designation is an important recognition of the differentiation and potential value for patients of our anti-pTau active immunotherapy, ACI-35.030. The phase 2b ReTain study is the first time any active immunotherapy is being tested in a preclinical AD population. We believe this modality has the potential to offer therapeutic advantages, as well as benefits in terms of convenience and access,” Andrea Pfeifer, PhD, CEO at AC Immune SA, said in a statement.14 “Fast track designation offers opportunities for more efficient development and regulatory review. More importantly, this underscores and validates the potential therapeutic impact of an active immunotherapy specifically targeting pTau, the key pathologic species of Tau protein.”
FDA Approves New-Generation Acetylcholinesterase Inhibitor ALPHA-1062 for Mild-to-Moderate Alzheimer Disease
At the end of the month, on July 29, the FDA approved Alpha Cognition’s ALPHA-1062 (Zunveyl), a prodrug of an approved acetylcholinesterase inhibitor (AChEI), galantamine, as a treatment for patients with mild-to-moderate AD. ALPHA-1062, a delayed-release oral tablet formulation, is considered a new-generation AChEI inhibitor, with expected minimal gastrointestinal adverse events (AEs).16
The approval was based on results from 4 studies demonstrating the bioequivalence of ALPHA-1062 to galantamine and galantamine extended-release (ER). Across those studies, only 2% of treated patients had AEs from treatment, with no cases of insomnia observed.17ALPHA-1062 is absorbed in the small intestine as an insert drug. Binding with AChE in the gastrointestinal nervous system is blocked by the addition of a benzyl ester to galantamine. This reduces overstimulation of local neurons, reduces gastrointestinal AEs, and increases bioavailability.
“I am very excited about the approval of Zunveyl, which we believe offers better tolerability for patients with AD. We have always believed in the efficacy of galantamine but have been limited in its use because of tolerability issues. To now have an agent with the efficacy of galantamine, but that also offers the hope of better tolerability, will provide physicians a great option to treat patients,” Elaine Peskind, MD, the Friends of Alzheimer’s Research Professor of Psychiatry at the University of Washington School of Medicine, said in a statement.16 “This advancement marks a meaningful step forward in improving the quality of life for those living with Alzheimer and their families. As a geriatric psychiatrist specializing in AD, I am eager to incorporate this new treatment into our practice and see the positive difference it will make.”
