FDA Action Update, May 2024: Approvals, Designations, and Labeling Update

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Catch up on any of the neurology news headlines you may have missed over the course of May 2024, compiled all into one place by the NeurologyLive® team.

The FDA was busy in May 2024, making a number of decisions on potential new therapeutic agents including approvals, the removal of a clinical hold, designations, and new labeling.

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 Grants Breakthrough Therapy Designation for AOC 1001 in Myotonic Dystrophy Type 1

Early in the month, on May 8, the FDA granted breakthrough therapy designation to AOC 1001 (Avidity Biosciences), an investigational treatment based on Avidity’s Antibody Oligonucleotide Conjugates (AOC) platform, for the treatment of myotonic dystrophy type 1 (DM1).1 The therapy, also known as del-desiran, consists of a monoclonal antibody that binds to the transferrin receptor 1 conjugated with a small interfering RNA targeting DMPK mRNA, the underlying cause of DM1.

"We are pleased that the FDA has granted breakthrough therapy designation to del-desiran for DM1, underscoring the potential of del-desiran to be an effective treatment and the urgency of bringing this treatment to patients living with DM1," Sarah Boyce, president and chief executive officer at Avidity, said in a statement.1 "Initiation is underway for our global phase 3 HARBOR study as we focus on rapidly advancing del-desiran for patients living with DM1, who currently have no treatment options to address the underlying cause of this devastating rare muscle disease."

In March 2024, the company announced additional data from the long-term, open-label extension (OLE) of the phase 2 MARINA trial (NCT05479981) which further highlighted AOC 1001’s potential as a treatment for patients with DM1.2 These results were recently presented at the 2024 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, held March 3-6, in Orlando, Florida, by lead author John W. Day, MD, PhD, medical advisor and care center director at the MDA.3 The phase 3 HARBOR study, a subsequent trial to MARINA, is expected to initiate in the second quarter of 2024.

FDA Grants Breakthrough Therapy Designation for AOC 1001 in Myotonic Dystrophy Type 1

Cross-Compatibility Issues With Autoinjectors Highlighted in New FDA Labeling Update of Glatiramer Acetate Injection

About a week later, on May 16, the FDA issued an update to the labeling of glatiramer acetate injection products, with a new warning label that highlights cross-compatibility issues with the use of autoinjectors. In the update, the agency also alerted patients and health care professionals that some specific glatiramer acetate injection therapies may be administered using an optional compatible autoinjector, while other glatiramer acetate injection products must only be injected using the prefilled syringe.4

The increased risk for medications errors, such as a missed dose or administration of a partial dose, was the basis behind the updated labeling for these autoinjectors. The agency noted it will not further update the table of glatiramer acetate injection products and their optional compatible autoinjector devices included in the CDER Alert originally issued in August 2022.

In the update, the agency wrote, "Patients can continue to confirm the compatibility of their autoinjector by speaking with their health care professional, visiting the drug manufacturer's patient information website, contacting the drug manufacturer for more information, or referring to the autoinjector labeling. Patients should also continue to confirm their autoinjector is compatible each time they receive a new prescription for a glatiramer acetate injection drug product."4

Cross-Compatibility Issues With Autoinjectors Highlighted in New FDA Labeling Update of Glatiramer Acetate Injection

FDA Grants Fast Track Designation to PET Tau Tracer APN1607 for Progressive Supranuclear Palsy

A couple of days later, on May 20, the FDA granted fast track designation to Aprinoia’s APN-1607, a first-in-class radioactive diagnostic PET imaging tracer of tau aggregates, for patients with suspected progressive supranuclear palsy (PSP). APN-1607 is currently being tested in a global phase 3 trial to evaluate its performance as a biomarker for the early diagnosis of PSP.5

Currently, there are no FDA-approved diagnostic markers for PSP or any other rare tau-related disorders such as frontotemporal dementia. APN-1607, a radioactive fluorinated molecule developed to visualize and quantify 3R and 4R tau aggregates by PET imaging, has already previously received orphan drug designation and has been clinically utilized in over 3000 patients through investigator-initiated and sponsor trials.

"We are very pleased with the FDA’s decision to grant APN-1607 Fast Track Designation as it underscores the significant unmet medical need for a diagnostic marker for the early diagnosis of PSP and potentially other tau-related disorders, including Alzheimer’s disease,” Brad Navia, MD, chief medical officer at Aprinoia, said in a statement.5 "APN1607 is a unique imaging agent as it was designed to detect specific forms of tau implicated in PSP and other related disorders. Sadly, patients with PSP can remain undiagnosed for several years as it is often confused with other Parkinson’s like disorders, especially during the early stages."

FDA Grants Fast Track Designation to PET Tau Tracer APN1607 for Progressive Supranuclear Palsy

FDA Removes Partial Clinical Hold on Nomlabofusp Program for Friedreich Ataxia

On the same day, May 20, the FDA removed the partial clinical hold previously placed on the clinical program of Larimar Therapeutics' nomlabofusp, formally known as CTI-1601, for the treatment of patients with Friedreich Ataxia (FA) following the review of data from a phase 2 dose exploration study (NCT05579691).6 The data reviewed included findings from both the 25 mg and 50 mg cohorts in participants who received daily dosing of nomlabofusp for 14 days followed by every other day dosing until day 28.

In the phase 2 study, results demonstrated that nomlabofusp, a novel protein replacement therapy aimed to address the root cause of FA through delivery of frataxin to mitochondria, was generally well-tolerated among participants throughout the 4-week treatment period. The treatment revealed a predictable pharmacokinetic profile and showed a dose-dependent increase in frataxin levels in skin and buccal cells. All participants with quantifiable levels at baseline and day 14 in the 50 mg cohort achieved frataxin levels in skin cells over 33% of the average level reported in healthy volunteers at day 14, and 3 patients achieved levels greater than 50% of the average healthy volunteer level.7

“We are very excited the FDA has removed the partial clinical hold on our nomlabofusp program following review of our phase 2 data. Helping patients with FA is our top priority and we appreciate the attention and thorough review by the FDA of all submitted data,” Carole Ben-Maimon, MD, president, and chief executive officer at Larimar, said in a statement.6 “Importantly, we are now cleared to dose escalate to the 50 mg dose in our ongoing open label extension (OLE) study which we plan to do following further characterization of frataxin PD at the 25 mg dose. The OLE study is evaluating the long-term safety as well as frataxin levels following daily administration of nomlabofusp and we look forward to interim data in the fourth quarter of the year.”

FDA Removes Partial Clinical Hold on Nomlabofusp Program for Friedreich Ataxia

Transposon Therapeutics’ TPN-101 for Progressive Supranuclear Palsy Gets Fast Tracked

A day later, on May 21, the FDA granted fast track designation to Transposon Therapeutics’ TPN-101, an investigational therapy that inhibits the LINE-1 reverse transcriptase that promotes LINE-1 replication, for PSP, according to a recent announcement.8 The designation was supported by data from a phase 2a study (NCT04993768) assessing TPN-101 in patients with PSP.

In the trial, TPN-101 reduced levels of neurofilament light chain (NfL) and showed dose-related reductions in interleukin 6 (IL-6) cytokine levels as well as osteopontin levels at 48 weeks. Patients who switched to 400-mg TPN-101 from placebo reported a reduction of NfL in the cerebrospinal fluid (CSF) from weeks 24 to 48 similar to that observed in the patients who received the 400-mg dose from weeks 1 to 24. Those treated with 400-mg TPN-101 for the entire 48-week treatment period had no increase of NfL levels in the CSF from weeks 1 to 48.9

"Fast track designation for TPN-101 is an important acknowledgement by the FDA of the critical need to find an effective treatment for PSP, a rare and devastating neurological disorder with no approved treatment options," Dennis Podlesak, chairman and chief executive officer at Transposon, said in a statement.8 "We look forward to working collaboratively with the FDA to advance the development of TPN-101 as rapidly as possible for the treatment of PSP and other neurodegenerative diseases including ALS and Alzheimer disease."

Transposon Therapeutics’ TPN-101 for Progressive Supranuclear Palsy Gets Fast Tracked

FDA Approves One Pill, Once-Daily Tablets of Deutetrabenazine for Tardive Dyskinesia, Chorea

At the end of the month, on May 29, the FDA approved a new one-pill, once-daily tablet administration option for deutetrabenazine (Austedo XR; Teva Pharmaceuticals), a medication for tardive dyskinesia and chorea associated with Huntington disease (HD). Deutetrabenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor, is now available in 4 tablet strengths (30, 36, 42, and 48 mg), adding on to its original dosing options of 6 mg, 12 mg, and 24 mg.10

The medication was originally approved as a twice-daily treatment for chorea associated with HD in April 2017 and later had its label expanded in August 2017 to include the treatment of tardive dyskinesia. In February 2023, the FDA approved a once-daily, extended-release formulation of the agent, further allowing for more administration flexibility and improved adherence.11

"Since our launch of Austedo in 2017, we have been committed to helping people living with TD and HD chorea treat these chronic, involuntary movements,” Dell Faulkingham, senior vice president, and head of Innovative Medicines at Teva, said in a statement.10 "Austedo, backed by the longest efficacy and tolerability data to date, has continued to evolve—having received approval for Austedo XR, our once-daily extended-release formulation in February 2023. This latest milestone offers a streamlined treatment regimen for clinically therapeutic doses with the broadest dosing flexibility."

FDA Approves One Pill, Once-Daily Tablets of Deutetrabenazine for Tardive Dyskinesia, Chorea

FDA Approves Dose Expansion of Catalyst's Amifampridine for Lambert-Eaton Myasthenic Syndrome

A day later, on May 30, the FDA approved Catalyst Pharmaceuticals’ supplemental new drug application (sNDA) for a higher maximum daily dose of its potassium channel blocker amifampridine (Firdapse) from 80 mg to 100 mg for the treatment of adults and pediatric patients weighing more than 45 kg with Lambert-Eaton myasthenic syndrome (LEMS), a rare autoimmune neuromuscular disorder characterized primarily by muscle weakness of the limbs.12 This decision provides an additional indicated dosage option for patients with LEMS who might benefit from a daily dosage greater than 80 mg of amifampridine.

“We are pleased to receive the approval for the increased maximum daily dose of Firdapse,” Richard J. Daly, MBA, president and CEO of Catalyst, said in a statement.12 “This pivotal achievement further underscores our dedication to meeting the evolving needs of LEMS patients and their healthcare providers. We believe that this milestone will have a meaningful impact on the lives of LEMS patients, offering a new level of flexibility in treatment while aligning with our overarching mission to optimize LEMS patient outcomes.”

In November 2018, the FDA approved the drug for patients with LEMS aged 17 and older and approved the expanded use of the treatment to include patients as young as age 6 in 2022. The treatment approval for adults was based on findings from a pair of phase 3 trials, LMS-002 (NCT01377922) and LMS-003 (NCT02970162) which demonstrated the efficacy of amifampridine, clinically relevant differences over placebo in Quantitative Myasthenia Gravis (QMG) score.13

FDA Approves Dose Expansion of Catalyst's Amifampridine for Lambert-Eaton Myasthenic Syndrome

FDA Grants Regenerative Medicine Advanced Therapy Designation to Parkinson Cell Therapy Candidate Bemdaneprocel

On the last day of the month, on May 31, the FDA granted BlueRock Therapeutics’ bemdaneprocel, an investigational cell therapy for Parkinson disease (PD), a regenerative medicine advanced therapy (RMAT) designation.14 Bemdaneprocel is designed to reform neural networks that have been severely impacted by the disease and currently is the most clinically advanced investigational cell therapy in the United States for the treatment of PD.

The company recently presented positive 18-month data on bemdaneprocel from its phase 1 study (NTC04802733) at the 2024 International Conference on Alzheimer’s and Parkinson’s Disease (AD/PD), held March 5-9, in Lisbon, Portugal. Conducted by lead author Claire Henchcliffe, MD, chair of the department of neurology at the University of Califorina, Irvine, and colleagues, the results showed that the agent was safe and well-tolerated, with treated patients demonstrating improvements in ON and OFF time over that period.15

“We are excited about the positive data from the bemdaneprocel phase 1 clinical trial and believe it has great potential to help patients living with PD regain functions they have lost to the disease,” Seth Ettenberg, president and CEO at BlueRock Therapeutics, said in a statement.14 “Now with this RMAT designation in hand, we look forward to closely collaborating with the FDA to ready this program for phase 2 clinical studies.”

FDA Grants Regenerative Medicine Advanced Therapy Designation to Parkinson Cell Therapy Candidate Bemdaneprocel
REFERENCES
1. Avidity Biosciences Receives FDA Breakthrough Therapy Designation for Delpacibart Etedesiran (AOC 1001) for Treatment of Myotonic Dystrophy Type 1. News Release. Avidity Biosciences. Published May 8, 2024. Accessed June 7, 2024. https://aviditybiosciences.investorroom.com/2024-05-08-Avidity-Biosciences-Receives-FDA-Breakthrough-Therapy-Designation-for-Delpacibart-Etedesiran-AOC-1001-for-Treatment-of-Myotonic-Dystrophy-Type-1
2. Avidity Biosciences announces positive AOC 1001 long-term data showing reversal of disease progression in people living with myotonic dystrophy type 1 across multiple end points; same key endpoints agreed for phase 3 HARBOR study. News release. Avidity Biosciences. March 4, 2024. Accessed June 7, 2024. https://www.prnewswire.com/news-releases/avidity-biosciences-announces-positive-aoc-1001-long-term-data-showing-reversal-of-disease-progression-in-people-living-with-myotonic-dystrophy-type-1-across-multiple-endpoints-same-key-endpoints-agreed-for-phase-3-harbor-trial-302078020.html
3. Johnson N, Day J, Hamel J, et al. Initial results of the phase 2 open-label extension study of AOC 1001 in adults with myotonic dystrophy type 1: MARINA-OLE. Presented at: MDA Clinical and Scientific Conference; March 3-6, 2024; Orlando, FL. POSTER POSTER T307
4. FDA alerts patients, caregivers, and health care providers of cross-compatibility issues with autoinjector devices that are optional for use with glatiramer acetate injection. News release. FDA. May 16, 2024. Accessed June 7, 2024. https://www.fda.gov/drugs/drug-safety-and-availability/fda-alerts-patients-caregivers-and-health-care-providers-cross-compatibility-issues-autoinjector?utm_medium=email&utm_source=govdelivery
5. APRINOIA Therapeutics Announces Fast Track Designation Granted by U.S. FDA to APN-1607 (florzolotau) for the Diagnosis of Progressive Supranuclear Palsy. News release. Aprinoia Therapeutics. May 20, 2024. Accessed June 7, 2024. https://finance.yahoo.com/news/aprinoia-therapeutics-announces-fast-track-120000291.html
6. Larimar Therapeutics Announces FDA has Removed Partial Clinical Hold for Nomlabofusp Program in Friedreich’s Ataxia. News Release. Larimar Therapeutics. Published May 20, 2024. Accessed June 7, 2024. https://investors.larimartx.com/news-releases/news-release-details/larimar-therapeutics-announces-fda-has-removed-partial-clinical
7. Larimar Therapeutics Reports Positive Top-line Data from Phase 2 Dose Exploration Study from 25 mg and 50 mg Cohorts of Nomlabofusp in Patients with Friedreich’s Ataxia. News Release. Published February 12, 2024. Accessed June 7, 2024. https://investors.larimartx.com/news-releases/news-release-details/larimar-therapeutics-reports-positive-top-line-data-phase-2-dose
8. Transposon Receives US FDA Fast Track Designation for TPN-101 for Progressive Supranuclear Palsy. News Release. Transposon Therapeutics. Published May 21, 2024. Accessed June 7, 2024. https://prnmedia.prnewswire.com/news-releases/transposon-receives-us-fda-fast-track-designation-for-tpn-101-for-progressive-supranuclear-palsy-302150783.html
9. Transposon Announces Final Results from a Phase 2 Study of its LINE-1 Reverse Transcriptase Inhibitor TPN-101 for the Treatment of Progressive Supranuclear Palsy and Interim Results from a Phase 2 Study of TPN-101 for the Treatment of C9orf72-Related Amyotrophic Lateral Sclerosis and/or Frontotemporal Dementia. News Release. Transposon Therapeutics. Published February 13, 2024. Accessed Accessed June 7, 2024. https://www.prnewswire.com/news-releases/transposon-announces-final-results-from-a-phase-2-study-of-its-line-1-reverse-transcriptase-inhibitor-tpn-101-for-the-treatment-of-progressive-supranuclear-palsy-and-interim-results-from-a-phase-2-study-of-tpn-101-for-the-treatmen-302060254.html
10. Teva Announces AUSTEDO® XR (deutetrabenazine) Extended-Release Tablets Now U.S. FDA Approved as a One Pill, Once-Daily Treatment Option for Clinically Therapeutic Doses (24–48 mg/day). News release. Teva Pharmaceuticals. May 29, 2024. Accessed June 7, 2024. https://www.tevapharm.com/news-and-media/latest-news/teva-announces-austedo-xr-deutetrabenazine-extended-release-tablets-now-u.s.-fda-approved-as-a-one-pil/
11. Teva Announces FDA Approval of AUSTEDO® XR (deutetrabenazine) Extended-Release Tablets, a New Once-Daily Formulation of AUSTEDO® (deutetrabenazine) Tablets. News release. Teva. February 17, 2023. Accessed June 7, 2024. https://www.businesswire.com/news/home/20230217005357/en/Teva-Announces-FDA-Approval-of-AUSTEDO%C2%AE-XR-deutetrabenazine-Extended-Release-Tablets-a-New-Once-Daily-Formulation-of-AUSTEDO%C2%AE-deutetrabenazine-Tablets
12. Catalyst Pharmaceuticals Receives U.S. FDA Approval For Increased Maximum Daily Dose For FIRDAPSE®. News Release. Catalyst Pharmaceuticals. Published June 3, 2024. Published May 30, 2024. Accessed June 7, 2024. https://ir.catalystpharma.com/news-releases/news-release-details/catalyst-pharmaceuticals-receives-us-fda-approval-increased
13. FDA approves first treatment for Lambert-Eaton myasthenic syndrome, a rare autoimmune disorder. News Release. FDA. Published November 28, 2018. Accessed June 7, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-lambert-eaton-myasthenic-syndrome-rare-autoimmune-disorder
14. BlueRock Therapeutics receives FDA Regenerative Medicine Advanced Therapy designation for Parkinson’s disease cell therapy candidate bemdaneprocel. News Release. BlueRock Therapeutics. Published May 30, 2024. Accessed June 7, 2024. https://www.bluerocktx.com/bluerock-therapeutics-receives-fda-regenerative-medicine-advanced-therapy-designation-for-parkinsons-disease-cell-therapy-candidate-bemdaneprocel/
15. Henchcliffe C, Sarva H, Lozano A, et al. Dopaminergic neuronal cell therapy for Parkinson’s disease: results from a phase 1 study of bemdaneprocel. Presented at 2023 MDS Congress; August 27-31; Copenhagen, Denmark. Abstract 65.

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