FDA Action Update, January 2024: Approvals, Clearances and Requests

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

The FDA was busy in January 2024, making a number of decisions on potential new therapeutic agents including clearances for clinical trials, granting approvals, and issuing a response letter.

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 Clears Phase 2 KYSA-7 Study of CAR T-Cell Therapy in Refractory Progressive Multiple Sclerosis

Earlier in the month, on January 3, the FDA cleared Kyverna Therapeutics’ investigational new drug application (IND) to test KYV-101, a CAR T-cell therapy, in patients with refractory progressive multiple sclerosis (MS), a disease for which there are limited available therapies. The approved phase 2 open-label trial will target a large patient demographic to evaluate the effectiveness and safety of the agent in this patient population.1

The IND clearance is the 7th for KYV-101, which is also currently being assessed in patients with lupus nephritis and soon to be evaluated in trials of systemic sclerosis and myasthenia gravis. The autologous, fully human CD19 CAR T-cell product candidate was previously assessed in a phase 1 trial (NCT02659943) in oncology, using patients with B cell lymphoma. Published in Nature in 2020, that small-scale study of 20 individuals met its primary objective of safety and feasibility.2

"This approval is a critically necessary step that paves the way to enroll patients with treatment-refractory progressive MS for whom there are no currently available treatment options in the KYSA-7 trial," Bruce Cree, MD, PhD, MAS, clinical research director and professor of clinical neurology at the University of California, San Francisco, said in a statement.1 "This study offers participants a new hope for arresting relentless disability worsening and a potentially durable, treatment-free remission."

FDA Clears Phase 2 KYSA-7 Study of CAR T-Cell Therapy in Refractory Progressive Multiple Sclerosis

FDA Grants Approval of Darmiyan's BrainSee Test for Predicting Progression of Alzheimer Disease

About a week later, on January 12, the FDA granted the first of its kind approval for Darmiyan's BrainSee, a software platform that may predict the progression of amnestic mild cognitive impairment (aMCI) to Alzheimer disease (AD) in patients, based on a combined artificial intelligence (AI) assessment of brain MRI and cognitive assessments.3

Originally in 2021, the FDA previously granted breakthrough designation for BrainSee. The test is the first clinical application of the company's patented core proprietary technology based on over 40 years of research, powered by advanced whole-brain image analysis and medical AI. Thus, the company noted that it is a highly scalable and fully automated program that can generate an objective score to predict the likelihood of progression from aMCI to AD in 5 years.

"Our vision is to redefine brain health screening and monitoring standards and impact the lives of patients and their family members in a meaningful way,” Padideh Kamali-Zare, PhD, the founder and CEO of Darmiyan, said in a statement.3 “BrainSee is the first product of this vision, backed by our solid technological infrastructure that is capable of driving further transformations and scalable innovations in the brain health landscape.”

FDA Grants Approval of Darmiyan's BrainSee Test for Predicting Progression of Alzheimer Disease

FDA Clears Aruna Bio’s Exosome AB126 for Clinical Trials in Neurological Indication

A few days later, on January 16, the FDA cleared Aruna Bio’s IND application for the company’s lead candidate AB126, an unmodified neural-derived exosome, according to a new announcement.4 This clearance by the agency paves the way for investigating AB126 in a phase 1b/2a clinical trial among patients with acute ischemic stroke, which the company noted is expected to initiate in the first half of 2024.

AB126 has intuitive ability to cross the blood-brain barrier and modulate inflammasome in the central nervous system (CNS) by action of anti-inflammatory and neuroprotective mechanisms, giving it the potential to treat a range of neurodegenerative disorders, according to Aruna Bio. In addition, the company noted that its neural exosome platform can be combined with therapeutics, such as small molecules, small interfering RNAs, and proteins.

“We look forward to building on the preclinical findings that showed AB126 may diminish neuroinflammation, and potentially foster neuroprotection, and promote neuroregeneration,” principal investigator Sean Savitz, MD, professor of neurology and the director of the Institute for Stroke and Cerebrovascular Disease at The University of Texas Health Science Center at Houston, said in a statement.4

 FDA Clears Aruna Bio’s Exosome AB126 for Clinical Trials in Neurological Indication

FDA Approves Takeda’s Immune Globulin Infusion, Hyqvia, for Chronic Inflammatory Demyelinating Polyneuropathy

On the same day, January 16, the FDA approved immune globulin (IG) infusion 10% (human) with recombinant human hyaluronidase (Hyqvia; Takeda Pharmaceuticals), a liquid medicine, as maintenance therapy for adults with chronic inflammatory demyelinating polyneuropathy (CIDP) to prevent relapse of neuromuscular disability and impairment. Hyqvia is the only FDA-approved combination of IG and hyaluronidase, which makes it a facilitated subcutaneous immunoglobulin (SCIG) infusion.5

The approval was based on findings from the randomized, double-blinded, placebo-controlled ADVANCE-CIDP 1 trial (NCT02549170) and the single-arm, open-label, extension ADVANCE-CIDP 3 study (NCT02955355) that assessed the efficacy and safety of Hyqvia in adults with CIDP. The analysis of the primary end point among 122 with CIDP from ADVANCE-CIDP 1 showed a statistical difference between the relapse rates in the Hyqvia group (n = 57; 14.0%) compared with the placebo group (n = 65; 32.3%), which was significant (P = .0314).

“With the FDA approval of Hyqvia for CIDP, which builds on our expertise in rare neuroimmunological and neuromuscular disorders, we can now offer a personalized maintenance treatment option for adults with this debilitating disease,” Giles Platford, president of Takeda’s Plasma-Derived Therapies Business Unit, said in a statement.5 “Research and clinical experience have shown that IG therapy is effective as maintenance treatment in adults with CIDP, and we hope that this approval for Hyqvia is the first of several around the world as we strive to deliver our broad and diverse IG portfolio to more people with complex neuroimmunological diseases.”

FDA Approves Takeda’s Immune Globulin Infusion, Hyqvia, for Chronic Inflammatory Demyelinating Polyneuropathy

FDA Issues Complete Response Letter for Satsuma’s DHE Nasal Powder STS101 to Treat Acute Migraine

A couple of days later, on January 18, the FDA issued a complete response letter (CRL) to Satsuma Pharmaceuticals’ for STS101, a dihydroergotamine (DHE) nasal powder therapy in development as a treatment for adults with acute migraine.6

In its release, the FDA noted no concerns related with the clinical trial results, including the safety of STS101, and did not request additional clinical trials. However, the agency provided additional comments primarily related to formulation (Chemistry, Manufacturing, and Control - CMC). The company noted that it will engage in discussions with the agency promptly and consider reapplying for market approval.

"We are committed to collaborating with the FDA, addressing their feedback swiftly, and making every effort to deliver STS101 to patients in the United States as soon as possible," Ryoichi Nagata, MD, PhD, FFPM, president and CEO at Satsuma Pharmaceuticals, said in a statement.6

 FDA Issues Complete Response Letter for Satsuma’s DHE Nasal Powder STS101 to Treat Acute Migraine

FDA Clears IND for Vanda’s Antisense Agent VCA-894A in Charcot-Marie-Tooth Disease Type 2S

Less than a week later, on January 23, the FDA approved an IND to study Vanda Pharmaceuticals’ investigational agent VCA-894A, an antisense oligonucleotide (ASO), in patients with Charcot-Marie-Tooth disease type 2S (CMT2S).7

In the update, Vanda did not release any details on the design of the potential trial and how it would go about assessing the candidate therapy. VCA-894A has a mechanism of action that specifically targets a cryptic splice site variant within immunoglobulin mu-binding protein 2 (IGHMBP2), otherwise considered the root cause of CMT2S. In mid-2023, the agent received orphan drug designation by the FDA.

"This is an important milestone in the pursuit of personalized medicine, which has the potential to enable the development of treatments tailored to one's genetic variants, in this case specifically for a patient with CMT2S causing genetic mutations," Mihael H. Polymeropoulos, MD, president, chief executive officer, and chairman of Vanda’s Board, said in a statement.7

FDA Clears IND for Vanda’s Antisense Agent VCA-894A in Charcot-Marie-Tooth Disease Type 2S

FDA Approves Takeda’s Immune Globulin Infusion, Gammagard Liquid, for Chronic Inflammatory Demyelinating Polyneuropathy

A few days later, on January 29, Following the approval of Takeda's Hyqvia, the FDA has approved the company's immune globulin (IG) infusion 10% (human) (Gammagard Liquid) as an intravenous immunoglobulin (IVIG) therapy to improve neuromuscular disability and impairment in adults with CIDP.8

The approval is based on results from the prospective, open-label, single-arm, multicenter ADVANCE-CIDP 2 trial (NCT02549170) which comprised of adults with CIDP who developed a relapse in the previously-completed, placebo-controlled ADVANCE-CIDP 1 trial evaluating efficacy, safety and tolerability of Hyqvia. Among 18 patients with CIDP in the trial, findings showed a 94.4% responder rate (95% CI, 74.2% to 99.0%), suggesting an improvement in functional disability.

“As the standard of care for the treatment of CIDP, IG therapy is thought to help normalize compromised immune systems through immunomodulatory mechanisms,” Mamatha Pasnoor, MD, professor in the Department of Neurology at the University of Kansas Medical Center, said in a statement.8 “Because CIDP is a progressive and complex disease, multiple treatment options are needed, and clinicians now have an additional therapy that can help adults with CIDP manage their disease.”

FDA Approves Takeda’s Immune Globulin Infusion, Gammagard Liquid, for Chronic Inflammatory Demyelinating Polyneuropathy
REFERENCES
1. Kyverna’s KYV-101 receives US FDA clearance for treatment of patients with refractory, progressive multiple sclerosis in the KYSA-7 phase 2 trial. News release. January 3, 2024. Accessed February 7, 2024. https://www.prnewswire.com/news-releases/kyvernas-kyv-101-receives-us-fda-clearance-for-treatment-of-patients-with-refractory-progressive-multiple-sclerosis-in-the-kysa-7-phase-2-trial-302025646.html
2. Bruno JN, Lam N, Vanasse D, et al. Safety and feasibility of anti-CD19 CAR T cells with fully human binding domains in patients with B-cell lymphoma. Nature. 2020;26:270-280. doi:10.1038/s41591-019-0737-3
3. Darmiyan Receives FDA Approval for BrainSee, the First Prognostic Test for Predicting Likelihood of Progression to Alzheimer's Dementia. News Release. Darmiyan. Published January 12, 2024. Accessed February 7, 2024. https://www.newswise.com/articles/darmiyan-receives-fda-approval-for-brainsee-the-first-prognostic-test-for-predicting-likelihood-of-progression-to-alzheimer-s-dementia
4. Aruna Bio Announces FDA Clearance of IND for Lead Program AB126, Enabling the First Exosome to Enter in Human Clinical Trials for a Neurological Indication. News Release. Aruna Bio. Published January 16, 2024. Accessed February 7, 2024. https://www.globenewswire.com/en/news-release/2024/01/16/2809846/0/en/Aruna-Bio-Announces-FDA-Clearance-of-IND-for-Lead-Program-AB126-Enabling-the-First-Exosome-to-Enter-in-Human-Clinical-Trials-for-a-Neurological-Indication.html
5. U.S. FDA Approves Takeda’s HYQVIA® as Maintenance Therapy in Adults with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). News Release. Takeda. Published January 16, 2024. Accessed February 7, 2024. https://www.takeda.com/en-us/newsroom/news-releases/2024/us-fda-approves-takedas-hyqvia-as-maintenance-therapy-in-adults-with-chronic-inflammatory-demyelinating-polyneuropathy-cidp
6. Satsuma Pharmaceuticals Receives Complete Response Letter (CRL) from the U.S. FDA Regarding New Drug Application for STS101, a Nasal Powder for Migraine. News Release. Satsuma Pharmaceuticals. January 18, 2024. Accessed February 7, 2024. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.nikkei.com/markets/ir/irftp/data/tdnr/tdnetg3/20240118/eixd95/140120240118516377.pdf
7. Vanda Pharmaceuticals receives FDA approval to proceed with investigational new drug VCA-894A, a novel antisense oligonucleotide candidate for the treatment of Charcot-Marie-Tooth disease, type 2S. news release. Vanda Pharmaceuticals. January 23, 2024. Accessed February 7, 2024. https://www.prnewswire.com/news-releases/vanda-pharmaceuticals-receives-fda-approval-to-proceed-with-investigational-new-drug-vca-894a-a-novel-antisense-oligonucleotide-candidate-for-the-treatment-of-charcot-marie-tooth-disease-type-2s-302042063.html
8. Takeda’s GAMMAGARD LIQUID® Approved by U.S. FDA for Adults with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). News Release. Takeda. Published January 29, 2024. Accessed February 7, 2024. https://www.takeda.com/newsroom/newsreleases/2024/Takedas-GAMMAGARD-LIQUID-Approved-for-Adults-with-CIDP-in-United-States/
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