Four Neurodegenerative Trials to Watch in Q4

Doctor holding an MRI, neuro_iStock, Chinnapong

Pictured: A doctor holds an MRI of the brain/iStock, Chinnapong

Several late-stage clinical trials are expected to produce data in the final months of 2023 that could spell new approaches to treating Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease and multiple sclerosis. 

Mizuho Securities recently published a report highlighting some of the trials to watch as the year comes to a close, and BioSpace spoke with Graig Suvannavejh, managing director of equity research in biopharmaceuticals and biotechnology at the firm, to find out more.

Alzheimer’s Disease

Eisai and Biogen’s subcutaneous Leqembi

In July, the FDA fully approved Leqembi (Lecanemab), a monoclonal antibody developed by Eisai and Biogen that binds to soluble and insoluble amyloid-beta peptides to treat Alzheimer’s. Leqembi is currently administered only through intravenous injection, which limits the locations where patients can obtain treatment.

To enhance its accessibility, the partners launched an open-label, randomized Phase I clinical trial in September 2022 to evaluate the bioequivalence of a single subcutaneous dose (720 milligrams) of Leqembi compared to an equivalent dose delivered through intravenous injection.

Data from the subcutaneous study are anticipated in October 2023, and regulatory submissions for the maintenance dosing regimen and subcutaneous formulation are expected in the first quarter of 2024.

Currently, to receive treatment, “You have to drive to an infusion center and sit in a chair for a few hours,” Suvannavejh told BioSpace. He emphasized the strategic value of a treatment that could be administered under the skin at home by a caregiver and said this readout is important for Leqembi’s commercial success.

Huntington’s Disease

Wave Life Sciences’ WVE-003

WVE-003, developed by Wave Life Sciences, is an allele-selective oligonucleotide that attacks mutant proteins that produce the symptoms of Huntington’s disease (HD). It is designed to target the huntingtin (HTT) mRNA that carries a single nucleotide polymorphism that appears on the mutant HTT (mHTT) allele. By lowering the quantity of the mutant form of this protein, WVE-003 allows the wildtype (wtHTT) allele to function, preserving its beneficial effects in the central nervous system.

“HD is a tragic and unrelenting disease that passes through generations of families and has been compared to having ALS, Parkinson’s and Alzheimer’s all at once,” Paul Bolno, Wave’s president and CEO, told BioSpace by email. “Currently, there are no disease-modifying treatments for HD, so our primary goal is to develop a treatment that slows or stops progression of the disease.”

The Phase Ib/IIa SELECT-HD trial is evaluating WVE-003’s ability to reduce mutant HTT in the cerebrospinal fluid compared to a placebo. The study aims to optimize the dose level—30 mg, 60 mg or 90 mg—and frequency of WVE-003 administration to reach the desired early indicators.

"If WVE-003 is successful in the clinic, it has potential to be truly transformational,” Bolno said. Beyond treating symptomatic disease, he said Wave’s mHTT-lowering approach, which spares wtHTT, may also be beneficial in treating patients earlier, perhaps before symptoms of the disease present. “We are resolutely focused on what clinical success would mean to these families—and to future generations.”

Wave expects to deliver additional single-dose and available multi-dose biomarker and safety clinical data in the second half of 2023.

Amyotrophic Lateral Sclerosis

Seelos Therapeutics Inc.’s SLS-005

Developed by Seelos Therapeutics, SLS-005 (Trehalose) is being evaluated in the HEALEY ALS Platform Trial, a novel approach by which companies can conduct ALS clinical trials more efficiently.

“Currently, there are no treatments available that address the entire broad spectrum [of] patients with ALS,” Seelos Founder and CEO Raj Mehra told BioSpace in an email. “SLS-005, if successful in the HEALEY trial, would become the first drug to treat the broad ALS population based on a well-established and specific mechanism of action," he said. 

The registrational Phase II/III trial is examining the effectiveness of SLS-005 at stabilizing proteins and promoting autophagy in the brain to clear toxic protein aggregations characteristic of ALS. The results compare disease severity following a 90.5 mg/mL infusion of SLS-005 or a placebo for 24 weeks.

Seelos plans to release top-line data from the trial before the end of 2023. The company initiated an Expanded Access Program in April 2023 for ALS patients who are ineligible for the clinical trial.

“SLS-005 is not just one drug for one disease but one drug for multiple diseases,” Mehra said. The company is also evaluating SLS-005 in a late-phase registration-directed trial for SCA3 (or Machado-Joseph disease), an autosomal dominant cerebellar ataxia that occurs due to CAG repeat expansions in the ataxin protein. SLS-005 received the FDA’s Orphan Drug designation in 2020.

Multiple Sclerosis

Atara Biotherapeutics’ ATA188

Developed by Atara Biotherapeutics, ATA188 is a T-cell immunotherapy that targets Epstein-Barr virus (EBV)-infected B cells to treat nonactive secondary progressive multiple sclerosis (MS) and nonactive primary progressive MS.

Most treatment options for relapsing-remitting MS reduce flares but do not inhibit the worsening of disability in progressive forms of the disease. Current research supports the role that EBV plays in the development of MS. ATA188 is composed of T-cells obtained from healthy donors previously infected with EBV. The cells are primed to recognize and attack EBV proteins to potentially slow or halt disease progression.

Atara initiated the Phase I/II EMBOLD clinical trial in 2017 to determine the safety, tolerability and optimal dose of ATA188 and to evaluate its effect on clinical disability using the Expanded Disability Status Scale. The second half of the study evaluated the drug in participants with progressive forms of MS. Data from this phase, which will detail the drug’s ability to ease disease-related disability, is anticipated in November 2023.

Stacy Kish is a freelance science writer based in Pittsburgh, PA. Reach her at

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