FDA Grants Fast Track Designation for Longeveron’s Lomecel-B in Mild Alzheimer Disease

Wa’el Hashad

(Credit: Longeveron)

About a week after the FDA granted regenerative medicine advanced therapy (RMAT) designation to Longeveron’s Lomecel-B, the agency has granted the allogeneic cellular investigational therapy fast track designation for the treatment of mild Alzheimer disease (AD).¹ The granted designation was based on positive topline data reported from the phase 2a CLEAR MIND trial (NCT05233774), which will be presented at the 2024 Alzheimer’s Association International Conference, July 28 to August 1, in Philadelphia, Pennsylvania.

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.²

“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.¹

CLEAR MIND was a trial that comprised of 50 patients aged 60-85 years old with a diagnosis of mild AD in accordance with National Institutes of Health-Alzheimer’s Association criteria, a Mini-Mental State Exam (MMSE) score of 18-24, and a brain MRI and PET scan consistent with AD. In the trial, patients were randomly assigned 1:1:1:1 to either Lomecel-B at a dose of 25 x 106 cells (25M) on day 0, followed by placebo infusions at weeks 4, 8 and 12; Lomecel-B at a dose of 25M administered on day 0, week 4, week 8, and week 12 for a total of 4 doses; and at a dose of 100 x 106 cells (100M) administered on day 0, week 4, week 8, and week 12, for a total of 4 doses.

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In terms of efficacy, statistically significant improvements in the Composite Alzheimer’s Disease Score (CADS) were observed after 39 weeks in the Lomecel-B 25 x 106 cells (25M) x 1 dose (P = .091) vs placebo and for the pooled Lomecel-B groups (25M x 1 dose, 25M x 4 doses, 100 x 106 cells [100M] x 4 doses; P = .099). CAD combines the Alzheimer’s Disease Assessment Scale- Cognitive subscale 13, Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), Clinical Dementia Rating-Sum of Boxes, and left hippocampal volume. For the Lomecel-B 25M x 1 dose group, treated patients saw a statistically significant slowing of disease progression in left hippocampal volume (P = .015) relative to placebo.

Additional clinical data and imaging biomarker results, announced in 2023, further highlighted Lomecel-B’s impact on AD. All told, Lomecel-B™ (25M x 1 dose, P =0.009) and the pooled treatment group (25M x 1 dose, 25M x 4 doses, 100M x 4 doses, P =0.015) demonstrated statistically significant improvements in the Montreal Cognitive Assessment (MOCA), relative to placebo. In addition, investigators observed a dose-dependent response improvement in MMSE for Lomecel-B-treated patients (mean increase at highest dose: 3.0 [±3.6]; P = .028). Furthermore, quality of life, measured by the Alzheimer’s Disease Related Quality of Life scale, revealed higher level of improvement in patients on active therapy (100M x 4 doses).³

Supplementary data from CLEAR MIND also showed that Lomecel-B (100M x 4 doses) reduced whole brain volume loss by 49% (P = .034). Additionally, Lomecel-B™ (25M x 1 dose, P = 0.015) and the pooled treatment group (25M x 1 dose, 25M x 4 doses, 100M x 4 doses, P = 0.038) demonstrated statistically significant reductions in left hippocampal volume loss at Week 39 relative to placebo (25M x 1 dose degree of reduction: 84%). Lastly, brain volume preservation in the Lomecel-B (100M x 4 dose) dose group was accompanied by 20% and 33% reduction in left and right ventricular enlargement, respectively, at week 39 compared with placebo.⁴

“AD is a neurodegenerative disorder that leads to progressive memory loss and death, and its tremendous impact on our aging population is exacerbated by a lack of therapeutic options that slow disease progression or improve cognitive function,” Hashad said said in a statement.¹ “We believe that Lomecel-B, which demonstrated an overall slowing/prevention of disease worsening compared to placebo in the CLEAR MIND phase 2a clinical trial, has the potential to become an important treatment option for physicians and patients, and we look forward to sharing the latest data with the AD research and patient communities at AAIC 2024.”

REFERENCES
1. Longeveron® Announces U.S. FDA Grants Fast Track Designation for Lomecel-B™ for the Treatment of Mild Alzheimer’s Disease. News Release. Longeveron. Published July 17, 2024. Accessed July 18, 2024. https://investors.longeveron.com/news/News/news-details/2024/Longeveron-Announces-U.S.-FDA-Grants-Fast-Track-Designation-for-Lomecel-B-for-the-Treatment-of-Mild-Alzheimers-Disease/default.aspx
2. Longeveron announces positive top-line results for Lomecel-B in its CLEAR MIND phase 2a clinical trial in the treatment of mild Alzheimer’s disease. News release. Longeveron. October 5, 2023. Accessed July 18, 2024. https://investors.longeveron.com/news/News/news-details/2023/Longeveron-Announces-Positive-Top-Line-Results-for-Lomecel-B-in-its-CLEAR-MIND-Phase-2a-Clinical-Trial-in-the-Treatment-of-Mild-Alzheimers-Disease/default.aspx
3. Longeveron announces additional positive clinical data and imaging biomarker results from the CLEAR MIND phase 2a trial of Lomecel-B in the treatment of mild Alzheimer disease. December 20, 2023. Accessed July 18, 2024. https://investors.longeveron.com/news/News/news-details/2023/Longeveron-Announces-Additional-Positive-Clinical-Data-and-Imaging-Biomarker-Results-from-the-CLEAR-MIND-Phase-2a-Trial-of-Lomecel-Bin-the-Treatment-of-Mild-Alzheimers-Disease/default.aspx
4. Longeveron® Announces U.S. FDA Grants Lomecel-B™ Regenerative Medicine Advanced Therapy (RMAT) Designation for the Treatment of Mild Alzheimer’s Disease. News release. Longeveron. July 10, 2024. Accessed July 18, 2024. https://www.biospace.com/article/releases/longeveron-announces-u-s-fda-grants-lomecel-b-regenerative-medicine-advanced-therapy-rmat-designation-for-the-treatment-of-mild-alzheimer-s-disease/