The neuroscience drug development landscape in 2024 has been marked by both significant achievements and notable setbacks, reflecting the inherent challenges in treating complex neurological conditions. From novel schizophrenia treatments to Alzheimer's breakthroughs and ALS disappointments, the year has been a rollercoaster for researchers and patients alike.
Schizophrenia Treatment Advances and Setbacks
One of the year's highlights was the FDA approval of Bristol Myers Squibb’s Cobenfy (KarXT), the first new schizophrenia treatment in over three decades. This approval validated BMS's $14 billion acquisition of Karuna Therapeutics. Cobenfy targets both the M1 and M4 muscarinic receptors, showing promising Phase III results and securing FDA approval 35 years after the last novel drug for schizophrenia.
In contrast, AbbVie's emraclidine, a lead asset from their nearly $9 billion acquisition of Cerevel Therapeutics, failed to demonstrate efficacy in Phase II trials for schizophrenia. Emraclidine targets only the M4 receptor. Stifel analysts noted that the M1 receptor might contribute to cognitive efficacy, potentially explaining the difference in outcomes between Cobenfy and emraclidine.
Alzheimer's Disease: Approvals and Failures
The Alzheimer's space saw the approval of Eli Lilly’s donanemab (Kisunla), the third anti-amyloid antibody to reach the market in the past four years. This approval came as Eisai and Biogen discontinued Aduhelm to focus on Leqembi after securing its approval in 2023. However, the amyloid hypothesis continues to face scrutiny.
November was a challenging month for Alzheimer's research. Alector, in partnership with AbbVie, announced that AL002 failed to significantly slow clinical progression in Alzheimer’s patients, leading to a 17% workforce reduction. Simultaneously, Cassava Sciences revealed that simulfilam failed to meet pre-specified endpoints in a Phase III trial, amidst ongoing allegations of data manipulation.
ALS: High Hopes Dashed
Following the FDA approvals of Amylyx’s Relyvrio in 2022 and Biogen’s Qalsody in 2023, the ALS field experienced a setback when Amylyx announced that Relyvrio failed the Phase III PHOENIX trial. Despite an earlier Phase II trial showing a 10-month median survival extension compared to placebo, the company honored its commitment to withdraw the drug from the market, a move praised for its integrity.
Broader Neuroscience Landscape: Trials and Tribulations
Sage Therapeutics faced multiple failures, with dalzanemdor failing in Phase II trials for Parkinson’s, Alzheimer’s, and Huntington’s diseases, leading to its discontinuation. Sage's struggles began after receiving FDA approval for Zurzuvae in postpartum depression but not for major depressive disorder (MDD).
Relmada Therapeutics halted two Phase III trials of its MDD candidate REL-1017 after a futility analysis. Alto Neuroscience also reported that ALTO-100 failed to improve symptoms in a Phase II trial for depression. Amit Etkin, CEO of Alto, expressed disappointment, noting the significant unmet need, as 10% to 30% of MDD patients do not respond to typical antidepressants.
Rare Neurological Diseases: A Silver Lining
Rare neurological diseases saw positive developments. Orchard Therapeutics received approval for Lenmeldy, the first gene therapy for metachromatic leukodystrophy (MLD), in pediatric patients. Additionally, IntraBio’s Aqneursa and Zevra Therapeutics’ Miplyffa were approved for Niemann-Pick disease type C.
Sarepta Therapeutics’ Elevidys secured a label expansion for Duchenne muscular dystrophy (DMD) to treat patients at least 4 years old, regardless of their ability to walk, despite failing to meet the primary efficacy endpoint in its confirmatory trial.
Huntington's Disease: Emerging Hope
Despite setbacks, the Huntington’s disease space is gaining momentum, with Prilenia Therapeutics, Wave Life Sciences, and uniQure pursuing therapies targeting the disease's underlying causes. Novartis committed up to $2.9 billion in a deal with PTC Therapeutics for a Huntington’s drug, following a $1.3 billion deal with Voyager Therapeutics for gene therapies targeting neurodegenerative diseases.
