From the FDA approval of Bristol Myers Squibb’s Cobenfy as the primary new schizophrenia remedy in additional than three many years to the failure of Sage Therapeutics’ dalzanemdor in three neurodegenerative illnesses, it has been a 12 months of candy triumph and crushing disappointment for neuroscience drug builders—largely reflecting the fact of those confounding circumstances.
Maybe it’s simply my fascination with neuro—which regardless of (or possibly due to) its challenges, has lengthy captured my consideration—however I imagine a few of 2024’s most compelling storylines have come from this house. There was the battle between BMS’ and AbbVie’s multibillion greenback neuro acquisitions from final December—Karuna vs. Cerevel within the schizophrenia house—which resulted in spectacularly totally different outcomes. After which there was the approval of Eli Lilly’s donanemab (Kisunla), the primary anti-amyloid competitor in Alzheimer’s for Eisai and Biogen, which discontinued Aduhelm this January after securing Leqembi’s approval in 2023. Now, Kisunla and Leqembi are rolling out because the amyloid speculation nonetheless faces doubt.
Given the character of neurological illnesses and biopharma’s myriad bids to resolve them, these cleaning soap opera storylines are to be anticipated, and even inspired, because it cumulatively means extra progress for intractable, usually deadly, illnesses.
Schizophrenia
One of many highest highs this 12 months was the FDA’s late September approval of Cobenfy, which served as indeniable validation for BMS’ $14 billion acquisition of Karuna. Lower than two months later, nevertheless, AbbVie’s emraclidine—a lead asset within the pharma’s practically $9 billion buyout of Cerevel—failed to indicate efficacy in two registration-style Section II trials for schizophrenia.
Two parallels are noteworthy right here. The primary, after all, pertains to the enterprise technique, with each pharma corporations scooping up the belongings in multibillion greenback acquisitions in the identical month. Cobenfy proved its value with promising Section III outcomes in April and secured FDA approval in late September—35 years to the day after the final novel drug was authorized for schizophrenia.
The second likeness between Cobenfy and emraclidine is the science that underlies them: each medicine belong to the muscarinic class. Muscarinic receptors play a job within the pathology of schizophrenia, and the house has caught hearth of late with a number of corporations creating therapeutic candidates. Cobenfy’s approval portended success for the drug class, and AbbVie appeared shut on BMS’ heels with emraclidine.
However there’s a distinction between the 2 belongings: Cobenfy targets each the M1 and M4 receptors, whereas emraclidine solely targets M4. “There’s been a longstanding thesis that M1 might contribute to efficacy on cognition,” Stifel analysts famous. The way in which these two belongings carried out, it actually looks like that might be the case.
Alzheimer’s and ALS
Schizophrenia might have stolen the present within the latter a part of 2024, however we should not overlook that early within the second half, Alzheimer’s researchers and sufferers celebrated the approval of Kisunla—the third anti-amyloid antibody to hit the market prior to now 4 years. However as is sort of at all times the case in Alzheimer’s, there have been additionally a number of failures.
November was a very dangerous month for the house—and once more, for AbbVie. On Nov. 25, Alector introduced that its AbbVie-partnered investigational antibody AL002 didn’t considerably sluggish scientific development in sufferers with Alzheimer’s illness. The flop triggered a layoff of roughly 17% of the biotech’s workforce. The identical day, Cassava Sciences revealed that its controversial Alzheimer’s candidate simulfilam failed to fulfill all pre-specified co-primary, secondary and exploratory biomarker endpoints in a Section III trial. The consequence follows allegations of “information manipulation” associated to the drug.
In amyotrophic lateral sclerosis (ALS), in the meantime, the FDA approvals of Amylyx’s Relyvrio in 2022 and Biogen’s Qalsody in 2023 generated momentum, however not three months into 2024, Amylyx introduced that Relyvrio failed the Section III PHOENIX trial. The drug was authorized primarily based on outcomes from the Section II CENTAUR trial, during which it prolonged median survival by greater than 10 months in contrast with placebo. Discuss a rollercoaster trip for Amylyx co-CEOs Josh Cohen and Justin Klee. To their credit score, the duo had vowed to drag the drug from the market if PHOENIX was not profitable, and in April they made good on this promise. This, in itself, will get my vote for one among 2024’s prime tales.
“Given the excessive unmet medical want that also exists in psychological sickness and devastating illnesses like Alzheimer’s illness and ALS, we’ll proceed to look to business to give you nice innovation in relation to new mechanisms of motion, therapeutic modalities and approaches, in addition to use of novel endpoints and novel scientific trial design,” Graig Suvannevejh, senior biopharmaceuticals and biotechnology fairness analysis analyst at Mizuho Americas, instructed BioSpace in an e-mail.
Broader Neuro House
Trying extra broadly throughout the business, there are loads extra examples of the trials and tribulations that plague this space of drug growth. Sage Therapeutics, for instance, has been using one of many park’s darker rollercoasters. The biotech’s shares have misplaced greater than 90% of their worth over the previous 12 months and a half, thanks largely to a hat trick of mid-stage flops. In April, dalzanemdor failed to indicate efficacy in opposition to Parkinson’s illness; it then failed in Alzheimer’s and Huntington’s—the ultimate blow that prompted the corporate to discontinue the asset’s growth.
Sage’s downward spiral started in August 2023 when it—together with companion Biogen—gained FDA approval for Zurzuvae in postpartum despair (PPD) however didn’t safe the regulator’s nod for main depressive dysfunction (MDD), a a lot bigger indication that has had its justifiable share of misses recently. Earlier this month, Relmada Therapeutics halted two Section III trials of its MDD candidate REL-1017 after a futility evaluation, main the corporate to think about “strategic options.” And in October, Alto Neuroscience reported {that a} trial of ALTO-100 failed to enhance signs in a Section II trial.
“We’re disheartened by the outcomes from this research because the unmet want on this affected person inhabitants is immense,” Alto CEO Amit Etkin mentioned in a assertion on the time. Certainly, between 10% and 30% of MDD sufferers don’t reply to typical antidepressant remedies.
On a excessive observe, uncommon, neurological illnesses loved a second in 2024. In March, Orchard Therapeutics gained approval for Lenmeldy, the primary gene remedy for metachromatic leukodystrophy (MLD), a uncommon and heritable metabolic illness that may trigger organ injury and neurological points, in pediatric sufferers. Then, in September, sufferers with Niemann-Decide illness kind C noticed the approval of the primary remedies for the ultra-rare and progressive neurodegenerative illness because the FDA greenlit IntraBio’s Aqneursa simply days after Zevra Therapeutics’ Miplyffa. Yet one more uncommon illness that scored a victory this 12 months is Duchenne muscular dystrophy (DMD), with Sarepta Therapeutics’ Elevidys securing a label enlargement to deal with sufferers who’re a minimum of 4 years previous, regardless of whether or not they can stroll. This was regardless of the gene remedy’s failiure to fulfill the first efficacy endpoint in its confirmatory trial.
Lastly, regardless of Sage’s current failure, the Huntington’s house is starting to see some actual traction. Prilenia Therapeutics, Wave Life Sciences and uniQure are all eyeing paths to approval of therapies that might tackle the illness’s underlying trigger. Funding is ticking up as effectively. This 12 months, Novartis dedicated as much as $2.9 billion in a cope with PTC Therapeutics for a Huntington’s drug, simply months after inking an as much as $1.3 billion deal with Voyager Therapeutics to develop gene therapies for the illness and spinal muscular atrophy.
Taken collectively, I’d say the rollercoaster that’s neuro produced extra thrills than bumps in 2024—however the twists and turns are a stark reminder of simply what a black field the mind is. Therapies for these illnesses are really the holy grail of biopharma, and as at all times, we’re shifting incrementally nearer to solutions.
