Donanemab-AZBT

Neurology has long been seen as a high-risk investment. Biopharma’s understanding of how the brain works is still rudimentary compared with that of other organs, as is its knowledge of what drives specific neurological diseases. Patient populations are also heterogeneous, so success in early- or mid-stage trials doesn’t necessarily translate into wins later in the clinic. But the area now seems “ripe” for dealmaking, according to a majority of observers interviewed by Endpoints News . There’s already been a handful of large deals this year, starting with Johnson & Johnson’s $14.6 billion buyout of Intra-Cellular Therapies and its bipolar disorder drug Caplyta. Eli Lilly followed suit in May with its acquisition of non-opioid pain biotech SiteOne Therapeutics for up to $1 billion . Sanofi also snapped up Alzheimer’s drugmaker Vigil Neuroscience for $470 million the same month. And there’s a lot more interest in neurology than the volume of publicly-announced deals suggests, said Greg Benning, partner at Back Bay Life Science Advisors. The number of deals is likely to increase as several large drugmakers approach a patent cliff, added Frances Stocks Allen, partner at the law firm Cooley. The perceived risk on the acquirer side has “come down a bit” because companies now have more ways to gauge the likelihood of success of a neurology program, like looking at biomarkers and patient stratification approaches, Benning said. And on the regulatory side, the FDA is starting to signal a more flexible attitude to approving neurology drugs, Stocks Allen added. It’s also easier to identify where drugs are needed in neurology, compared with areas like oncology, which tend to have more complex treatment paradigms, said Ali Pashazadeh, founder at Treehill Partners. For instance, there are still no approved disease-modifying treatments for several neurodegenerative diseases, said Laurence Barker, a partner at SV Health Investors focused on the Dementia Discovery Fund. But Pashazadeh was skeptical about a potential rise in neurology dealmaking. He noted that many large drugmakers still want to target companies that are beyond the human proof-of-principle stage. It’s not that pharma companies have more of an appetite for neurology deals, but rather that biotechs are finding new ways of generating capital and are developing drugs at a lower cost, which means they’re more likely to meet pharma’s deal thresholds, he added. Still, Arrowhead Pharmaceuticals CEO Christopher Anzalone said “there’s no big pharma on the planet that can afford not to be in this space if things start to work out.” Earlier this year, Arrowhead’s preclinical RNAi Parkinson’s program grabbed the attention of Novartis, which bet $200 million upfront and up to $2 billion in milestones. Buzzy approvals and launches in neurology are one element that’s raised confidence in dealmaking, according to Barker. Breakthroughs in the past few years include the FDA approval of anti-amyloid antibodies for Alzheimer’s, a notoriously challenging disease. The agency greenlit Eisai and Biogen’s Leqembi under an accelerated pathway in 2023. And Eli Lilly’s Kisunla is the latest to join the market, having secured a full approval in early 2024. While these first-generation drugs have shown “modest benefit,” Barker noted that “success breeds success.” In the first quarter of the fiscal year, Leqembi made about $151 million , with GlobalData analysts projecting it could hit $12.9 billion in cumulative sales by 2028. Kisunla sales reached $49 million in the second quarter, with Wall Street consensus suggesting it could make $5 billion a year at its peak. But initial uptake of both drugs has been slower than anticipated. The FDA’s decision to okay Leqembi was initially met with skepticism by some onlookers who were concerned about the rate of brain swelling and bleeding events at the time, though confidence in the drug’s safety profile has since buoyed a little. Another factor that’s de-risked neurology deals is the adoption of biomarker-based approaches to R&D. Biomarkers serve as indicators of efficacy, easing the bar companies have to meet to get a drug past the finish line, Stocks Allen said. “We don’t have to go to clinical outcomes to see if a compound works,” said Erik Wallström, therapeutic area head, neurology development, Sanofi R&D. That’s been a “complete game-changer” in terms of driving interest from onlookers, he added. Sanofi’s acquisition of Vigil centered on the biotech’s Alzheimer’s drug candidate, called VG-3927, which targets a protein known as TREM2 that’s expressed by the brain’s immune cells. The soluble form of TREM2 can be detected in spinal fluid and blood, serving as a biomarker for immune response in the brain. But research on TREM2 is still quite limited compared with better-known biomarkers such as levels of amyloid plaque in the brain. Several other candidates targeting TREM2 for Alzheimer’s have disappointed in the clinic, including those advanced by Alector and Denali Therapeutics . Leqembi was approved based on its ability to reduce amyloid plaques in the brain, which are believed to correlate with cognitive decline in Alzheimer’s. But strong biomarker results don’t always translate to clinical outcomes. Eisai and Biogen’s older anti-amyloid antibody, Aduhelm, was approved in 2021 based on biomarker data, but was later pulled from the market after confirmatory results failed to show a clear improvement in cognitive decline. Elsewhere, neurofilament light chain (NfL) in the context of amyotrophic lateral sclerosis (ALS) is “increasingly being recognized as a very strong surrogate endpoint,” Barker said. NfL is a protein that helps nerve cells maintain their structure and stability, and is released when the cells are damaged. The extent to which NfL levels correlate with clinical decline is still unclear. Still, in April 2023, Biogen’s antisense oligonucleotide drug Qalsody clinched accelerated approval for ALS patients with a mutation in the SOD1 gene based on its ability to cut levels of NfL in the blood. Qalsody is being tested in a confirmatory Phase 3 trial called ATLAS, which is looking at whether the drug can prevent the disease from manifesting clinically in presymptomatic patients. SOD1 mutations affect just 2% of ALS patients worldwide, according to Biogen. This means the potential market in the US consists of just 300 to 400 people. Biogen has said it doesn’t expect to make a profit from Qalsody. Other drugmakers have successfully leveraged biomarkers in spaces other than neurodegeneration, including rare pediatric conditions. In 2023, Sarepta clinched FDA accelerated approval for its gene therapy Elevydis to treat ambulatory boys with Duchenne muscular dystrophy (DMD). That was converted to full approval in 2024 after a confirmatory study showed significant improvements across all functional secondary endpoints, despite a miss on the primary endpoint of the North Star Ambulatory Assessment. But Elevydis has been mired in controversy, with a small number of patient deaths prompting the FDA to order a pause in shipments in the summer, although it later reversed its decision. That wasn’t the first time the FDA walked back on its decisions regarding Sarepta. In December 2019, the agency greenlit Sarepta’s Vyondys 53 for a subset of DMD patients, after rejecting the drug just four months prior. In tandem with the advancement of biomarkers in R&D, there have been some strides in biomarker-based diagnostic tests in neurology, Barker said. These tests make it quicker and easier to diagnose and track the progression of certain diseases, which further de-risks neurology drug development and associated deals, he added. In May, the FDA cleared the first test to diagnose Alzheimer’s based on levels of tau and amyloid protein in the blood. Fujirebio Diagnostics’ Lumipulse is intended for use in adult patients aged 55 and older who are showing signs and symptoms of the disease, including cognitive decline. The test could help reduce the need for expensive PET scans or invasive spinal taps. This month, Roche and Eli Lilly said their tau-based Alzheimer’s test was greenlit for use in a primary care setting in the same type of patients. But many biomarker-based diagnostics are still in the early stages of development and demonstrate varying levels of accuracy. Developers often struggle to achieve the right levels of sensitivity and specificity for their assays, as well as reproducibility of results. Even so, the uptick in biomarker-based strategies shows that neuroscience is starting to learn from fields like oncology, which have wielded precision medicine to their advantage. Precision medicine involves targeting subgroups within a broader patient population who share the same underlying biology, such as the same genetic driver of a disease, Barker explained. The broader adoption of AI and machine learning technologies, early as they may be, means it’s also becoming faster to identify which neurology candidates are likely to succeed, Citeline analyst Emma Wille told Endpoints in an email. For instance, Dallas-based Lantern Pharma has developed an AI-powered platform that helps predict how well small molecules can penetrate the blood-brain barrier. With all these factors coming together, neurology is “ripe with opportunities for success,” Wille said. “Yes, there’s risk and uncertainty in this therapeutic area — but the payoff could be substantial.”

Virtual memory clinic Isaac Health announced Wednesday that it has partnered with Eli Lilly's direct-to-consumer platform, LillyDirect, to expand access to its Alzheimer's disease services. The collaboration is expected to boost Isaac Health's visibility and help the company reach more patients amid rising demand for dementia care. According to the company, over 7 million Americans are living with Alzheimer's disease, yet timely diagnosis and treatment remain difficult to access.'Dementia care desert'"Half the country is in a dementia care desert," said Joel Salinas, chief medical officer at Isaac Health. "The window of time where treatments can actually make a positive impact is very limited, while the average wait time for specialists in this field is approximately a year or more." In contrast, Isaac Health connects patients with dementia specialists in about two weeks, CEO and co-founder Julius Bruch told FirstWord. "[This allows] for timely care for a condition where time is of the essence for prolonged independence and cognitive health," he said.Isaac Health provides comprehensive evaluation and treatment through a virtual platform staffed by board-certified neurologists, psychologists and other dementia experts. Its services include cognitive and neuropsychological testing, neurological exams, brain imaging, bloodwork and spinal fluid analysis. Access to disease-modifying drugsPatients can access a range of medication treatments, including disease-modifying therapies such as Eisai and Biogen's Leqembi (lecanemab) and Eli Lilly's Kisunla (donanemab). Non-pharmacological options like cognitive therapy from speech-language pathologists are also available."Disease-modifying treatments have represented a seismic shift in the way we approach Alzheimer's disease — but they are only safe and effective if patients are diagnosed early and receive the right ongoing care," Salinas noted.The platform also offers long-term care coordination, including medication monitoring, early identification of medical concerns and referrals to community and social support services. Caregivers have access to training, coaching, round-the-clock support and respite services.  According to Bruch, data from an independent evaluation showed that 73% of patients reported improved neurocognitive symptoms after six months, and 92% reported progress toward cognitive goals. The programme also resulted in a 38% reduction in emergency department visits and a 28% reduction in hospital days, he said.In August, Isaac raised $10.5 million to support its expansion and is now available in all 50 US states. LillyDirect, launched in January 2024, initially focused on improving access to popular weight loss medications and has since partnered with Amazon, Ro, Teladoc and LifeMD to prescribe ELi Lilly's Zepbound (tirzepatide). In March, the platform expanded into Alzheimer's care, first directing patients to Synapticure for teleneurology services.