Last January, Avanir’s drug-device combo for the treatment of migraines, Onzetra Xsail, received FDA approval. 

The winds of change are blowing through the neurology market, attracting attention and investment from various — and at times unexpected — corners of the biopharma industry

Following a nearly decadelong sluggish period during which investment from big pharma dwindled considerably, a profound understanding of the biology behind neurological conditions is lending a refreshed air to drug development. Notably, scientists are knocking on the door of degenerative brain disorders, though sellable answers to their questions remain years away.

In the wake of diagnostic innovations and a spike in the understanding of genetic sequencing, drug developers have inched closer to discovering disease-modifying therapies for Alzheimer’s disease and other neurological conditions. New approaches bring with them the promises of early detection, personalized medicine, and disease modification.

See also: If Roche’s Ocrevus is approved, the already competitive MS market will gain another player

Trinity Partners’ senior partner Leslie Sandberg Orne attributes the renewed interest in CNS drug development to unmet need — and to the commercial potential that comes with it. And Will Reese, co-president and chief innovation officer at Cadient, identifies a trio of other motivating factors: emerging scientific approaches bearing new opportunities, the U.S. healthcare system demanding more efficacious and economically sound solutions, and an aging population driving the costs for care.

Lee Fraser, Digitas Health LifeBrands SVP and group director, says companies feel secure in their decision to forge ahead.

“Better scientific rationale and basic understanding of disease etiology can mitigate the traditional high risk and low reward in this category,” he explains.

But it’s not all about big pharma this time. Specialty companies, including Biogen, UCB, Sage Therapeutics, and Axovant Sciences, are all elbowing for a spot in the drug-development mix. “Much of big pharma has deprioritized CNS as development risks often exceed other therapeutic areas,” Sandberg Orne notes.


The neurology sector has also beefed up its brainpower, taking cues from the successes of other therapeutic categories — especially oncology and cardiology.

See also: The Michael J. Fox Foundation uses Facebook to recruit Ashkenazi Jews for Parkinson’s study

Along those lines, AbelsonTaylor VP and account director Eric Densmore believes the use of biomarkers to customize treatments will continue to surge. In addition to discovering biomarkers inside the human body, such as protein levels and axonal damage, companies are creating technologies to identify biomarkers outside the body. According to Densmore, examples include smartphone apps that can detect abnormalities in the gait of a patient with Parkinson’s disease.

Researchers are also upping their investment in gene-based treatments for CNS disorders. While gene therapy has been around for years, interest has surged primarily due to safer gene-delivery methods.

“Biology has become clearer in the past 10 to 15 years, giving us a better idea of when and how to intervene to slow the disease progression and, hopefully one day, prevent these conditions,” says Voyager Therapeutics CEO and president Steven Paul, MD. Voyager’s Phase Ib study is investigating VY-AADC01’s ability to replace aromatic L-amino acid decarboxylase (AADC), the enzyme lacking in the neurons of patients with Parkinson’s that converts levodopa into dopamine.

Entering a space on the heels of several gene-therapy failures, Voyager might have its work cut out for it. But Paul believes his company is barking up a different tree.

“We’re not trying to repair the brain or get neurons to grow back,” he explains. Rather, the methodology involves injecting viruses carrying the AADC gene into brain regions that don’t normally make dopamine.

Because scientists have yet to devise a drug that addresses the underlying cause of the age-related neurodegenerative disorder, approved Parkinson’s drugs such as Merck’s Sinemet (carbidopa and levodopa) and UCB’s Neupro (rotigotine) are meant to counteract the loss of dopamine-producing brain cells. Companies like Denali Therapeutics — which recently snagged an exclusive worldwide license to develop and sell Roche/Genentech’s leucine-rich repeat kinase 2 (LRRK2) inhibitors — are dreaming big on the Parkinson’s front. Cynapsus Therapeutics, acquired by Sunovion Pharmaceuticals for $624 million, recently claimed FDA fast-track status for Parkinson’s treatment APL-130277.


Two competing theories to explain the pathogenesis of Alzheimer’s disease — amyloid beta plaques and tau tangles — have driven pharma investment for years. Diagnostics progress is under way, Reese explains, especially in the development of new ways to visualize amyloid plaques to better MRI contrast agents.

Biogen’s aducanumab is attracting attention for its work in eliminating the amy­loid proteins responsible for damaging brain cells in patients with early-stage Alzheimer’s. The experimental drug, recently granted fast-track designation by the FDA, must overcome reports of fluid buildup and bleeding in the brain.

According to Sandberg Orne, the recent revelation that drugs can’t undo damage already inflicted on the brain has spurred new trial designs and positive results.

See also: Avanir marketing chief on selling first-in-class therapies

“We’re getting closer,” she says. “But the eventual approach to curing the disease will likely involve early intervention with a multi­pronged approach.”

So to that end, Eli Lilly/AstraZeneca’s oral BACE inhibitor AZD3293 has received fast-track status and Merck’s BACE inhibitor MK-8931 has entered Phase III trials. Lilly continues to explore other mechanisms for stamping out Alzheimer’s via solanezumab, which entered Phase III studies with a renewed approach following two trial flops.

Industry analysts believe the first drug developer to crack the challenging Alzheimer’s market will reap the rewards of commercial success — potentially billions of dollars in sales. Still, a long road lies ahead. In the meantime, market mainstays — Pfizer’s Aricept (donepezil), Allergan’s Namenda (memantine HCI), and Novartis’ Exelon (rivastigmine) — will continue to help patients manage symptoms.

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The $20 billion multiple sclerosis drug market is still in search of a treatment for primary pro­gressive MS. Many believe Roche’s ocrelizumab may be the drug to fill that gap.

Despite a few safety snags in 2015, Biogen handily leads the MS market with ­Tecfidera (dimethyl fumarate) for relapsing forms of MS. Some analysts expect its 2016 sales to grow 45.5% to $4.2 billion. Factor in the company’s blockbusters Tysabri (natalizumab) and Avonex (interferon beta-1a), and it’s easy to understand why Biogen has attracted more than its share of attention from would-be suitors.

One-third of the small sliver of neurology drugs gaining FDA approval in 2015 fell into the antipsychotic drug category, including Alkermes’ Aristada (aripiprazole lauroxil) for schiz–ophrenia and Vraylar (cariprazine) for schizophrenia and bipolar disorder. The market has grown crowded, mainly due to the revenue surge that often comes with the successful development of an antipsychotic.

See also: Biogen ends Tecfidera DTC campaign, citing prescriptions

Avanir Pharmaceuticals president and CEO Rohan Palekar has set his sights on growing the company into a major-league CNS player, an area he described to MM&M as the “widest open” of pharma sectors. Last January, Avanir’s drug-device combo for the treatment of migraines, Onzetra Xsail, received FDA approval. On its heels, the company’s AVP-786 is in Phase III trials for agitation in Alzheimer’s patients and Phase II trials for depression and schizophrenia.

Developed to constrict blood vessels and relieve swelling in the brain, triptans such as GlaxoSmithKline’s Imitrex (sumatriptan) and Merck’s Maxalt (rizatriptan) lead the acute migraine treatment market. Designed to interrupt a migraine already in progress, this class of drugs has attracted criticism for occasional ineffectiveness and side effects.

Meanwhile, antibodies that block a chemical in the nervous system, calcitonin gene-related peptides (CGRP), are making waves in migraine prevention. Studies show patient improvements as soon as three days after the injection of Teva Pharmaceuticals’ TEV-48125. Alder Therapeutics, Amgen, and Eli Lilly are also in the hunt. With continued trial success, these treatments are expected to launch in the next few years and may prove a boon for many.

As the science piece of CNS disorders becomes clearer, leaders will need to pivot to provide a more personalized approach to support. Data and analytics are quickly emerging as means to an end. “The more data a doctor has about a patient, the more customized the treatment,” Densmore says.


Innovations are on the horizon. In Parkinson’s and Huntington’s diseases, for example, small wearable adhesive sensors are being tested to collect data to measure patients’ responses to treatments.

“To find patients with a specific condition, data analytics techniques such as machine learning can identify patterns and characteristics that remain hidden when data are examined by human intervention,” says 81qd’s EVP of data analytics, Kelly Myers.

See also: Pharma companies turn to wearables to improve R&D

The sector’s struggle to identify patients has more far-reaching implications than just the individual’s health. The patient-selection process in neurological disease trials is complicated by poor diagnostic technique, according to Fraser.

“Objective measurement tools that correlate with clinical observation would be a big step forward in standardized patient inclusion and objective measurable outcomes,” he says.

Reese agrees that clinical-trial protocols are creating a need to differentiate through tech integration, innovative customer service, and experiences that connect patient and HCP in more personalized care. Progress in the neurological arena will require collaboration among researchers, biopharma companies, and tech experts to advance the treatment options for these devastating diseases.