Marina Necdina has more than 10 years of exerience as a bench scientist specializing in the areas of biochemistry, cell biology, and drug manufacturing.

Marina Necdina

Neuroscience is a complex market encompassing a variety of neurological conditions. Drug research and development in neuronal-related diseases has always been challenging. While the oncology sector made tremendous progress in the introduction of novel therapies, neuroscience lags behind in providing cures or even therapies to treat symptoms. The Alzheimer’s/dementia sector in particular represents a disappointing niche. The question is: did neuroscience become a holy grail for pharma or is real hope on the horizon?

Although the neuroscience drug market weighed in at more than $75 billion in 2019 with a prospect to reach $112 billion by 2027 (1), at closer look, it is less impressive. Overall, this market is divided into a number of sectors based on disorders: epilepsy, Parkinson’s, Alzheimer’s, cerebrovascular diseases, and others. Each of these sub-markets has its own challenges and progress.

The epilepsy sector saw FDA approval of Ztalmy (ganaxaqlone) from Marinus Pharmaceuticals (2) in 2021 and Parkinson’s has some potentially new therapeutics in development such as PR001 gene therapy from Prevail Therapeutics (acquired by Eli Lilly in 2021) (3). Yet overall, the neuroscience market has been a disappointment, especially when thinking about Alzheimer’s therapies.

For years, Biogen Idec was a known leader in the neuroscience space. Indeed, in June 2021 FDA granted accelerated approval to the controversial Aduhelm drug, developed by Biogen and Eisai (4). This monoclonal antibody targets aggregated forms of amyloid beta found in the brain of people with Alzheimer’s disease. Administration of Adulhem is expected to reduce a build-up of amyloid beta plaque, leading to neuronal death. However, clinical data was so unconvincing that even with accelerated approval, the drug was not accepted favorably within the scientific and clinical community leading to reduced sales, withdrawal of application to Europe market approval (5), and issues for coverage by Medicare (6). Consequently, Biogen needed to reduce its manufacturing capacity for Adulhem.

Despite setbacks, investments in neuroscience sectors continue. In 2021, Neumora Therapeutics raised $400 million in series A financing from more than a dozen venture capital firms plus $100 million from Amgen. The main goal is to develop precision small-molecule therapies for a multitude of brain diseases (7).

This is encouraging considering that Amgen axed its neuroscience program a while ago, but now revives it through partnerships (8). Moreover, the collaboration is based on Neumora’s precision neuroscience platform, a personalized approach similar to the recent trends in oncology.

Looking among Big Pharma companies, one can say that Biogen is still in the leading position in the neuroscience sector. In June 2022, it invested more than $700 million on Alectos’ preclinical oral Parkinson’s disease candidate AL01811 (9). The drug is a GBA2 inhibitor that corrects acid levels in lysosomes, linked to the development of neurodegenerative diseases.

Analysis of clinical trials for Alzheimer’s (10) indicates that most of the candidates in clinical trials are monoclonal antibodies or small molecule. At the same time, novel approaches such as stem or cell therapies to treat dementia, are coming mostly from academia or small biotech pipelines. Aspen Neuroscience is an example of a company working on autologous stem cell-based therapy for Parkinson’s disease.

Neurona Therapeutics develops off-the-shelf, allogeneic neuronal, glial, and gene-edited neural cell therapies for single-dose targeted repair of the nervous system (11). Furthermore, it has in house facilities for current good manufacturing practice (CGMP) manufacturing.

Despite its controversy, approval of Biogen’s Aduhelm in 2021 helped to put the neuroscience sector in the spotlight again.

Indeed, in 2021 Eli Lilly decided to split one of its divisions that develops and markets drugs for neurology and inflammatory diseases (12). Lilly believes that this move may help to shorten path to market for the company’s experimental Alzheimer’s treatment donanemab (13).

Like Aduhelm, donanemab is also an anti-amyloid beta monoclonal antibody, yet Lilly hopes to best its rival and thus gain greater market share reaching potentially $6 billion in sales by 2026.

A new, or renewed, market entry in the Alzheimer’s sector is gantenerumab, developed by Roche (14). This antibody is expected to bring around $2.5 billion by 2026. Roche believes that the introduction of this drug may expand its activities beyond its oncology staples and move more deeply into central nervous system disorders.

Overall, even with disappointing Aduhelm sales and its problematic insurance coverage, it had a positive effect on neuroscience market. It revived interest and desire of both pharma and biotech to research and invest further in such a challenging area.

More importantly, it brought to attention the fact that this market needs different research and therapeutic approaches, such as stem and cell therapies.

And while new trends in neuronal therapy development is encouraging, it also means other types of challenges, not only in R&D but also from a manufacturing perspective. In particular, one should remember that cell therapies may have much more lot-to-lot variations and can be dependent on more factors to regulate and smooth the path for commercial production.

The neuroscience market struggles to elevate from quasi stagnation. Despite research efforts, no breakthrough therapies were offered to the patients. Thus, the question industry needs to ask if current approach is indeed “winning”. Alzheimer’s sector is the best example to analyze. Although p-tau and amyloid plaques are known hallmarks of the disease, current therapy using anti-plaque approach might not be the best option to tackle these diseases.

In addition, there is undeniable, strong need for better research models and proper diagnostics. Potentially, better biomarkers and companion diagnostics development for Alzheimer’s and other neuro conditions will be a winning attitude.

Moreover, industry should utilize its expanding experience with cell therapies in oncology to apply its development and manufacturing methods to neuronal cell therapies. It is obvious, a shake-up in methodology, diagnostics and overall attitude toward neuroscience is needed to find these long awaiting cures for such debilitating conditions.

Market Research, Neurological Disorder Drugs Market. Global Industry Analysis, Size, Share, Growth, Trends, and Forecast, 2019-2027

2. PharmTech Editors, “Marinus Pharmaceuticals Announces FDA Approval of ZTALMY for CDKL5 Deficiency Disorder,” 

3. Alzforum, Databases for therapeutics, 

FDA Grants Accelerated Approval for Alzheimer’s Drug

5. Biogen, “Update on Regulatory Submission for Aducanumab in the European Union,” Press Release, April 22, 2022.

6. J. Wechler, “Medicare Limits Aduhelm Coverage to Patients in Clinical Trials,” 

7. Businesswire, “Neumora Therapeutics Launches to Pioneer a New Era of Precision Medicines for Brain Diseases,” Businesswire.com, Press Release, Oct. 7, 2021.

8. Amgen, “Amgen and Neumora Therapeutics Announce Strategic R&D Collaboration to Accelerate Novel Precision Therapies for Brain Diseases,” Press Release, Oct. 7, 2021.

9. Alectos Therapeutics, “Biogen and Alectos Therapeutics Announce License and Collaboration Agreement for AL01811, a Novel GBA2 Inhibitor for the Potential Treatment of Parkinson’s Disease,” Press Release, June 6, 2022.

10. J. Cummings, “Alzheimer’s Disease Drug Development Pipeline: 2022,” 

12. T. Garcia, “Eli Lilly Creates Neuroscience and Immunology Business Units,” 

13. M.A. Mintun, “Donanemab in Early Alzheimer’s Disease,” 

14. D. Garde, “Awaiting ‘Definitive’ Alzheimer’s Drug Data, Roche and Genentech Launch Ambitious New Study,” 

When referring to this article, please cite it as M. Necdina, “What is Wrong with the Neuroscience Drug Market?,” 

Articles

Pharma should expand on successful cell therapies in oncology by applying these development and manufacturing methods to neuronal cell therapies.