Anyone whose life has been touched by Parkinson’s disease knows the importance of awareness and the development of more effective treatments. Every six minutes, someone in the U.S. is diagnosed with Parkinson’s.
However, one of the most poignant facts pertaining to Parkinson’s treatment is that there has been virtually no progress in treating it over the last 50 years. In honor of Parkinson’s Disease Awareness Month in April, I’m highlighting four publicly traded biotech companies working on potentially life-altering treatments for Parkinson’s.
The current standard of care for Parkinson’s
A patient develops Parkinson’s disease when their brain stops making enough dopamine or when too many dopaminergic neurons die, resulting in many nerve-related symptoms, including the tremors that are the hallmark symptom of this illness. Dopamine is the chemical messenger responsible for transmitting messages between the nerves that control muscle movements and those related to the brain’s reward and pleasure centers.
Over the last 60 years, the standard of care for Parkinson’s treatment has been levodopa, a drug that helps replace the depleted dopamine. However, while it was a wonder drug when it was introduced, levodopa has several shortcomings.
For example, it can cause levodopa-induced dyskinesia (LID), a type of tremor that occurs when the drug is used for too long or at too high of a dose. Additionally, levodopa doesn’t help much with the non-movement Parkinson’s symptoms, like speech and swallowing problems, dementia, problems with cognition, and sleep issues.
Finally, the drug typically lasts only about four hours, so it wears off overnight while the patient sleeps. As a result, many patients wake up with rigid muscles and have problems getting out of bed in the morning, a condition referred to as the “off state” because their Parkinson’s symptoms are not under control.
One other drug commonly used in Parkinson’s treatment is carbidopa. Carbidopa limits the unwanted side effects levodopa causes on organs outside the central nervous system by focusing levodopa distribution into the brain and central nervous system.
These outcomes are the targets for new and upcoming treatments
One of the primary goals of Parkinson’s treatment is extending the length of a patient’s “on state,” which means their motor symptoms are optimally controlled. The overarching goal is to improve the patient’s quality of life. The gold standard for outcomes may include reducing tremors and managing the patient’s bradykinesia, which is slowed movements that make it difficult for the patient to move at all.
Other targeted outcomes include improving rigidity and balance and non-movement-related symptoms. These other symptoms can include fatigue, constipation, urinary problems, sleep issues, pain, mood and cognitive changes, hallucinations, delusions or paranoia, impulsiveness, and vision, dental, and skin problems. Finally, because levodopa often causes so many side effects, another goal of Parkinson’s treatment is to minimize the side effects of treatment.
While the last 50 years have been unfruitful for Parkinson’s research, the next 10 to 20 years promise to be exciting as new treatments that significantly improve patient’s quality of life are introduced. Here are five biotech firms with interesting drug candidates for Parkinson’s currently in clinical trials.
Anavex Life Sciences
Anavex Life Sciences (AVXL) is developing blarcamesine, which targets Parkinson’s disease dementia. The drug candidate aims to improve behavior and normalize biochemical changes by increasing sigma-1 receptor expression, preventing toxic mRNA from being translated into proteins. The sigma-1 receptor is a protein related to neuroinflammation and tasked with brain functions like memory, while mRNA is genetic material that tells the body how to make proteins.
Anavex released an update on its Phase 2 clinical trial for Parkinson’s disease dementia at the end of March. A 48-week open-label extension clinical trial on blarcamesine demonstrated consistent longitudinal improvement in patients’ clinical symptoms for the first time. A previous double-blind Phase 2 trial revealed an 18.9% improvement in non-motor and motor symptoms over 14 weeks.
Separately, a small clinical trial funded by the Michael J. Fox Foundation for Parkinson’s Research found that blarcamesine significantly improved cognitive function, memory, and REM sleep in patients with Parkinson’s disease dementia.
Annovis Bio (ANVS) is developing buntanetap, which is designed to target multiple neurotoxic proteins implicated in neurodegenerative diseases. Reducing the levels of those proteins also reduces the inflammation causing the Parkinson’s symptoms.
In July 2022, the FDA authorized the company to move forward with its Phase 3 clinical trial in early Parkinson’s. The Phase 3 trial aims to measure buntanetap’s effectiveness in improving patients’ motor functions and ability to perform daily living activities.
In a Phase 2a trial, buntanetap was found to provide a statistically significant improvement in motor functions in Parkinson’s patients. Annovis Bio expects to have an interim data analysis from its Phase 3 trial of buntanetap sometime around mid-2023.
BioVie (BIVI) is testing NE3107, which also aims to improve Parkinson’s symptoms by reducing inflammation. (Disclosure: BioVie is a client of Quantum Media, LLC; the author is the CEO of Quantum Media Group.) NE3107 targets TNF-α, the master regulator of inflammation, to halt the inflammatory cascade that leads to a feedback loop triggering even more inflammation in the brains of Parkinson’s patients, causing the disease to progress.
Research funded by the Michael J. Fox Foundation showed that NE3107 was equally effective as levodopa in non-human primates and that the combination of NE3107 and levodopa provided the most motor control.
In March, BioVie presented the latest results from its Phase 2 trial combining NE3107 with levodopa at the International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders (AD/PD 2023). Those results build on the topline data released in December.
The company said patients receiving the combination saw clinically meaningful improvements in their motor-related symptoms compared to those taking only levodopa. BioVie also reported that significantly more patients treated with NE3107 were assessed as being in the “on state” in the morning after their usual Parkinson’s medications had been withheld for at least eight hours, compared to those taking the standard of care alone with placebo.
Given the unexpected and significant “morning-on” findings, the company is initiating a Phase 2b/3 trial of NE3107 as a monotherapy for treatment-naive Parkinson’s patients (those who haven’t yet been treated for the disease). This group represents a large unmet medical need and could lead to the first new therapy for Parkinson’s since the introduction of levodopa.
Denali Therapeutics and Biogen
Denali Therapeutics (DNLI) and Biogen (BIIB) have teamed up to develop DNL151/BIIB122, which aims to counter Parkinson’s symptoms by blocking the leucine-rich repeat kinase 2 (LRRK2). DNL151 is aimed at patients with certain gene mutations. Denali’s other LRRK2 inhibitor, DNL201, will serve as a backup to DNL151. Development of DNL201 was halted in 2020.
The LRRK2 gene tells the body how to make the protein dardarin. The leucine-rich region of the dardarin protein holds a significant amount of the protein-building block leucine. LRRK2 also regulates responses in the brain’s immune cells, triggering neuroinflammation in Parkinson’s patients and resulting in symptoms of the disease.
DNL151 was pushed into late-stage clinical trials in August 2020. Denali and Biogen began a Phase 2b trial in early-stage Parkinson’s that’s due to be completed in August 2025. They have also started recruiting for a Phase 3 clinical trial of 400 patients with early-stage Parkinson’s and certain mutations in the LRRK2 gene. LRRK2 mutations are one of the most common genetic causes of the disease. This trial is scheduled to be completed in January 2031.
As of January 2023, Denali Therapeutics and Biogen had not published any preclinical data on DNL151/BIIB122 yet.
Investing in clinical-stage Parkinson’s treatments
Parkinson’s is the second-most-common neurodegenerative disease after Alzheimer’s. Thus, the lack of progress in treating it over the last 50+ years presents a compelling opportunity for the biotech companies that can get successful treatments over the finish line.
The global Parkinson’s disease treatment market was valued at $4.28 billion in 2021 and is expected to see a compound annual growth rate of 12.1% between 2022 and 2030. The Parkinson’s treatments under development by the four above biotech companies offer a bit of hope for patients and families affected by this disease.