Last month Marco Baptista – Vice President of Research Programs for The Michael J. Fox Foundation joined more than 9,000 people from pharmaceutical, biotechnology and investment firms for the annual J.P. Morgan Healthcare Conference to discuss progress and opportunities in biomedical research and care.
While there has always been a little Parkinson’s news shared at the conference, this year was different. The enthusiasm was palpable and the announcements on new results and programs kept coming. This momentum illustrates what we’re seeing across the Parkinson’s field: more therapies taking more steps toward the finish line.
Every treatment goes through three phases of testing (sometimes with multiple studies in one phase): Phase I tests safety in a small group of people, Phase II assesses safety and some efficacy measures in a larger group of people, and Phase III evaluates efficacy and safety in more people over a longer time. The Parkinson’s highlights from the conference include treatments marching through these phases of clinical testing.
We’re proud that our Foundation had a role in advancing many of these therapies, and we’ll continue to provide resources and tools to keep them moving.
Denali Announces Positive LRRK2 Trial Results
Denali Therapeutics has announced positive results from Phase I trials of its two LRRK2 inhibitors to slow or stop Parkinson’s disease. Mutations in the LRRK2 gene can cause Parkinson’s and lead to overactivity of the LRRK2 protein, which may contribute to cell loss. MJFF-funded research has found that Parkinson’s patients even without that genetic link can have greater LRRK2 activity, meaning therapies to lower that activity (like Denali’s) may help a broader patient population.
Our Foundation has helped advance LRRK2 therapies in varied ways. For example, a Foundation-led consortium proved it was safe to test this type of drugs in humans after initial findings threatened their continued development. And we’ve supported work to identify measures of LRRK2 activity (such as Rab proteins and the fatty acid BMP).
Denali just reported its trial of DNL201 in people with Parkinson’s (with and without a LRRK2 mutation) found that the drug did lower LRRK2 activity (as measured by a Rab protein and BMP). A lower dose was generally well tolerated, while a higher dose led to some effects such as headache, but all were manageable and reversible.
Denali’s other inhibitor, DNL151, was also safe and lowered LRRK2 activity in control volunteers. The company is now testing higher doses of DNL151 and will decide later this year which drug to move into a larger Phase II trial.
AFFiRiS Planning Phase II Alpha-synuclein Antibody Trial
Austrian biotech AFFiRiS said it intends to move its alpha-synuclein immunotherapy into Phase II trials. The protein alpha-synuclein clumps in cells of people with Parkinson’s, and the AFFiRiS treatment (called Affitope PD01A) triggers the body to produce alpha-synuclein antibodies, which may lower protein levels and protect cells.
PD01A was the first alpha-synuclein therapy to move into clinical trials, enabled by MJFF funding. A Foundation-supported Phase I trial found that the treatment was safe and tolerable and did seem to incite production of antibodies. We also supported studies that found additional doses of the therapy were safe and boosted alpha-synuclein antibody levels.
PD01A is now one of 11 therapies in clinical testing against alpha-synuclein for Parkinson’s disease.
Editor’s Note: On January 27 AFFiRiS announced it received input from the U.S. Food and Drug Administration on design of its Phase II trial, which it plans to start in the United States and Europe in the second half of 2020.
Inflazome Receives Drug Patent for Inflammation Drugs
The United States and Europe have granted Ireland’s Inflazome biotech company patents for compounds that inhibit the NLRP3 inflammasome. NLRP3 is a protein complex that initiates an inflammation response that could be harmful to cells. Inflazome is testing a drug (Inzomelid) against this target in control volunteers, and the patents may make the company’s portfolio more attractive to larger investors that can contribute funds and expertise for later-stage trials.
The Michael J. Fox Foundation funded pre-clinical work from the biotech’s founders to identify and develop this drug and is now supporting their testing of an NLRP3 imaging scan that would help evaluate the effect of Inzomelid and other NLRP3-targeting treatments.
Cerevel Announces Trial of Parkinson’s Symptom Therapy
Cerevel Therapeutics announced plans to start a series of Phase III trials evaluating its drug tavapadon for motor symptoms and fluctuations. Cerevel is a spin-off of Pfizer that acquired drugs for Parkinson’s and other diseases after the pharmaceutical giant closed its neurosciences program in 2018.
Tavapadon is designed to increase levels of the brain chemical dopamine, which is lost in Parkinson’s disease. The company plans to conduct four trials with different doses and length of follow-up.
Biogen Buys Drug to Treat Parkinson’s Sleep Problems
Another company also reported plans to test a drug bought from Pfizer. Biogen shared that it has acquired PF-05251749, a drug that could help regulate the body’s internal clock. The company plans to begin a Phase I trial later this year testing the compound in people with Parkinson’s and with irregular sleep wake rhythm disorder. This condition disrupts normal sleep so instead of an awake day and restful night, a patient may take multiple naps over a 24-hour period.
Biogen also plans to develop PF-05251749 for sundowning in Alzheimer’s, when people become more confused or agitated in the evening.
These are only a few of the many trials assessing new treatments for Parkinson’s disease. We recently held a webinar on ongoing trials to slow or stop Parkinson’s progression. Watch that anytime here.