Parkinson’s disease is a complex, progressive neurological disorder affecting up to 10 million people worldwide.
Probably caused by clumps of alpha-synuclein protein that damage dopamine-producing cells governing motor control, Parkinson’s is characterized by tremor, rigidity, poor posture and slow movement.
About 150 Israeli startups are developing technologies to help prevent, stop or even cure Parkinson’s. Azilect (rasagiline), one of the most successful drugs for managing Parkinson’s symptoms, was developed in Israel by Prof. Moussa Youdim and is manufactured by Teva Pharmaceuticals.
Former Teva executives formed Pharma Two B in 2007 to see whether combining rasagiline with another approved Parkinson’s drug, pramipexole, could manage symptoms of early Parkinson’s in a better and safer way than either drug alone.
The seven-employee company’s lead investigational product candidate, P2B001, has completed successfully both Phase IIb and Phase III studies investigating its efficacy and safety as a once-daily oral treatment for early-stage Parkinson’s disease.
A new drug application (NDA) is expected to be submitted to the US Food and Drug Administration in 2024.
Best of both drugs
“The holy grail in Parkinson’s is to find something that stops the disease’s progression, but nothing has advanced significantly yet, so we are left with controlling symptoms,” explains Dan Teleman, CEO of Pharma Two B.
“We’re targeting early Parkinson’s, the first few years after diagnosis before the disease progresses,” he tells ISRAEL21c.
In the later stages, many patients develop complications that necessitate taking levodopa, one of a class of drugs called central nervous system agents.
“For early Parkinson’s, physicians have been using several classes of drugs over the years. The most effective class is dopamine agonists, which mimic the binding of dopamine to its receptor. The best-known dopamine agonist is pramipexole.”
But there’s a catch. While pramipexole is very effective at controlling symptoms, it can cause negative side effects such as daytime sleepiness, nausea, vomiting, and even impulse control disorder.
To avoid these side effects, physicians prefer using other classes of drugs such as MAO-B inhibitors, the family that rasagiline belongs to.
Teleman says that rasagiline “is kind of the opposite of pramipexole — it has mediocre efficacy in controlling symptoms but it’s a very safe, well-tolerated and convenient therapy.”
Pharma Two B found a synergy between dopamine agonists and MAO-B inhibitors when given together in animal models.
“This formulation significantly reduces the doses of both components. We use very low doses of both agents in a unique, proprietary extended-release formulation that gives us the efficacy of dopamine agonists in controlling movement disorders associated with Parkinson’s but with a much better safety profile,” says Teleman.
After seeing good results in animal models of Parkinson’s, the company moved to human clinical trials.
The Phase III double-blind study, completed in 2021 in the United States and Europe on close to 600 patients, demonstrated that P2B001 works better than its components alone.
Dr. Warren Olanow, CEO of Clintrex Research Corp. and professor and chairman emeritus of the department of neurology at Mount Sinai School of Medicine in New York, tells ISRAEL21c:
“The studies show that P2B001 provides efficacy comparable to full-dose pramipexole as used in the clinic but with reduced sleep-related and dopaminergic side effects. Further, P2B001 has the advantage that it is only administered once a day.”
He adds that the initial dose proved effective. “Unlike dopamine agonists, you don’t need to keep increasing the dose over weeks or months to try to find an effective dose.”
Olanow, past president of the Movement Disorder Society and past editor-in-chief of the journal Movement Disorders, says the studies indicate that P2B001 “is an important consideration for initiating therapy in [Parkinson’s] patients that is effective, safe, delays the introduction of levodopa, and is easy to use. As such, this new treatment should be appealing to both patients and physicians.”
Results of the study have been shared at professional conferences and will be published in a peer-reviewed journal later this year, says Teleman.
The company’s name comes from 505(b)(2), the FDA fast-tracked regulatory path for formulations based on known and existing approved drugs.
Pharma Two B is now seeking a strategic partner to take the drug candidate through commercialization.
“Because this is an early Parkinson’s product, and early Parkinson’s is treated not only by neurologists but also by primary-care physicians, we will need a very large commercial organization to market it,” Teleman tells ISRAEL21c.
This pathway allows relying partially on safety and efficacy data of previously approved drugs that saves time, money and reduces development risk.
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