Pharma Two B Announces Positive Results in Phase IIb Clinical Study of P2B001 for Early Stage Parkinson’s

Rehovot, Israel based Pharma Two B Ltd. is reportedly mulling issuance of an IPO after announcing successful results in the company’s Phase IIb pivotal study of P2B001 for treatment of early stage Parkinson’s Disease (PD) which is boosting the company’s confidence in taking its quest for financing to the next level with an IPO or partnership deal to supply the cash needed for further clinical studies.

The study notes that animal model research supports the therapeutic advantage of combining low doses of the monoamine oxidase inhibitor rasagiline and the dopamine agonist pramipexole, and suggest further improvement when both are administered in a sustained fashion. P2B001 is a combination of low dose pramipexole and low dose rasagiline administered as a proprietary sustained release formulation. Both rasagiline and pramipexole are well known marketed drugs for Parkinson’s disease with a good safety profile. combining the drugs in low doses and controlled release may provide better symptom management than the existing drugs alone or together.

The study, entitled “A Phase IIb, Twelve Week, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study, To Determine the Safety, Tolerability and Efficacy of Two Doses of Once Daily P2B001 in Subjects with Early Parkinson’s Disease”, met primary and secondary clinical endpoints for both of the investigated dose combinations.

P2B001 is Pharma Two B’s lead product for Treatment of Parkinson’s Disease and the lead product candidate of the privately held company which is focused on developing innovative therapeutics based on previously approved drugs. Pharma 2 B develops clinically differentiated and value-added products, based on synergistic combinations of two or more existing drugs, acting in complementary biological mechanisms that enable use of unique low doses, while maintaining high therapeutic benefit
and providing high clinical value and shorter regulatory pathways. The company develops products in two therapeutic areas with great unmet needs – Parkinson’s disease (PD) and Cancer.

A Pharma Two B Ltd. release notes that specifically, the study results showed both overall improvement of 5.97 UPDRS points for the high dose combination, leading to a significant change of 4.67 UPDRS points compared to placebo (P<0.001); and overall improvement of 5.14 UPDRS points in the low dose combination, leading to a significant change of 3.84 UPDRS units compared to placebo (P<0.001).

A Favorable Safety Profile

One hundred and forty-nine patients participated in the study which was conducted at 29 clinical sites throughout the US and Israel. C. Warren Olanow, M.D., Professor of Neurology and Neuroscience at the Mount Sinai School of Medicine in New York, and CEO of Clintrex LLC, and Karl Kieburtz, M.D., Professor of Neurology, Public Health Science and Environmental Medicine at the University of Rochester and President of Clintrex LLC were clinical leaders of the study.

An estimated seven to ten million people worldwide are living with Parkinson’s disease (PD), which is the second most common neurodegenerative disease after Alzheimer’s. The National Institutes of Health estimates that about one million Americans have Parkinson’s disease, and some 50,000 Americans are diagnosed with new Parkinson’s cases annually.

A slowly progressing neurodegenerative disorder, Parkinson’s is caused by death of dopaminergic neurons in in a region of the midbrain called substantia nigra for reasons unknown. Dopamine is a neurotransmitter that carries signals between the areas of the brain that regulate and control smooth, purposeful motor movement when performing routine tasks like eating, writing and shaving.

Common first symptoms of Parkinson’s include tremors, rigidity and slowed movement (bradykinesia). While the motor symptoms can be treated with medication, the disease’s progression cannot be prevented, and benefits of medication may fade as the disease progresses, and/or side effects can become problematic. People with late stage Parkinson’s disease have many disabling symptoms including: rigid or stiff muscles, and impaired posture and balance, trouble walking, and muscle stiffness and tremors in the arms and hands that make it difficult to perform everyday tasks.

In addition, Parkinson’s disease may cause non-motor symptoms such as sleep problems, depression, and anxiety, which are not alleviated by current Parkinson drugs.

The current and longtime gold standard treatment for PD has been Levodopa, but long term Levodopa use is associated with severe side effects over time including dyskinesia (uncontrolled involuntary movement) and off periods (hours of time when the patient suffers from a return of Parkinsonian features). To delay this situation, physicians often prescribe other drugs at the disease’s early stage in order to delay introduction of levodopa. Though these drugs are not associated with motor complications, they are not as effective as Levodopa and can also cause serious unwanted side effects. There is consequently a major unmet medical need for a safe and effective treatment of early PD that allows delay of Levodopa introduction of and risk of Levodopa associated motor complications.

“Pharma Two B’s P2B001 combines two non-Levodopa drugs that have been individually approved for the treatment of early stage Parkinson’s disease, in a sustained release profile. Given as low dose monotherapies, the anti-Parkinsonian effect of these drugs given individually is limited, while in higher doses they can be associated with potentially serious side effects. In preclinical studies, we observed that a low dose combination of these two drugs administered in a sustained release formulation has synergistic effects leading to notable efficacy and a very good safety profile,” explains Pharma Two B CEO, Dr. Nurit Livnah. “We are now thrilled to confirm similar results in our Phase IIb clinical study, showing that Pharma Two B’s combination product has a significant anti-Parkinsonian effect in both low doses tested, with a very good safety profile. Moreover, P2B001 provided benefits similar to those observed with the higher doses currently prescribed to PD patients. This means that with P2B001, PD patients may be able to achieve clinical benefits comparable to current treatments but with lower doses and less risk of serious side effects.”

According to Dr. C. Warren Olanow, “The demonstration that significant anti-Parkinsonian benefits can be achieved with once a day administration of low doses of a combination extended release product provides an opportunity to effectively treat PD patients in the early stages of the disease with a very low risk of inducing serious side effects. This logical and simple approach should be of value for early PD patients.”

“The exciting news today is pivotal for Pharma Two B, which has a defined goal to provide an effective therapy with minimal side effects that will positively impact the lives of those with early stage PD. Based on the positive results of the Phase IIb pivotal study, we can now move forward to immediately initiate the single Phase III clinical trial needed for registration, via the 505(b)(2) pathway, and to bring P2B001 to market. We are focused, determined and ready to continue working hard to achieve this end goal. We are currently examining ways to finance the Phase III trial either through IPO or a strategic agreement with a marketing partner,” says Pharma Two B chairman of the board of Mr. Ehud Marom.

P2B 001 is a combination product consisting of two drugs with complementary mechanism of action. Combination products contain two or more drugs in one dosage form, in an optimized ratio/dose, and an individually adapted release profile for each of the components. Combination products are generally formulated using either tableting or microencapsulation techniques. In the case of microencapsulation, for example, separate beads for each component, with a release profile adapted to its pharmacokinetic properties, are formulated independently and packed in one capsule.

Advantages of combination products include increased clinical value- synergy between the drug components leading to greater therapeutic effect while allowing lowering the doses of each component in turn leading to better prospects for improved safety profiles with fewer and lesser intensity side effects. One dosage forms containing multiple drugs, taken once daily result in better patient compliance, and the use of basic compounds already established and accepted leads to increased acceptance by physicians, patients and insurance companies and a shortened regulatory pathway, ie: the US FDA’s 505(b)2 regulatory pathway intended for previously approved drugs, being developed for different indication, different dosage form/strength, or in combinations. This pathway is defined in the FDA as a new drug application (NDA) containing safety and efficacy studies that were not conducted by the applicant.

This pathway allows the applicant to rely on safety and efficacy findings of previously approved drugs, however requires preclinical and clinical data demonstrating that the differences from the reference drug do not compromise safety and efficacy. This approach may potentially save pharmaceutical sponsors both time and money.

Pharma 2 B notes that a remarkable synergy between the drug components of P2B001 was demonstrated in preclinical studies using two independent models, with the complimentary effect further enhanced by the slow release formulation developed for the product. The optimal release profile enhances the clinical effect by more than 50 percent by increasing the time that the component can act in synergy. The combination showed a notable pharmacological advantage with no toxicity. In addition, development of optimal release profile led to an increase in the duration of mutual action of the components resulting in further increase efficacy.

P2B001 was discovered after intensive screening of various drugs with different mechanisms of action, aimed to identify drugs that complement each others action and work in synergy. Once identified, P2B001 was researched intensively to explore its safety and effectiveness, and to determine the optimal doses and formulation.

Development of P2B001 is intended to provide a combination of low dose drugs, in an improved formulation, that is expected to be more effective in controlling Parkinson’s disease symptoms than each of the drugs taken alone or the current available commercial drugs taken together. A Phase IIb clinical trial with P2B001 is currently ongoing, in the US and Israel.

A Phase II Clinical Trial entitled “A Phase 2B, Twelve-week Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study, To Determine the Safety, Tolerability and Efficacy of Two Doses of Once Daily P2B001 in Subjects With Early Parkinson’s Disease” will enroll a total of 150 recently diagnosed patients, between the ages of 35 and 75. The study was performed at 25 leading clinical sites in the US and five sites in Israel. Patient recruitment to the study was completed and enrollment to this study is now closed.

Phase I / PK Clinical Trial

After completion of the pre-clinical evaluation of P2B001 that revealed the synergy between the combination components and the significant contribution of the sustained-release formulation which further enhances the efficacy, Pharma Two B developed an oral dosage form for the product, consisting of sustained release profiles for both components. The company tested P2B001 in a Phase I / PK clinical trial — a 4-arm, cross-over study in which the components in their currently available commercial forms, alone or together, were compared to P2B001. Pharma 2 B reports that the study was highly successful, with results also indicating a very good safety and PK profiles.

Sources:
Pharma Two B
National Institutes of Health

Image Credits:
Pharma Two B