Q&A: In Parkinson’s disease, a new treatment for ‘off’ periods

Parkinson’s disease is a progressive disorder of the nervous system that affects movement, the Mayo Clinic explains—in the simplest terms—on its website. It develops gradually, sometimes starting with a barely noticeable tremor in just one hand. But while a tremor may be the most well-known sign of Parkinson’s disease, the disorder also commonly causes stiffness or slowing of movement and “off” periods during which little or no movement is possible.

In the early stages of Parkinson’s disease, the face may show little or no expression. Speech may become soft or slurred. Parkinson’s disease symptoms worsen as the disease progresses over time.

Although Parkinson’s disease can’t be cured, medications may markedly improve symptoms. One such is apomorphine, the subject of this month’s Q&A with Anthony Giovinazzo, the president and CEO of Cynapsus Therapeutics and one of its directors.

DDNews: Tell us a bit about the company you serve as president and CEO, when it was launched and what you see as its long-term mission.

Anthony Giovinazzo: Cynapsus Therapeutics is a specialty pharmaceutical company developing a convenient and easy-to-use sublingual (oral) thin film strip for the acute rescue of “off” motor symptoms of Parkinson’s disease. Formerly named Cannasat Therapeutics, the company changed its name to Cynapsus Therapeutics in 2010. Cynapsus’ drug candidate, APL-130277, is an easy-to-administer, fast-acting reformulation of apomorphine, which is the only approved drug (in the United States, Europe, Japan and other countries) to rescue patients from “off” episodes. Cynapsus is focused on maximizing the value of APL-130277 by completing pivotal studies in advance of a New Drug Application (NDA) expected to be submitted in 2016.

DDNews: Most of us are familiar with the tremors characteristic of Parkinson’s disease, but perhaps less so with the “off” periods. Please describe this “silent phase” for our readers.

Giovinazzo: “Off” episodes of Parkinson’s disease (PD) are characterized by acute immobility, occur once to several times daily and endure from one to several hours, cumulatively. These episodes may be triggered when mainstream treatments such as levodopa or enzyme inhibitors enter the bloodstream too slowly, or wear off quickly, or do not enter the bloodstream sufficiently or at all.

DDNews: Prior to the development of Cynapsus’ APL-130277, what have been some of the other attempts to treat Parkinson’s off periods?

Giovinazzo: Apomorphine, a potent dopamine agonist, is the only drug approved specifically for the treatment of “off” periods in patients with Parkinson’s disease. Presently, apomorphine is administered by intermittent subcutaneous injection, usually via a prefilled injection pen or, in some cases outside the United States, by continuous infusion pump. In the past, many companies have attempted to develop non-injectable varieties of apomorphine. These have included tablets, rectal suppositories, syringes to squirt the drug under the tongue, nasal drops and inhalers. All these attempts either failed or were just commercially impractical—they failed to deliver a sufficient amount of the drug into the bloodstream quickly enough to assist the patients and to overcome the drug’s irritant effects.

DDNews: What are the important advantages of your therapeutic?

Giovinazzo: Traditionally, apomorphine administered via injection can result in painful reactions, including irritation and nodules at the injection site (since apomorphine is only stable in a highly acidic formulation). To avoid these limitations, Cynapsus has developed a sublingual thin-film strip system, called APL-130277, which is similar to Listerine Breath Strips. The strip dissolves in about one to two minutes, delivering the drug into the bloodstream in a similar time interval and concentration as an injectable dose. The strip system utilizes the same drug with its acidic ingredients as well as other ingredients that eliminate irritation and enhance the speed of absorption. The treatment aims at relieving many PD patients of the requirement for self-injections, along with the injury and stress this entails. APL-130277 is easier to prepare for placement into the mouth, is designed to eliminate irritation (or reduce it to an insignificant issue), reduce the need or use of caregivers and their time, as well as other benefits.

DDNews: APL-130277 is patented. What important claims are made in the patent?

Giovinazzo: Our patent claims—some of which have issued in the United States and others pending in several dozen countries around the world—protect the idea of a single or multilayer strip with functional ingredients that change the acidity and help enhance the speed of absorption into the bloodstream. Our claims also link these aspects to the actual outcome of what quantity of drug in a specified period of time accumulates in the bloodstream.

DDNews: Your company is focusing on bringing this—your first product—to market quickly and economically. Where are you currently in this process in terms of ongoing development and funding clinical trials?

Giovinazzo: The company recently announced no irritation was observed when testing the APL-130277 sublingual apomorphine formulation in a buccal mucosal irritation model in hamsters, either macroscopically (clinician observation of oral cavity) or microscopically. This study was a required registration study mandated by the U.S. Food and Drug Administration (FDA). We were encouraged with the results and look forward to demonstrating similar results in upcoming human clinical trials planned over the next 24 months. We expect to submit an NDA to the FDA in 2016.

DDNews: What is your estimation of the eventual market for APL-130277?

Giovinazzo: We estimate that the potential peak annual sales for APL-130277 could be $700 million to more than $1 billion for the U.S. and major European markets, based on three factors. First, the current prevalence of Parkinson’s disease in the U.S. is about 900,000 cases, of which approximately 25 to 50 percent could be candidates for APL-130277. Second, two surveys of neurologists revealed that a sublingual form of apomorphine is needed by physicians for their patients and that they would prescribe the drug for far more moderate and severe Parkinson’s patients than currently receive the injectable form of apomorphine. Third, a survey of U.S. HMOs and insurers showed that they would be willing to place APL-130277 on their formularies and that they would be willing to reimburse at a fair price.

DDNews: Do you expect Cynapsus to explore additional opportunities for its patented dosage form?

Giovinazzo: At this time, we are exclusively focusing on the development of APL-130277 and targeting the Parkinson’s patient population.

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Anthony Giovinazzo is a director and the president and CEO of Cynapsus Therapeutics, with more than 18 years of experience in international pharmaceutical drug development, private and public financings and merger-and-acquisition transactions. Giovinazzo has successfully managed pre-IND, IND/CTA, end of Phase 1-2, CTD/NDA submissions and negotiations with FDA and EMEA/CPMP. He has identified, licensed and overseen the development of eight biotech drug development candidates, preclinical to Phase 3, for the treatment of Parkinson’s disease, Alzheimer’s disease, anxiety, neuropathic pain and nausea. Giovinazzo led the sale of Nova Molecular Diagnostics to Variagenics Inc. through the public listing of Variagenics, which resulted in significant above-average returns to investors. As CEO, he also led the acquisition of Cita Neuropharmaceuticals by Vernalis Plc, which resulted in a substantial multiple return to venture investors. He is one of the inventors of the original APL-130277 intellectual property that was acquired by the corporation.