Cynapsus Therapeutics, currently conducting a pivotal Phase 3 clinical study of its sublingual formulation of apomorphine to treat “OFF” episodes in Parkinson’s disease (PD), is teaming up with the Michael J. Fox Foundation for Parkinson’s Research (MJFF) for a sub-study that will use wearable technology to gather and analyze patient data on the drug’s effect and disease progression.
The new apomorphine formulation APL-130277, as well as the techonology-enabled sub-study, which will include software developed jointly by MJFF and Intel, were the focus of a recent Cynapsus presentation at the 10th World Congress on Controversies in Neurology (CONy) March 17-20 in Lisbon, Portugal.
Dopamine replacement therapy is the standard hallmark of Parkinson’s therapy. However, as the disease progresses and more dopamine-producing neurons are lost, the efficacy window of this therapy shortens and patients experienced the so-called OFF episodes, characterized by motor-impairment symptoms that are thought to occur when dopamine levels fall below a critical threshold. Apomorphine, approved as a subcutaneous formulation, is a rescue therapy that brings the patient back to “ON” mode.
For five years Cynapsus has been developing a fast-acting, easy-to-use sublingual (under the tongue) thin-film formulation of apomorphine, APL-130277. Currently, the drug’s effectiveness and safety for Parkinson’s patients experiencing OFF episodes are being evaluated in two Phase 3 clinical trials, the CTH-300 and CTH-301 studies. Anyone interested can find the website here for more information about the trials and eligibility requirements.
The CTH-300 placebo-controlled study (NCT02469090) will evaluate APL-130277 in 126 patients with Parkinson’s who have at least one OFF episode every day, and a total OFF time of at least two hours per day. The trial will last 12 weeks and, when it is complete, participants may join the CTH-301 trial (NCT02542696), which will study the drug’s effect on an estimated 226 Parkinson’s patients with the same characteristics stated above for six months of treatment.
Some of the patients enrolled in the Phase 3 studies will participate in a sub-study, using a wearable device and a Fox Insight smartphone application, developed jointly by MJFF and Intel Corporation, to track data on movement and the effect of medication. This pilot study aims to understand how clinical studies can benefit from data science technologies, which are a faster way to assess disease progression and have the potential of speeding up the clinical development of new drugs.
In this case, this technology platform will serve as a proof-of-concept that data science technologies can contribute to the accurate assessment of Parkinson’s in interventional clinical studies.
“The data analytics capabilities enabled by Intel and The Michael J. Fox Foundation will allow us to better evaluate how APL-130277 is helping patients. As our Phase 3 clinical trials progress and we move toward gaining FDA approval of APL-130277, we plan to work closely with Intel and The Michael J. Fox Foundation to use this technology to improve the lives of patients with Parkinson’s disease,” said Dr. Albert Agro, Cynapsus’ chief medical officer, in a press release.
Parkinson’s News Today had the opportunity to interview Anthony Giovinazzo, president and CEO of Cynapsus Therapeutics, and Dr. Warren Olanow, member of the Cynapsus Clinical Advisory Board and professor of neurology at Mount Sinai School of Medicine in New York City.
When asked if APL-130277’s main strength is its sublingual formulation, Giovinazzo said, “As an under-the-tongue formulation of apomorphine, APL-130277 is designed to be both easy to self-administer and to avoid many problems associated with injection. Because apomorphine is highly acidic, injected forms are painful and cause injection-site reactions. Our under-the-tongue formulation neutralizes the acidity of apomorphine and dissolves in a few minutes, delivering the effective dose to the patient.
“The difficulty of preparing and administering the injection, needle aversion and side effects associated with injection have prevented apomorphine from becoming widely used,” Giovinazzo said. “For patients experiencing OFF episodes, providing apomorphine in an oral sublingual form like APL-130277 is likely to make a major difference in their lives. This is an example of how important it is to look at the context of a therapy for it to be broadly accepted and useful. Although we are using the same therapeutically active molecule as the injected form, solving the problems of administration is the critical difference of APL-130277.”
Olanow emphasized that “apomorphine is a very effective anti-Parkinson drug,” and summarized what he believes to be the strengths of APL-130277. “It is very effective, … it has a methodology for reducing the cutaneous side effects, it doesn’t require an injection, it is a simple strip you put under your tongue, and it would be easier to initiate titration.”
As for partnering with MJFF, Giovinazzo said “Cynapsus has collaborated for years with the Michael J. Fox Foundation to understand and address specific patient needs. We recently announced together with the Fox Foundation that we will begin working together to incorporate wearable device technology and big data approaches into Cynapsus’ Phase 3 clinical studies of APL-130277.
“In theory, smartwatches could provide more objective data than a patient’s journals or a doctor’s observations or assist patients in recording symptoms,” Giovinazzo said. “Smartwatches could also help accumulate more information in a shorter period or provide large amounts of data from a smaller number of patients, which could reduce the time and cost required for development of new therapies.”
Olanow, referring to MJFF’s large database of Parkinson’s patients willing to participate in clinical trials, said, “If you are doing a study such as this particular trial, you can develop a relationship with Michael J. Fox and access that database and hopefully get patients who would qualify for your study and recruit them in a much faster time than you might be otherwise able to do.”
When asked about the relationship of Cynapsus with patients and advocates, Giovinazzo said, “Listening to patients is critical for the successful development of new therapies that appropriately address specific patient needs. We have commissioned surveys focused specifically on how OFF episodes affect both patients and their caregivers to help us understand patient preferences and ensure that our therapy, APL-130277, addresses clearly defined needs.”
“One of the current challenges of developing therapies for the specific problem of OFF episodes is that awareness of the problem of OFF episodes is low among patients, caregivers, and even clinicians. We are actively supporting programs aimed at raising awareness among those audiences, as we hope that broader awareness of the significance of this aspect of the disease will help encourage additional efforts to find solutions,” Giovinazzo said.
The complete interview with Olanow is in the video below.