Anthony Giovinazzo
“If I had asked for a gift, I couldn’t have wished for anything better,” says Anthony Giovinazzo, president and CEO of Cynapsus Therapeutics (OTCQX:CYNAF; TSX-V:CTH).
He was referring to a recently completed healthy volunteer pilot crossover trial, CTH103, which compared Cynapsus’ APL-130277, a sublingual thin film strip formulation of apomorphine, with a commercially available injectable formulation of apomorphine as a rescue therapy for patients suffering from Parkinson’s disease (PD) with debilitating motor complications.
“We are enthusiastic about the results, which confirm that our sublingual thin film strip formulation is effective at delivering apomorphine with the potential to reach efficacious plasma levels, but with what appears to be an improved side effect profile, compared with the subcutaneous injectable formulation,” he adds.
Injectable apomorphine, which is sold as Apokyn in the U.S. and Apo-go in Europe, is currently the only rescue therapy that quickly restores movement and freedom to PD patients. However, the injection often delivers too much drug, which causes nausea, vomiting and hypotension.
While APL-130277 did not achieve exact bioequivalence with the injection in the CTH103 study, “we obtained something we think may be better, namely a potentially better adverse event profile, which we hope will translate into a clinical benefit for patients and could mean that more patients will adopt the strip,” Mr. Giovinazzo contends.
In addition, he says APL-130277 seems to have reached a plasma concentration normally associated with an “on,” or normal functioning, which was close to the same timeframe as the injection, which also is important from a patient perspective.
PD is a neurodegenerative disease that results from the death of neurons in the region of the brain that controls movement. The degeneration creates a shortage of an important brain signaling chemical, or neurotransmitter, known as dopamine, rendering patients unable to move normally.
Parkinson’s disease
Apomorphine is the only drug approved specifically for the treatment of hypomobility, which is known as “off” episode freezing, in patients with advanced PD.
In an “off” state, a patient becomes very stiff, slow and may even be unable to move for an extended period of 30 to 120 minutes, or longer. In advanced PD, “off” episodes become more frequent and are sporadic, limiting the ability of patients to move and engage in daily life. Unpredictable “on-off” fluctuations also can put patient’s wellbeing at risk.
APL-130277 is being developed to rescue patients from “off” episodes. “The idea is to get patients to “on” episodes as quickly as possible with an oral, easy-to-use film strip so that they can move at will,” Mr. Giovinazzo explains. “We are attempting to restore movement with ease.”
He says results of the CTH103 study are an “important de-risking event for our product and set the stage for completing, in the next two years, the clinical requirements for qualifying APL-130277 for a 505(b)(2) New Drug Application.”
In addition, he says the data indicate that APL-130277 may have advantages over an injectable product by reducing the frequency and intensity of side effects, including nausea and vomiting, versus those commonly reported for a subcutaneous injectable formulation.
The results also suggest that APL-130277 exhibits comparable time to maximal concentrations in the blood and therapeutic plasma levels that are similar or longer than those seen following subcutaneous injection, he adds.
CTH103 Results: 10mg strip crossover with 2mg injection
CTH103 Results: 15mg strip crossover with 3mg injection
“We are indebted to the Michael J. Fox Foundation for Parkinson’s Research, which provided the bulk of funding for the CTH103 trial,” Mr. Giovinazzo says.
In a report, analyst Nathan Cali of Noble Financial wrote that if approved, APL-130277 could provide patients “with a daily use, non-invasive therapeutic, with a better safety profile, longer acting oral formulation intended to treat ‘off’ episodes, versus a currently approved underutilized, difficult to deliver and painful to deliver and tolerate potent rescue therapy.”
He rates the stock as a “buy,” with a 12-month price target of $2.25. Shares of Cynapsus closed at $1.09 on Friday.
Mr. Giovinazzo says Toronto-based Cynapsus is in the process of submitting a data package to the FDA and hopes to have a meeting with the agency in the second quarter this year. “Assuming concurrence, we expect that results of the CTH103 study will enable us to proceed directly to the completion of two small efficacy studies and a safety study, in patients with PD.”
The company’s plan is to design a clinical registration program for APL-130277 that demonstrates efficacy as measured by both time to “on” and duration of “on” in PD patients, with claims for fewer and less intense adverse events as a possible added feature.
He says the company intends to conduct two efficacy studies this year in “off” episode management, enrolling apomorphine-naive and apomorphine-experienced PD patients.
In addition, Cynapsus intends to conduct a safety study in apomorphine-naive Parkinson’s patients in 2015, with a possible New Drug Application filing in the first half of 2016.
Apokyn’s side effects have resulted in a small market of about $70-million a year worldwide for the injection. Consultants retained by Cynapsus have surveyed patients, neurologists and insurers, concluding that an oral, easy-to-use film strip could achieve sales of $240-million or more in the U.S. alone, based on improved tolerability.
Mr. Giovinazzo says several global and specialty pharmaceutical companies have conducted due diligence on the company’s intellectual property. Serious partnering discussions could begin either following this year’s two efficacy studies or the safety study next year, he adds.
