After gaining widespread attention with its FDA-approved Probuphine implant for the maintenance treatment of opioid addiction, Titan Pharmaceuticals (NASDAQ:TTNP) is setting out to develop an implant to treat Parkinson’s disease (PD).
Last week, Titan initiated screening of the first patients in a Phase 1/2-dose escalation trial with an implant containing the drug ropinirole, a dopamine agonist sold by GlaxoSmithKline for PD under the brand name, Requip.
“We expect to enroll about 20 patients with idiopathic PD at three sites in the U.S. in four cohorts of five patients each,” Dr. Kate Beebe, EVP and chief development officer, says in an interview with BioTuesdays.
“Patients in the first cohort will receive one implant, patients in the second cohort two implants, the third cohort three implants, and patients in the fourth cohort will receive four implants, which we expect should cover the prescribed range of daily oral doses of ropinirole,” she adds.
Data from the first patient cohort should be available in early 2018, following completion of three months of treatment. The study should be finished by the end of 2018.
Dr. Beebe explains that PD is characterized by the loss of dopamine, which alters activity in the brain region impacting movement and motor function, as well as mood, insomnia, anxiety, appetite and other non-motor symptoms.
The disease is treated with drugs designed to replace or mimic dopamine in the brain. But after several years of daily dosed treatment, these drugs can lose their benefit and trigger serious side effects in up to 80% of patients, she adds. “This is where we think our implant can play an important role.”
According to Dr. Beebe, PD affects as many as one million people in the U.S., with that number expected to almost double by 2030 because of the aging population. In addition, there are some 60,000 newly diagnosed cases of PD annually and more than 23,000 die from PD each year.
A 2013 study by the Parkinson’s Action Network, National Center for Health Statistics determined that PD costs American society some $14.4-billion annually, comprised of treatment costs of $8.1-billion and indirect costs of $6.3-billion, with total costs expected to double by 2040.
Dr. Beebe says Titan’s ropinirole implant, which like Probuphine is based on the company’s ProNeura drug delivery platform, has been evaluated in a PD animal model.
The ProNeura technology uniformly distributes an active pharmaceutical ingredient throughout an ethylene vinyl acetate polymer, which is blended and extruded, to produce a rod shaped implant. The implant facilitates a controlled rate of drug delivery, is virtually 100% bioavailable, with no reservoir and no risk of drug dumping.
The non-clinical PD model results were presented at the 19th International Congress of Parkinson's Disease and Movement Disorders in June 2015. Dr. Beebe says the implant demonstrated sustained plasma ropinirole levels for several months following implantation, with no local skin irritation at implant site. The implant also controlled PD symptoms without triggering dyskinesias, or involuntary muscle movements.
She says the goals of the Phase 1/2 trial include characterizing the pharmacokinetic profile of the ropinirole implants, evaluating safety and tolerability of up to four dose levels and exploring potential signals of efficacy using established disease-specific assessment scales.
Sunil Bhonsle, president and CEO says the company is continuing discussions with potential partners to distribute its Probuphine implant in Europe. “We’re focused on areas in Europe where the active ingredient in the implant, buprenorphine, is already being sold. There’s also a potential for commercial distribution in Australia and some areas in Asia.”
The company plans to submit a marketing authorization application for Probuphine to the European Medicines Agency in the fourth quarter this year. Probuphine is sold in the U.S. by Braeburn Pharmaceuticals.
Beyond PD, Mr. Bhonsle says an implantable triiodothyronine (T3) product for the treatment of hypothyroidism is completing non-clinical development focused on formulation optimization.
Titan also is collaborating with the Walter Reed Army Institute of Research and the Southwest Research Institute in the early non-clinical evaluation of the implant drug delivery platform in malaria prophylaxis, and with Opiant Pharmaceuticals (NASDAQ:OPNT) in the feasibility assessment of an implant to provide continuous, long-term treatment with an opioid antagonist for the potential prevention of opioid relapse and overdose in patients with opioid use disorder, he adds.
Other ProNeura feasibility evaluations are ongoing in the area of chronic pain treatment with a peripherally acting, Kappa opioid receptor agonist, and in the treatment of Type 2 diabetes with currently approved peptides.