Titan Pharmaceuticals (NASDAQ:TTNP), which is awaiting an FDA approval decision for its six-month Probuphine implant to treat opioid dependence, is advancing its ProNeura implant technology against Parkinson’s disease (PD) and other disorders.
“We plan to submit our PD briefing material and request a pre-IND meeting with the FDA before the end of 2015,” Kate Beebe, EVP and chief development officer, says in an interview with BioTuesdays.com.
“If all goes according to plan, we will complete our non-clinical PD studies to enable an IND submission in early 2016 and begin pharmacokinetic and proof-of-concept studies in the second half of the year,” she adds.
Sunil Bhonsle, president, points out that the company also hopes to see signs of efficacy in its studies next year. “We are aiming at a 505 (b) (2) registration route in PD, which is similar to the pathway we took with Probuphine.”
The FDA recently gave Titan’s marketing partner, Braeburn Pharmaceuticals, a PDUFA date of Feb. 27, 2016 for an approval decision on its NDA for Probuphine.
Mr. Bhonsle explains that Titan’s ProNeura platform is a long-term implant delivery technology that has the potential to be used in developing products for the treatment of chronic conditions, where maintaining stable, round-the-clock blood levels of a drug can benefit the patient and improve medical outcomes. Probuphine is the first product to utilize ProNeura, and if approved, will be the first, six-month, subdermal product on the market for the maintenance treatment of opioid dependence.
Probuphine contains buprenorphine, the gold standard in the U.S. to replace methadone for treatment of opioid dependence. U.S. sales of daily oral formulations of buprenorphine were about $1.7-billion in 2014.
However, challenges with sublingual buprenorphine include compliance, variable levels of medication in the blood, and diversion and abuse. Titan’s Probuphine implant is inserted under the skin in the upper arm in a physician’s office and delivers continuous, stable blood levels of buprenorphine for six months.
The Department of U.S. Health and Human Services recently announced that it plans to revise regulations related to prescribing buprenorphine to treat opioid dependence in order to expand access to medication-assisted treatment.
The company’s PD implant contains ropinirole, a dopamine agonist developed by SmithKline Beecham and now marketed as Requip by GlaxoSmithKline. “In my first job in pharma, I worked on the original ropinirole program, so I am quite familiar with it,” Dr. Beebe recalls.
In preclinical primate studies, the ropinirole implant demonstrated sustained plasma ropinirole levels for several months following implantation, controlling PD symptoms without triggering dyskinesias, which are involuntary muscle movements and often occur as a side effect of long-term therapy with levodopa. There was no skin irritation at the implant site.
As many as one million people in the U.S. are affected by PD and the number is expected to almost double by 2030 because of an aging population. There are about 60,000 newly diagnosed cases of PD annually and more than 23,000 people die from the disease each year.
The costs of PD to American society were estimated at $14.4-billion annually, according to a 2013 study by GlobalData, of which treatment costs totaled $8.1-billion and indirect costs $6.3-billion. If costs continue to rise, they could double by 2040, the study suggested.
Dr. Beebe says ProNeura platform also would be ideal in chronic diseases, such as hormonal deficiencies, Type 2 diabetes, attention deficit hyperactivity disorder, benign prostate hyperplasia and pre-exposure prophylaxis therapy for HIV-1 prevention.
“We are reviewing compounds that potentially fit the ProNeura implant profile and conducting early feasibility experiments with the goal to add at least one more product to the pipeline in the next few months,” she adds.
Mr. Bhonsle says Titan also plans to explore other opportunities for the delivery of proprietary compounds through joint development projects and potential licensing of the ProNeura technology.
The company’s shares were uplisted to NASDAQ yesterday. “The timing is very positive for us, going into the approval process for Probuphine, and as we make investors aware of our product pipeline,” Mr. Bhonsle adds.