After receiving FDA approval last year for its Probuphine implant as a maintenance treatment for opioid addiction, Titan Pharmaceuticals (NASDAQ:TTNP) is employing its ProNeura drug delivery technology to develop an implant to treat Parkinson’s disease.
“The merits of continuous, non-fluctuating drug delivery of dopamine and dopamine agonists have shown to minimize side effects like dyskinesias in non-clinical and clinical studies,” Kate Beebe, EVP and chief development officer, says in an interview with BioTuesdays, referring to abnormal involuntary movements often associated with Parkinson’s.
The disease is characterized by the loss of dopamine, which alters activity in the brain region impacting movement and motor function and is treated with drugs designed to replace or mimic dopamine in the brain. After several years of treatment, however, these drugs can lose their benefit and trigger serious side effects in up to 80% of patients.
Parkinson’s affects approximately one million people in the U.S. and 10 million worldwide and the numbers are expected to double in the next few decades from an aging population. The disease is the 14th leading cause of death in the U.S., with an annual cost to American society of $14.4-billion.
There are about 60,000 new cases of Parkinson’s in the U.S. each year, leading to some 23,000 deaths. The exact cause and reason for disease progression is unknown and there is no cure.
April is Parkinson’s awareness month and the newly formed Parkinson’s Foundation, arising from a merger of the National Parkinson Foundation and Parkinson's Disease Foundation, is promoting various outreach programs to the Parkinson’s community.
Among other things, the foundation is raising awareness of the disease by sponsoring Moving Day walks in various cities for patients and caregivers, to emphasize the importance of exercise in managing the symptoms of the disease.
The foundation has a vast nationwide network of Parkinson’s Centers of Excellence where movement disorder experts are available for consultations, as well as allied health professionals, about how to live with the disease and improve the quality of life for patients and caregivers.
Dr. Michael Okun, national medical director of the Parkinson’s Foundation, points out that Parkinson’s is not one disease, but rather a group of disorders with similar symptoms, without one underlying etiology.
“About 10% of cases arise from a single gene defect, leading many investigators to suggest that genes load the gun and the environment pulls the trigger.”
Dr. Okun, who also is Professor and chairman of neurology at the University of Florida, contends that Parkinson’s is the most complex disease in clinical medicine, with more than 20 motor and non-motor symptoms as well as dozens of pharmacologic, non-pharmacologic and surgical treatment options.
In addition, the disease is dynamic and the symptoms and treatments change over time. Common symptoms include tremors, stiffness and slowness as well as depression, anxiety, sleeping disorders and sexual dysfunction.
“We can treat Parkinson’s with behavioral approaches, such as physical and occupational therapy, dopamine replacement strategies, deep brain stimulation and various other therapies,” he suggests. And as researchers attempt to design new treatments, it’s important to keep in mind the non-motor symptoms that patients incur affect quality of life more than the motor symptoms.
“When you think about the disease, you need to think about three buckets of treatments,” he points out. “One bucket is meaningful symptomatic therapies to improve patients’ symptoms today. Another bucket is treatments to potentially slow disease progression. We’ve had 20 years of looking at slowing disease progression and not found a single therapy to place in this bucket yet. And the final bucket is a cure, which is furthest away but might be possible with several of the genetic causes of Parkinson’s.”
According to Dr. Okun, an important focus in treatment today, where therapies are not “moving the needle enough” is walking, talking, thinking and improving the mood of patients.
And the next horizon of therapy, he suggests, is personalized medicine based on the specific profile of a patient’s symptoms or groups of symptoms. “Can we design a pharmacological or surgical or combination therapy to address the often very specific symptoms of an individual patient?” he asks.
Meanwhile, Titan’s Dr. Beebe says an implant device would benefit patients who do not need frequent change in doses of medication. “Not all patients need frequent dose changes, especially in the intermediate stages of the disease.”
Titan’s ProNeura long-term drug delivery platform consists of an active pharmaceutical ingredient uniformly distributed throughout an ethylene vinyl acetate co-polymer matrix and blended and extruded into a match-sized device.
A trained and certified health care provider inserts the implant subdermally in the inner side of the upper arm. Drug is released continuously into a patient's body through the process of dissolution, resulting in a stable level of medication in the blood and avoiding peaks and troughs of oral dosing.
Titan’s Parkinson’s implant contains the active ingredient, ropinirole, which is sold by GlaxoSmithKline as Requip, and has the potential to deliver continuous non-fluctuating levels of dopamine agonists for several months from a single treatment.
The company submitted an IND to the FDA in January and hopes to begin a Phase 1 pharmacokinetic study in mid-2017 to assess safety and tolerability over a three-month period.
The study will enroll Parkinson’s patients receiving adjunctive therapy with oral ropinirole and determine whether the ropinirole implant can replace the oral therapy.