LEXINGTON, Mass.—The first clinical study of a new drug under development by Concert Pharmaceuticals holds promise for people who suffer from spasticity, a chronic condition that involves painful tensing and spasms of muscles. The biopharmaceutical company’s results from its Phase 1 study of CTP-354 suggest that drug could present significant advantages over currently available treatments for spasticity. Concert is one of several companies working to find a new and more effective treatment for spasticity. GW Pharmaceuticals is planning to launch a Phase 3 trial for its cannabis-based treatment this fall.
“All of the current treatments for spasticity have substantial limitations, both in terms of dosing regimen and efficacy,” Roger Tung, CEO of Concert, tells DDNews. “We think there’s great potential for a medicine that’s easier to comply with and that doesn’t have the sedative effects of the most commonly used treatments.”
Roughly 12 million patients suffer from spasticity worldwide, according to a 2006 estimate by the American Association of Neurologic Surgeons. The condition can result from a wide range of disorders, including multiple sclerosis, spinal cord injury, cerebral palsy, amyotrophic lateral sclerosis, stroke and hereditary spastic paraplegia. Symptoms range from mild muscle tightness to more severe symptoms, including crippling and painful inability to move limbs that can result in disability and diminished quality of life.
Concert’s recent study focused specifically on the treatment of patients suffering from spasticity as a result of spinal cord injury and multiple sclerosis. “We think there are about 250,000 patients in the U.S. that fit those two categories, and we think about half or so are not satisfied with their treatment or are not receiving adequate treatment,” says Tung.
Several oral treatments are currently available to treat spasticity and are used widely, but each has significant drawbacks. Patients typically need to take doses of most of these drugs three to four times a day, which is considered by many to be an overly burdensome dosing regimen. “We understand from talking to physicians and patients that this dosing regimen is very inconvenient for both caregivers and patients,” says Tung. Another shortcoming of current treatments involve their sedative effects, which can impair cognition and cause patients to have difficulty staying awake, preventing individuals from participating in many everyday activities.
Concert conducted a clinical trial that tested multiple dosing levels through a randomized, double-blind, placebo-controlled study of 30 healthy volunteers. The trial was designed to evaluate the safety, tolerability and pharmacokinetics of 10-day repeat dosing of three different amounts of CTP-354. Results showed that the molecule was generally well tolerated, with mild dizziness and drowsiness being the most common adverse effects. No sedation was observed.
“We found that the compound was very well absorbed, with the amount present in blood stream proportional to the amount taken orally,” Tung tells DDNews. “The compound had a very long half-life—about 20 hours—which is in great contrast to the available drugs, which have half-lives of three to four hours.” The study also examined the effect of food on the drug’s effect in patients and found that CTP-354 provided similar exposure under both fed and fasted conditions, suggesting that it can be dosed without regard to meals.
Concert presented the findings of its Phase 1 trial in July at the at the American Neurological Association’s annual meeting.
CTP-354 is a novel, potentially first-in-class drug, but its development is built on a version of a drug initially developed by Merck. The compound L-838417, a subtype-selective GABAA receptor modulator, was discovered by Merck, which profiled the compound extensively in preclinical efficacy models and found potential efficacy against both inflammatory and neuropathic pain. But Merck ultimately abandoned the development of L-838417 because it also demonstrated substantial pharmacokinetic limitations.
Concert was able to apply its expertise in precision deuterium chemistry to use the failed Merck compound to create CTP-354, which it then patented. Concert was able to achieve more favorable pharmacokinetics with the new molecule, even though it retained many of the same chemical qualities of L-838417.
The company plans to move forward soon with multiple Phase 2 clinical trials of CTP-354. “We remain on track to advance the program into Phase 2 testing later this year, initially targeting spasticity in patients with spinal cord injury followed by the start of a Phase 2 trial in multiple sclerosis patients in early 2015,” said Tung.
Tung tells DDNews that he anticipates potential for CTP-354 beyond its use to treat spasticity if the upcoming trials continue to build an attractive profile for the drug. “We view spasticity as offering a very targeted population with a specific medical need, but there may be potential for CTP-354 to treat a range of other conditions,” he said.