FDA needs additional information before approval of ABBV-951
The formulation is the first to offer a nonstop supply of levodopa/carbidopa
The U.S. Food and Drug Administration (FDA) has requested more information about the specialized pump used to administer ABBV-951 (foslevodopa/foscarbidopa), an under-the-skin formulation of levodopa/carbidopa, before it will consider approving the therapy for motor fluctuations in people with advanced Parkinson’s disease.
The agency’s complete response letter comes 10 months after AbbVie, the therapy’s developer, filed the regulatory application based mainly on data from a Phase 3 clinical trial (NCT04380142) of 174 people with advanced Parkinson’s. Data showed ABBV-951 did better than oral tablets of levodopa/carbidopa at keeping motor fluctuations under control over three months.
No additional safety and effectiveness clinical trials of ABBV-951 were required in the response.
“There is an unmet need for people living with advanced Parkinson’s disease as they face daily challenges in managing their condition,” Thomas Hudson, MD, AbbVie’s senior vice president of research and development and chief scientific officer, said in a company press release. “We will continue to work closely with the FDA as part of our commitment to bringing this treatment option to people impacted by this disease as quickly as possible.”
The company said it plans to resubmit the application with the required pump-related information “as soon as possible.”
If approved, ABBV-951 will become the first formulation of its kind to ensure a round-the-clock, nonstop supply of levodopa/carbidopa prodrugs. A prodrug is an inactive compound that’s converted into an active medicine once it’s in the body.
Parkinson’s is caused by the progressive death of nerve cells in the brain that produce dopamine, a chemical messenger involved in movement control.
Benefit of ABBV-951’s continuous, direct delivery
Oral levodopa, a mainstay of Parkinson’s treatment, is a precursor of dopamine. It’s usually used with carbidopa, a molecule that prevents levodopa from being converted into dopamine before it reaches the brain. This way, more levodopa can reach the brain without the dosage needing to be increased.
Over time, the response to levodopa may not last as long as it once did. This means its benefits may wear off before it’s time for the next dose — resulting in so-called off episodes.
As Parkinson’s gets worse, this wearing off can happen more often, which can cause fluctuations in motor symptoms. People taking levodopa may over time also develop dyskinesia, or uncontrolled and involuntary movements.
With oral tablets, the amount of levodopa that reaches the brain can differ from one time to the next. This happens because the digestive system can absorb the medicine differently each time.
Because ABBV-951 is continuously delivered under the skin through a specialized pump, typically placed in the abdomen, it can be absorbed directly into the bloodstream. This means it can deliver more consistent amounts of levodopa to the brain, start working faster, and reduce off times.
The regulatory application submitted to the FDA was supported by positive data from the Phase 3 trial that tested the therapy against oral levodopa/carbidopa and a Phase 3 trial (NCT03781167) that assessed ABBV-951’s long-term safety and effectiveness.
The first Phase 3 study showed the therapy led to a significantly greater increase in daily good on time and a reduction in off time relative to oral levodopa/carbidopa. Good on time refers to when symptoms are successfully controlled without troublesome dyskinesia.
Results from the long-term trial of 244 Parkinson’s patients having motor fluctuations on standard oral levodopa/carbidopa showed ABBV-951 was generally safe and well tolerated over a year of treatment. Participants saw a drop in daily off time by about three hours on average and a comparable increase in daily on time.
Those who’ve completed either of the trials can enroll in the corresponding extension studies (NCT04750226 and NCT04379050), where they’ll be given the therapy for nearly two years.
The most commonly reported side effects included skin reddening and pain at the infusion site, dyskinesia, problems with balance, falls, hallucinations, constipation, and swelling of the hands and lower legs.