The approval marks the first and only of its kind, with the treatment anticipated to be commercially available by prescription in the US sometime in Q1 of 2019.
Ron Cohen, MD
The FDA has approved inhaled levodopa (Inbrija, Acorda Therapeutics) for the intermittent treatment of off episodes in patients with Parkinson disease who are taking carbidopa/levodopa.1
The approval, according to manufacturer Acorda, makes this the first and only approval of its kind. The formulation is based on Acorda’s ARCUS technology platform for inhaled drug delivery. The treatment is anticipated to be commercially available by prescription in the US sometime in Q1 of 2019.
“Today’s approval of INBRIJA marks a major milestone for both Acorda and the Parkinson’s community, for whom we are gratified to have developed this much-needed therapy,” Ron Cohen, MD, Acorda President and CEO, said in a statement. “This milestone resulted from over two decades of research and development, beginning in the laboratory of Dr. Robert Langer at Massachusetts Institute of Technology, through years of enormous perseverance and ingenuity by the entire Acorda team.”
The FDA’s decision was made based on data from a clinical trial program which included almost 900 patients with Parkinson who were taking a carbidopa/levodopa regimen experiencing OFF periods. In the phase 3 SPAN-PD trial, the inhalation therapy met its primary end point, with patients showing a statistically significant improvement in motor function at 12 weeks, as measured by a reduction in Unified Parkinson’s Disease Rating Scale (UPDRS) Part III score. At 30 minutes post-dose, the 84-mg inhaled treatment group (n = 114) experienced a reduction of 9.83 points compared to a reduction of 5.91 points for those on placebo (n = 112; P = .009). The onset of action was observed as early as 10 minutes.
The most common adverse events (AEs) with inhaled levodopa (occurring at least 5%) in the pivotal trial were cough (15%), upper respiratory tract infection (6%), nausea (5%) and sputum discoloration (5%).
“Despite being on treatment, patients may experience OFF periods as Parkinson’s progresses, which can be disruptive,” said Todd Sherer, PhD, the CEO of The Michael J. Fox Foundation. “The Foundation provided funding for the early clinical development of INBRIJA because patients told us that OFF periods were one of their most serious issues. We knew we had to help address this unmet need, and this approval is a significant step forward for the community as it provides a new option to manage these gaps in symptom control.”
The treatment was also assessed in a phase 3 long-term, active-controlled, randomized, open-label study that included 398 patients. It was assessed for safety and tolerability over 1 year. This study showed the average reduction in forced expiratory volume in 1 second (FEV1) from baseline was the same (-0.1 L) for the inhaled levodopa and observational cohorts.
Patients with chronic obstructive pulmonary disease (COPD), asthma, or other chronic respiratory diseases within the last 5 years were excluded from the open-label study.
“In the clinical study program, INBRIJA established its safety profile and demonstrated clinically meaningful improvements in motor function, as measured by the UPDRS Part III,” said Robert A. Hauser, MD, MBA, a professor of neurology and the director of the Parkinson's Disease and Movement Disorders Center at the University of South Florida. “INBRIJA helps address a significant unmet need for people with Parkinson’s, and we look forward to adding this new treatment option to our armamentarium.”
The inhaled therapy is contraindicated for those who take or have taken a nonselective monoamine oxidase inhibitor, such as phenelzine or tranylcypromine, within the last 2 weeks.
“I’m delighted that INBRIJA has been approved and may be added to patients’ existing Parkinson’s medications for on-demand use, based on individual patient need,” said Burkhard Blank, MD, Chief Medical Officer of Acorda. “We thank the FDA for a constructive dialogue throughout the development program and their partnership during the review cycle. We especially thank all those who volunteered for the INBRIJA clinical trials, without whose commitment new medications could not be developed. And we are grateful for the people living with Parkinson’s, their care partners, researchers, clinicians and advocacy groups, who have all collaborated with us to help achieve this milestone.”
1. Acorda Therapeutics Announces FDA Approval of INBRIJA™ (levodopa inhalation powder) [press release] Ardsley, NY: Acorda Therpaeutics, Inc; Published December 21, 2018. businesswire.com/news/home/20181221005620/en/Acorda-Therapeutics-Announces-FDA-Approval-INBRIJA™-levodopa. Accessed December 22, 2018.