In the phase 3 TOLEDO trial, treatment with SPN-830 resulted in significantly greater OFF time for patients with Parkinson disease in comparison with those on placebo.
According to an announcement, the FDA has accepted Supernus Pharmaceuticals’ resubmitted new drug application (NDA) for SPN-830, an apomorphine infusion device designed for the treatment of OFF episodes in patients with Parkinson disease (PD). The FDA is expected to reach a decision on whether to approve the therapy by April 5, 2024, the scheduled PDUFA date.1
"We are pleased with the FDA’s acceptance of our NDA resubmission for SPN-830 and look forward to continuing to work with them during their review," Jack Khattar, president and chief executive officer at Supernus, said in a statement.1 "SPN-830 is an important product candidate which, if approved by the FDA, represents a novel and less invasive treatment option for patients with PD."
SPN-830 is an experimental under-the-skin continuous infusion therapy for reducing motor fluctuations in patients with PD between doses of standard levodopa-based therapy. The phase 3 TOLEDO study (NCT02006121), a double-blind, randomized, multicenter trial, served as the supportive data for the NDA. In the study, treatment with SPN-830 resulted in –1.89 hours per day better OFF time for treated patients vs those on placebo, with reductions observed within 1 week of initiating therapy.2
The most recent NDA resubmission, which occurred last month, was in response to the complete response letter the FDA issued to Supurnus in October 2022. At the time, the agency was requiring additional information and analyses related to the device, including labeling, product quality and manufacturing, device performance, and risk analysis.3
The NDA for the infusion device was originally submitted in September 2020 but was met with a refusal to file letter from the FDA in November 2020, which cited an insufficiency in the application. After a Type A meeting between Supurnus and the agency in March 2021, the company resubmitted the NDA in December 2021. However, no additional safety and efficacy clinical studies were required.
The final analysis of TOLEDO featured 106 patients with PD who received either 3-mg/hour to 8-mg/hour dose of apomorphine (n = 53) or placebo saline infusion (n = 53) during their waking hours for a 12-week period. Results showed that treatment with SPN-830 resulted in a reduction of –2.47 (SD, 3.70) hours of OFF time per day compared with –0.58 (SD, 2.80) hours per day for those on placebo (95% CI, –3.16 to 0.62; P = .0025).
At the 2nd Annual Advanced Therapeutics in Movement and Related Disorders (ATMRD) Congress, held by the PMD Alliance from June 8 to 11, 2023, a panel of movement disorder specialists and dermatologists presented a procotol for the management of skin nodules, the most commonly reported infusion-site reaction associated with the use of continuous subcutaneous infusions like SPN-830. All told, the panel suggested that most of these reactions are self-limited, resolve spontaneously, do not limit the successful continuation of treatment, and importantly, can be managed by a treating neurologist without any referral to dermatology or other medical professional.
The roundtable was convened in June 2022 to developed the proposed framework, when they reviewed the current knowledge of infusion-site reactions, discussed their clinical experience with continuous subcutaneous apomorphine infusion associated reactions, and shared their expertise on guiding patients with PD and educating and training clinicians. The presence of a variety of select signs and symptoms—specifically, the timing following the infusion, pruritus, size, erythema, fluctuance, and drainage—were suggested as the key factors to include in the classification of infusion-site reactions. These classifications of these symptoms included asymptomatic, symptomatic but mild, symptomatic but moderate, and symptomatic and severe.4