After Supernus met with the FDA earlier this year, the company believes it has addressed the agency’s requests mentioned in its complete response letter delivered in October 2022.
According to a recent announcement, Supernus Pharmaceuticals has resubmitted its new drug application (NDA) for its investigational apomorphine infusion device, otherwise known as SPN-830, for the continuous treatment of motor fluctuations in patients with Parkinson disease (PD).1
In October 2022, the FDA issued a complete response letter (CRL) to Supernus for SPN-830, requiring additional information and analyses related to the device, including labeling, product quality and manufacturing, device performance, and risk analysis.2 Additionally, the agency mentioned that NDA-required inspections were not met in a timely manner because of travel restrictions from the COVID-19 pandemic.
In its latest update, Supernus believes it has addressed the FDA’s questions raised in the CRL and will continue to work closely with the FDA as it continues to review the application. 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.
"SPN-830 represents a novel and less invasive therapy approach for patients with PD who are seeking a convenient option in the form of a continuous subcutaneous infusion of apomorphine," Jack Khattar, president and chief executive officer at Supernus, said in a statement.1 "We look forward to continuing our effort with the FDA throughout the NDA review process to bring a promising alternative to patients and their families."
The NDA for the infusion device was originally submitted by Supernus 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 Supernus and the agency in March 2021, the company resubmitted the NDA in December 2021. However, no additional safety and efficacy clinical studies were required.3
Data from the phase 3 TOLEDO trial (NCT02006121), published in Lancet Neurology in 2018, were the main basis for the NDA. At the conclusion of the double-blind, randomized, multicenter study, treatment with SPN-830 was associated with a difference of –1.89 hours per day in OFF time for patients with PD in comparison with placebo. These reductions were observed early as well, within the first week of treatment.4
The trial featured 128 patients with PD, 106 of whom were included in the final analysis, who were randomly assigned to 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. At the conclusion of the final follow-up, those on active treatment experienced 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 placebo (95% CI, –3.16 to –0.62; P = .0025).
Earlier this year, at the 2nd Annual Advanced Therapeutics in Movement and Related Disorders Congress, an expert roundtable of movement disorder specialists and dermatologists produced a protocol for skin nodules associated with 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.
Ultimately, the group noted that the majority of these nodules can be managed conservatively, with the panel suggesting that patients report any infusion-site reactions that do not improve, expand, or are associated with systemic symptoms to their clinicians. As infections are uncommon in the instance of infusion-site reactions/nodules, the group suggested that empiric antibiotics “were not felt to be necessary in most circumstances."5