Last updated May 11, 2023, by Lindsey Shapiro, PhD
Fact-checked by Marta Figueiredo, PhD
What is SPN-830 for Parkinson’s disease?
SPN-830 (apomorphine infusion device) is an experimental under-the-skin, or subcutaneous, continuous infusion therapy for reducing motor fluctuations that emerge between doses of standard levodopa-based treatment in people with Parkinson’s disease.
Supernus initially asked the U.S Food and Drug Administration (FDA) to approve SPN-830 in 2020, but the regulatory agency has twice requested additional information about the investigational therapy. However, the FDA does not require further clinical trials to test the treatment’s safety and effectiveness.
After meeting with the FDA in May 2023, the company announced it will resubmit its application by the end of 2023. The new revision process may take as long as six months, according to the FDA.
In Europe, a similar therapy has been available since the 90s for severe motor fluctuations. It is generally known as APO-go.
How does SPN-830 work in Parkinson’s disease?
Parkinson’s disease is caused by the progressive loss of nerve cells that produce dopamine, a brain signaling chemical.
Standard treatments include levodopa and related therapies that aim to increase dopamine levels in the brain. However, with long-term use, the effects of these treatments can wear off and symptoms may return between doses — the so-called off episodes.
SPN-830 is an under-the-skin formulation of apomorphine — a small molecule that mimics the effect of dopamine in the brain — that’s delivered continuously through a specialized infusion pump. As such, the therapy is expected to reduce off episodes in Parkinson’s patients.
This delivery method has the potential to be less invasive (fewer injection sites) and more convenient than Supernus’ Apokyn (apomorphine hydrochloride injection), an apomorphine subcutaneous injection that is approved for on-demand use to reduce off periods in Parkinson’s patients.
How will SPN-830 be administered in Parkinson’s disease?
In clinical trials, a 5 mg/mL solution of SPN-830 was continuously infused directly under the skin via a portable electronic infusion pump for a period of 14-18 hours. The target infusion rate ranged between 3 and 8 mg per hour. The very thin small needle that is applied underneath the skin is usually placed on the abdomen or upper thigh.
SPN-830 in Parkinson’s disease clinical trials
Supernus’ application to the FDA is based largely on data from two Phase 3 clinical trials.
The Phase 3 TOLEDO trial (NCT02006121) was the first placebo-controlled trial evaluating the safety and efficacy of apomorphine continuous subcutaneous infusion in Parkinson’s patients with off periods.
Sponsored by Britannia Pharmaceuticals, which markets APO-go, the Europe-based study enrolled 107 Parkinson’s patients, 30 and older, who were experiencing at least three hours daily of off time on an optimized levodopa-based treatment regimen.
Participants were randomly assigned to receive a continuous subcutaneous infusion of either an apomorphine solution (at a target rate of 3-8 mg per hour) or a placebo solution during waking hours (14-18 hours per day) over 12 weeks, or about three months. In both groups, the solution was delivered through the APO-go pump.
TOLEDO’s main goal was to determine the change in daily off time from the study’s start to the end of the treatment period, as assessed by patient symptom diaries.
Results showed that the continuous apomorphine treatment resulted in a significantly greater reduction in daily off time relative to a placebo (by 2.47 vs. 0.58 hours). Also, a greater proportion of apomorphine-treated patients experienced at least a 2-hour drop in daily off time compared with those in the placebo group (62% vs. 29%).
Consistently, daily good on time — when symptoms are adequately controlled without troublesome dyskinesia, or uncontrolled movements — was increased by 2.77 hours in the apomorphine group and by less than an hour in the placebo group. Dyskinesia is a common side effect of levodopa-based therapy.
Other outcome measures also favored the continuous subcutaneous apomorphine infusion, including greater reductions in levodopa doses and improvements in patient-reported outcomes. Moreover, the therapy was generally well-tolerated.
After completing the three-month placebo-controlled phase, 84 participants chose to enter the trial’s open-label extension phase, in which all received the apomorphine infusion for one year. Of them, 59 (70.2%) completed the study. Data showed that reductions in daily off time and increases in good on time were sustained through the extension phase.
The Phase 3 INFUS-ON trial (NCT02339064), sponsored by US WorldMeds, was designed to support the safety and efficacy findings of the TOLEDO study.
It enrolled 99 patients in the U.S. under similar enrollment criteria as TOLEDO and had a similar study design. The exception was that in INFUS-ON, all participants received the experimental therapy; there was no placebo group.
Results showed that three months of SPN-830 treatment led to a significant reduction in daily off time by a mean of three hours, and a three-hour mean increase in daily good on time. Also, 62.1% of patients experienced a 2-hour drop or more in daily off time.
Additional analyses showed that the therapy allowed patients to spend more than 80% of their waking hours in a good on state.
Common side effects of SPN-830
The most common side effects reported in SPN-830 clinical trials include:
- infusion site reactions like skin nodules and reddening
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