Amneal Seeks Approval of IPX-203 in US to Boost Patient ‘Good On’ Time

Extended-release formulation of carbidopa-levodopa can work with fewer doses

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Amneal Pharmaceuticals is seeking U.S. approval of IPX-203, its extended-release carbidopa-levodopa (CD/LD) tablets, for Parkinson’s disease.

The company submitted an Investigational New Drug Application to the Food and Drug Administration (FDA), which is based on top-line data from the Phase 3 RISE-PD clinical trial that showed IPX-203 led to more “Good On” time — when CD/LD is working well and symptoms are controlled — compared to immediate-release tablets of the medication.

This was seen even when IPX-203 was taken three times per day, on average, compared to immediate-release tablets taken five times per day.

A post-hoc analysis revealed that IPX-203 increased “Good On” time by about 1.5 hours a dose, on average, compared to the immediate-release formulation. This represents a 70% increase per dose.

“The RISE-PD data indicate IPX203 can offer patients a new and important treatment option that will enable them to have more “Good On” time during the day, which we believe would be a significant new benefit for Parkinson’s patients,” Chintu Patel, co-CEO at Amneal, said in a press release. “We are working with the FDA to bring this treatment to market.”

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Parkinson’s is caused by the loss of neurons, or nerve cells, that produce the neurotransmitter dopamine — a chemical messenger essential for muscle control.

Levodopa is one of the mainstays of Parkinson’s treatment. It increases the brain levels of dopamine by delivering its precursor to cells. It can be used alone or in combination with carbidopa, an agent that helps prevent levodopa breakdown. As such, more of levodopa is available to make dopamine, reducing the amount of medication needed to be administered and, consequently, side effects.

However, while CD/LD therapy can ease Parkinson’s symptoms, it often becomes less effective over time, with patients developing “off” periods, when symptoms reappear between doses.

IPX-203 is a new version of extended-release CD/LD capsules designed to cause a quick rise in levodopa levels, followed by steady concentrations that extend beyond currently available products. This is expected to reduce “off” time.

RISE-PD trial found IPX-203 led to more hours of ‘Good On’ time per dose

The Phase 3 RISE-PD trial (NCT03670953) enrolled 506 adults, 40 and older, with advanced Parkinson’s. In the first three weeks, participants underwent dose-adjusting treatment with immediate-release CD/LD. This was followed by four weeks with IPX-203. Participants then were randomized to receive IPX-203 or standard immediate-release CD/LD for 13 weeks.

The trial’s main goal was to assess changes at the end of the study (week 20) in “Good On” hours per day, defined as the sum of “on” time without uncontrollable involuntary movements (dyskinesia) and “on” time with non-troublesome dyskinesia.

Secondary goals included changes in “off” time in hours per day and the proportion of patients who were “much improved” or “very much improved” according to the Patient Global Impression of Change — which reflects a patient’s beliefs about a treatment’s efficacy.

Changes in Parkinson’s motor symptoms and overall symptoms, measured by the Movement Disorder Society – Unified Parkinson’s Disease Rating Scale, were also assessed.

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Results showed that, compared to the immediate-release version, IPX-203 led to 0.53 more hours, on average, of “good on” time per day and reduced “off” time by about 0.48 hours per day on average.

Based on clinician assessments, 29.7% of participants treated with IPX-203 were “much improved” or “very much improved” in terms of overall health, compared to 18.8% of those given immediate-release CD/LD.

“We are very pleased to submit our [New Drug Application] for IPX203,” Chirag Patel, Amneal’s other co-CEO, said. “As leaders in the [Parkinson’s disease] space, Amneal knows how important it is for patients to achieve more ‘Good On’ time and live each day the way they choose. We are confident IPX203 can help them accomplish that goal.”