FDA Rejects Amneal’s Application for Novel Parkinson’s Therapy

The FDA has issued a complete response letter (CRL) for Amneal’s new drug application (NDA) for IPX203 for the treatment of Parkinson’s disease. The FDA is asking for additional pharmacokinetic data of carbidopa, one of the drugs in IPX203. Pharmacokinetic data provides information about how the drug is adsorbed, distributed, metabolized and excreted from the body.

Parkinson’s disease has become the fastest growing neurological disorder worldwide, with about 1 million patients diagnosed in United States. It is a progressive disorder of the central nervous system that affects dopamine-producing neurons in the brain that affect movement.

IPX203 is an oral formulation of carbidopa/levodopa extended-release capsules. The product contains extended-release beads that consist of levodopa, coated with a sustained release polymer, to allow for slow release of the drug. Additionally, this formulation contains immediate-release granules that consist of carbidopa and levodopa, with a disintegrant polymer to allow for rapid dissolution. The formulation of IPX203 is different from Rytary extended-release capsules, Amneal’s extended-release carbidopa/levodopa treatment for Parkinson’s disease that approved by the FDA in 2015.

The FDA’s CRL for IPX203 indicated that although an adequate scientific bridge was established for the safety of one ingredient, levodopa, based on pharmacokinetic studies, it was not adequately established for the other ingredient, carbidopa (CD), and FDA has requested additional information. The letter did not identify any issues with respect to the efficacy or manufacturing of IPX203.

Chintu Patel

Chirag Patel

“We are committed to advancing IPX203 for Parkinson’s disease, which has been developed to provide a longer duration of therapeutic benefit than existing formulations with fewer doses,” said Chirag and Chintu Patel, co-chief executive officers at Amneal said in a press release. “We plan to work closely with the FDA to address the agency’s feedback and we remain confident in bringing this new treatment to Parkinson’s patients as soon as possible.”

The NDA submission is based on the results from the phase 3 RISE-PD clinical trial, which found that IPX203’s extended-release formulation offers significantly more “Good On” time. The trial also showed this was the case when IPX203 was dosed on average three times per day and immediate-release carbidopa/levodopa was dosed on average five times per day. The trial also showed that subjects on IPX203 demonstrated significantly less “Off” time compared with immediate-release carbidopa/levodopa.

Many people living with Parkinson’s disease experience motor fluctuations as part of their symptoms. “On” time refers to periods when these symptoms are better controlled, and patients can move and function better. Carbidopa/levodopa has been used since the 1970s but additional options are needed to help patients function more consistently.