Citing insufficient safety evidence for one of the drug’s main ingredients, the regulator in a Complete Response Letter rejected the company’s application for Parkinson’s disease candidate IPX203.
Pictured: FDA sign at its headquarters in Maryland/iStock, hapabapa
The FDA has denied Amneal Pharmaceuticals’ application for IPX203, its investigational extended-release carbidopa/levodopa capsules, which was being proposed as a treatment for Parkinson’s disease, the company announced Monday.
In its Complete Response Letter, the regulator said that while the New Jersey pharma was able to adequately establish the safety of levodopa—one of IPX203’s main ingredients—it had not sufficiently done so for carbidopa. The FDA has requested additional safety data for carbidopa and Amneal plans to meet with the agency to determine what the best path forward is for IPX203.
The regulator did not find problems with the candidate’s efficacy and manufacturing.
IPX203 is a novel oral formulation of carbidopa/levodopa (CD/LD), which is a well-established drug combination used for the management of Parkinson’s disease. When ingested, levodopa is metabolized into the neurochemical dopamine, which in turn helps improve motor symptoms and coordination that are typically impaired in Parkinson’s patients.
Carbidopa, meanwhile, promotes the absorption of levodopa into the central nervous system and helps minimize associated side effects such as nausea.
Amneal’s candidate uses immediate-release granules of both carbidopa and levodopa, while combining these with extended-release beads carrying only levodopa. In the Phase III RISE-PD trial, which the company used to support its regulatory bid, the extended-release treatment approach led to significantly better “good on” time, which refers to the total time without dyskinesia, even when dosed less frequently than an active control.
RISE-PD was a multi-center, randomized, and double-blinded trial that compared IPX203 against an immediate-release regimen. The study also showed that the extended-release treatment schedule resulted in significantly less “off” time, which is defined as periods in between doses when motor and non-motor symptoms emerge.
Monday’s rejection will not affect Amneal’s financial guidance for 2023, according to the company’s press release.
Amneal’s IPX203 is just one of many novel formulations of CD/LD in development. In January 2023, Phase III data showed that Mitsubishi Tanabe Pharma Corporation’s subcutaneous ND0612 led to significantly better “good on” time relative to oral formulations. Mitsubishi Tanabe’s candidate likewise improved “off” time and motor symptoms.
In March 2023, AbbVie’s own oral CD/LD formulation ABBV-951 (foscarbidopa/foslevodopa) also failed to pass the FDA’s regulatory rigor. In its rejection letter, the regulator requested for more data about the candidate’s accompanying device but did not cite problems with its evidence of efficacy and safety.
Like Amneal, AbbVie is working with the FDA to find the best way forward for ABBV-951.
Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
