FDA issues second rejection of ABBV-951 for motor fluctuations

Therapy is approved for treating advanced Parkinson's in 34 countries

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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The U.S. Food and Drug Administration (FDA) has rejected for the second time AbbVie’s application of ABBV-951 (foscarbidopa/foslevodopa) for treating motor fluctuations in adults with advanced Parkinson’s disease.

In a complete response letter to AbbVie, the FDA said the decision is based on observations from an inspection at one of the company’s third-party manufacturing facilities, although the inspection didn’t involve ABBV-951. No issues regarding the safety, efficacy, or labeling of ABBV-951 or its administration device were identified, and no additional clinical studies were requested.

The decision comes a little more than a year after the FDA first rejected the continuously infused medication. AbbVie submitted an application in 2022, which the agency rejected 10 months later, citing a need for more information about the specialized pump used to administer the treatment.

“There remains a tremendous unmet need for treatment options for patients living with advanced Parkinson’s disease in the United States,” Roopal Thakkar, MD, senior vice president and chief medical officer, global therapeutics at AbbVie, said in a company press release. “We are focused on working with the FDA to bring this important therapy to patients as soon as possible.”

Parkinson’s disease symptoms arise due to the progressive degeneration of nerve cells that produce dopamine, an important brain signaling chemical.

The gold-standard treatment is oral levodopa, a dopamine precursor, which is converted into dopamine in the body. It’s often combined with carbidopa, a medication that prevents levodopa from being converted to dopamine before it reaches the brain where it’s needed.

As Parkinson’s progresses, the response to levodopa may start to wane and patients have off episodes, or motor fluctuations, where motor symptoms return between doses. Moreover, oral levodopa can be partially metabolized in the gastrointestinal tract, leading to inconsistent levels of it in the brain.

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Duopa Found to Quickly Ease Motor Fluctuations in Phase 3 Trial

ABBV-951’s proposed effect on motor fluctuations

ABBV-951 contains foslevodopa and foscarbidopa, inactive molecules that are metabolized into levodopa and carbidopa once inside the body, and also known as prodrugs. It’s designed to be administered via continuous infusion under the skin, or subcutaneously, using a specialized delivery pump.

This mode of delivery allows for direct and rapid absorption into the bloodstream, enabling a more consistent levodopa/carbidopa dose to reach the brain. It’s anticipated to minimize troublesome motor fluctuations.

ABBV-951 is expected to be as effective as AbbVie’s Duopa, a carbidopa/levodopa intestinal gel that’s used to control motor fluctuations in advanced Parkinson’s. Duopa requires surgery to insert the delivery tube into the intestines, while surgery isn’t needed for ABBV-951.

Regulatory applications to the FDA were backed by data from a Phase 3 clinical trial (NCT04380142) that showed ABBV-951 was better than oral levodopa/carbidopa tablets for controlling motor fluctuations. Another  Phase 3 trial (NCT03781167) showed ABBV-951 was generally safe and well tolerated over a year of treatment, leading to reductions in daily off time and more time when symptoms were controlled.

The most common side effects of ABBV-951 include infusion site reactions, hallucinations, falls, anxiety, and depression.

ABBV-951 is approved for advanced Parkinson’s in 34 countries worldwide, including Canada, where it’s sold as Vyalev, the European Union, and the U.K., where it’s sold as Produodopa.

Mitsubishi Tanabe Pharma is developing a continuous subcutaneous infusion formulation of liquid levodopa/carbidopa called ND0612. The FDA also rejected its application this month.