FDA issues second ABBV-951 rejection for Parkinson’s motor… – Parkinson’s News Today

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

In a complete response letter to AbbVie, the FDA said the decision is based on observations from an inspection at one of the companys third-party manufacturing facilities, although the inspection didnt 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 applicationin 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 Parkinsons 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.

Parkinsons 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. Its often combined with carbidopa, a medication that prevents levodopa from being converted to dopamine before it reaches the brain where its needed.

As Parkinsons 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.

ABBV-951 contains foslevodopa and foscarbidopa, inactive molecules that are metabolized into levodopa and carbidopa once inside the body, and also known as prodrugs. Its 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. Its anticipated to minimize troublesome motor fluctuations.

ABBV-951 is expected to be as effective as AbbViesDuopa, a carbidopa/levodopa intestinal gel thats used to control motor fluctuations in advanced Parkinsons. Duopa requires surgery to insert the delivery tube into the intestines, while surgery isnt needed for ABBV-951.

Regulatory applications to the FDA were backed by data from aPhase 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 Parkinsons in 34 countries worldwide, including Canada, where its sold as Vyalev, the European Union, and the U.K., where its sold as Produodopa.

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

The rest is here:
FDA issues second ABBV-951 rejection for Parkinson's motor... - Parkinson's News Today