AbbVie’s 24-Hour Subcutaneous Infusion Therapy Approved by FDA for Parkinson’s Disease Treatment

On October 17th, AbbVie announced that the FDA has approved VYALEV (ABBV-951) as the first and only 24-hour continuous subcutaneous infusion therapy based on levodopa, intended to treat motor fluctuations in adult patients with advanced Parkinson’s disease (PD).

ABBV-951 is a prodrug of levodopa and carbidopa, with high water solubility, allowing continuous 24-hour subcutaneous infusion through a pump connected beneath the skin. This ensures stable concentrations of levodopa and carbidopa in the body for 24 hours, improving motor fluctuations in patients with advanced Parkinson’s disease.

Parkinson’s disease is an age-related neurodegenerative disorder characterized by the gradual loss of dopaminergic neurons in the substantia nigra, leading to motor symptoms such as bradykinesia, muscle rigidity, and resting tremors. Levodopa is the most widely used and effective medication for treating Parkinson’s disease. However, long-term use of levodopa medications in Parkinson’s patients can result in motor fluctuations, where symptoms unpredictably oscillate between improvement and worsening, unrelated to dosage or blood concentration, commonly referred to as the "on-off phenomenon" in clinical practice.

A prior Phase III head-to-head M15-736 study showed that subcutaneous administration of ABBV-951 significantly prolonged the "on" time (time without motor complications) in patients with advanced Parkinson’s disease compared to oral immediate-release levodopa/carbidopa (LD/CD). By week 12 of treatment, the "on" time increased by 2.72 hours in the ABBV-951 group, compared to a 0.97-hour increase in the oral LD/CD group (p=0.0083). Improvements in "on" time were observed as early as week 1 in the ABBV-951 group and were sustained through week 12.

Most adverse events in the ABBV-951 group were mild to moderate. One treatment-related death was reported in the oral LD/CD group, while no deaths occurred in the ABBV-951 group.

The approval journey for ABBV-951 has not been smooth. In March 2023, AbbVie received a Complete Response Letter (CRL) from the FDA, citing requirements related to the ABBV-951 device (the pump), requesting additional information to support the NDA. In June this year, AbbVie received another CRL from the FDA. At that time, AbbVie stated that the FDA listed results observed during an inspection of a third-party contract manufacturing organization, though this inspection did not involve ABBV-951 or its device. Moreover, the CRL did not identify any issues related to the safety, efficacy, or labeling of ABBV-951, and no additional efficacy and safety trials were requested.