AbbVie Submits New Drug Application to U.S. FDA for Investigational ABBV-951 (Foscarbidopa/Foslevodopa) for the Treatment of Advanced Parkinson's Disease

• If approved, ABBV-951 will offer patients the first continuous subcutaneous delivery of carbidopa/levodopa prodrugs
• Submission is supported by Phase 3 study that demonstrated patients had significant increases in hours of "On" time without troublesome dyskinesia, compared to oral immediate-release carbidopa/levodopa

NORTH CHICAGO, Ill., May 20, 2022 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for ABBV-951 (foscarbidopa/foslevodopa) for the treatment of motor fluctuations in patients with advanced Parkinson's disease (PD).

The submission is based on results from a Phase 3, head-to-head, randomized and controlled clinical trial demonstrating statistically significant improvement in "On" time without troublesome dyskinesia compared to oral immediate-release carbidopa/levodopa (CD/LD).

ABBV-951 is designed to provide a first-of-its-kind, 24-hour, continuous subcutaneous delivery of CD/LD. Compared to oral CD/LD, it offers the potential for improvement in motor fluctuations in patients with advanced Parkinson's disease, a progressive and chronic neurological disorder resulting from the loss of dopamine-producing brain cells,¹ which primarily manifests with tremor, muscle rigidity, slowness of movement and difficulty with balance. In PD, patients and their healthcare providers share the same goal: to extend the amount of "On" time, referring to the period when symptoms are well controlled without dyskinesia or involuntary movements.

"Advanced Parkinson's disease causes unrelenting challenges and uncertainty for patients and caregivers worldwide," said Thomas Hudson, M.D., senior vice president, research and development, chief scientific officer, AbbVie. "We are committed to addressing the unmet needs of those affected by the disease and recognize the urgency for a new treatment that can enable better symptom control through the continuous 24-hour administration of medication."

The NDA is based primarily on data from the M15-736 study, a Phase 3 randomized, double-blind, double-dummy, active-controlled study, which demonstrated statistically superior efficacy of ABBV-951 compared to oral immediate-release CD/LD in controlling motor fluctuations in advanced PD patients.² Approximately 130 adult participants with PD, whose motor symptoms were no longer adequately controlled by their current medications, were enrolled in the study across 80 sites in the U.S. and Australia.

The majority of adverse events (AEs) were non-serious and mild or moderate in severity in the ABBV-951 group. There was one patient with a treatment-emergent AE leading to death in the oral CD/LD group and none in the ABBV-951 group. The most common AEs reported in ≥ 10% patients in the ABBV-951 group were infusion site AEs (erythema, pain, cellulitis and edema) and dyskinesia. The submission is also supported by results from an ongoing multi-center, Phase 3, 52-week, single arm, open-label study (M15-741), which is assessing the long-term safety and efficacy of ABBV-951.

AbbVie will continue to pursue regulatory submissions for ABBV-951 across international markets throughout the year.

About ABBV-951
ABBV-951 (foscarbidopa/foslevodopa) is a solution of carbidopa and levodopa prodrugs for continuous subcutaneous delivery that is being investigated for the treatment of motor fluctuations in patients with advanced Parkinson's disease.

About the Phase 3 M15-736 Study³ 
The Phase 3 randomized, double-blind, double-dummy, active-controlled study compared the efficacy, safety and tolerability of ABBV-951 (foscarbidopa/foslevodopa) to oral immediate-release CD/LD in patients with advanced PD. Participants were provided with a home diary (the PD Diary) to assess their motor state during the day. The primary endpoint of good "On" time (defined as "On" time without dyskinesia plus "On" time with non-troublesome dyskinesia), was collected and averaged over three consecutive days and normalized to a typical 16-hour waking period. Baseline values are defined as the average of normalized good "On" time collected over the three PD Diary days before randomization. Approximately 130 adult participants with advanced PD were enrolled in the study across 80 sites in the U.S. and Australia. Participants were randomized 1:1 to receive either the ABBV-951 solution as a continuous delivery under the skin (subcutaneous) plus oral placebo capsules for carbidopa/levodopa or oral capsules containing immediate-release carbidopa/levodopa plus continuous subcutaneous delivery of placebo solution for ABBV-951. The treatment duration was 12 weeks. More information on the study can be found on www.clinicaltrials.gov (NCT04380142).

About Parkinson's Disease
More than 10 million people worldwide are living with Parkinson's disease (PD)⁴, a progressive and chronic neurological disorder characterized by tremor, muscle rigidity, slowness of movement, and difficulty with balance.¹ The motor symptoms of PD result from the loss of dopamine-producing brain cells and begin when approximately 60-80 percent of these cells are lost.⁵ Symptoms continue to worsen slowly over the course of time.⁶ While there is no known cure for the disease, there are treatments available to help reduce symptoms.⁷

As PD progresses, patients experience motor complications, including motor and non-motor fluctuations and dyskinesia. Patients report switching from an "On" state (when symptoms are generally well controlled) to an "Off" state, during which symptoms such as tremor and stiffness may reappear and patients have more difficulty in moving.⁸ Patients with advanced PD may also experience dyskinesia (involuntary movements) which can significantly hinder daily activities.⁸ Neuronal degeneration and fluctuating plasma levodopa levels are responsible for the onset of these motor complications, with 50 percent of patients reporting them two to five years after diagnosis and approximately 80-100 percent of patients presenting with them after 10 years.⁹ 

About AbbVie in Neuroscience
At AbbVie, our commitment to preserve the personhood of those living with neurological and psychiatric disorders is unwavering. Every challenge in this uncharted territory makes us more determined and drives us harder to discover and deliver solutions for patients, care partners and clinicians. AbbVie's Neuroscience portfolio consists of approved therapies in neurological and psychiatric disorders, including bipolar I disorder, major depressive disorder, migraine, Parkinson's disease, post-stroke spasticity, schizophrenia, and others along with a robust pipeline.

We have a strong investment in neuroscience research, with our Foundational Neuroscience Center in Cambridge, Massachusetts, and our Neuroscience Discovery site in Ludwigshafen, Germany, where our research and resilience in these challenging therapeutic areas is yielding a deeper understanding of the pathophysiology of neurological and psychiatric disorders, and identifying targets for potential disease-modifying therapeutics aimed at making a difference in people's lives.

About AbbVie
AbbVie's mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women's health and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @AbbVie on Twitter, Facebook, Instagram, YouTube and LinkedIn  

Forward-Looking Statements
Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, failure to realize the expected benefits from AbbVie's acquisition of Allergan plc ("Allergan"), failure to promptly and effectively integrate Allergan's businesses, competition from other products, challenges to intellectual property, difficulties inherent in the research and development process, adverse litigation or government action, changes to laws and regulations applicable to our industry and the impact of public health outbreaks, epidemics or pandemics, such as COVID-19. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2021 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

References:
¹ About Parkinson's: Parkinson's 101. The Michael J. Fox Foundation for Parkinson's Research. Available at: https://www.michaeljfox.org/understanding-parkinsons/i-have-got-what.php#q2. Accessed March 1, 2022.
² AbbVie. Data on file.
³ Study Comparing Continuous Subcutaneous Infusion Of ABBV-951 With Oral Carbidopa/Levodopa Tablets For Treatment Of Motor Fluctuations in Adult Participants With Advanced Parkinson's Disease. ClinicalTrials.gov. 2021. Available at: https://www.clinicaltrials.gov/ct2/show/NCT04380142?term=NCT04380142&draw=2&rank=1. Accessed March 1, 2022.
⁴ Statistics. Parkinson's Foundation. Available at: https://www.parkinson.org/Understanding-Parkinsons/Statistics#:~:text=More%20than%2010%20million%20people. Accessed March 1, 2022.
⁵ Parkinson's Disease: Hope Through Research. National Institute of Neurological Disorders and Stroke. Available at: https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Hope-Through-Research/Parkinsons-Disease-Hope-Through-Research#:~:text=Loss%20of%20dopamine%20results%20in,by%20the%20time%20symptoms%20appear. Accessed March 1, 2022.
⁶ Parkinson's Disease: Challenges, Progress, and Promise. National Institute of Neurological Disorders and Stroke. Available at: https://www.ninds.nih.gov/Disorders/All-Disorders/Parkinsons-Disease-Challenges-Progress-and-Promise. Accessed March 1, 2022.
⁷ Parkinson's Disease. National Institute on Aging. Available at: https://www.nia.nih.gov/health/parkinsons-disease. Accessed March 1, 2022.
⁸ Wearing off and motor fluctuations. European Parkinson's Disease Association. Available at: https://www.epda.eu.com/about-parkinsons/symptoms/motor-symptoms/wearing-off-and-motor-fluctuations/. Accessed March 1, 2022.
⁹ Freitas ME, Hess CW, Fox SH. Motor Complications of Dopaminergic Medications in Parkinson's Disease. Semin Neurol. 2017;37(2):147-157. doi:10.1055/s-0037-1602423).

SOURCE AbbVie