AskBio Inc. (AskBio), a gene therapy company wholly owned and independently operated as a subsidiary of Bayer AG, today announced that investigational gene therapy AB-1005 for the treatment of Parkinson's disease (PD) has been granted Regenerative Medicine Advanced Therapy (RMAT) designation from the United States Food and Drug Administration (FDA).
"The FDA's decision to grant RMAT designation to AB-1005 is exciting news for people living with Parkinson’s disease and their loved ones," said Gustavo Pesquin, CEO, AskBio. "This milestone could potentially expedite the development of our important investigational gene therapy program, and it highlights our promising data and the potential of AB-1005 for patients and the medical community. We look forward to working closely with the FDA to accelerate our program."
The FDA determined that AB-1005, an investigational gene therapy intended to slow disease progression and improve motor outcomes in patients with PD, met the criteria for RMAT designation. This decision follows a review of information and data provided by AskBio, including clinical evidence from the open label, uncontrolled study Phase Ib trial of AB-1005.
AskBio's 36-month Phase Ib data showed that the administration of AB-1005 was well tolerated with no product-related serious adverse events.(1) Further, the moderate PD cohort showed trends for improvement or stability on several PD-relevant clinical scales at 36 months compared to baseline, including Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and self-reported PD motor diaries, together with trends in reductions in Parkinson’s medications (levodopa-equivalent daily dose [LEDD]).(1) Most participants in the mild PD cohort showed an overall stable clinical status with little change in MDS-UPDRS, the self-reported PD motor diary, or LEDD.(1)
RMAT is a designation granted by the FDA to regenerative therapies, including gene therapies, being developed to treat, modify, reverse, or cure serious or life-threatening diseases or conditions.(2) Investigational products receiving this designation must have produced preliminary clinical evidence indicating that they may have the potential to address unmet medical needs for such diseases or conditions.(2) RMAT provides recipients with enhanced access to the FDA, which could include intensive guidance on efficient drug development, rolling Biologics License Application (BLA) review, and other actions to expedite review.(2)
"The RMAT designation for AB-1005 underscores the high unmet medical need and the potential of this investigational gene therapy to make a difference for patients with Parkinson's disease," said Christian Rommel, Executive Vice President, Global Head of Research and Development and Member of the Pharmaceuticals Leadership Team at Bayer. "This is the latest example of what can be achieved through the joint commitment of AskBio and Bayer to deliver breakthrough innovation for patients."
The first participants in the AB-1005 Phase II REGENERATE-PD clinical trial have been randomized in the United States, and the trial is currently recruiting.(3) Additional study sites in the United States, Germany, Poland, and the United Kingdom are expected to be opened for enrollment in first half of 2025.(3)
AB-1005 has not been approved by any regulatory authority, and its efficacy and safety have not been fully established or evaluated.
About Parkinson's disease
Parkinson's disease (PD) is a progressive neurodegenerative disease. It has a significant impact on a person's daily life. In PD the death of dopamine producing nerve cells in the brain leads to the continuous loss of motor function.(4) Symptoms include tremors, muscle rigidity, and slowness of movement.(4) Additionally, people with PD experience non-motor symptoms, including fatigue and lack of energy, congestive issues, and depression.4 Symptoms typically intensify over time and make everyday tasks increasingly demanding.(4) The prevalence of PD has doubled over the past 25 years.(5) Today, more than 10 million people worldwide are estimated to be living with PD.(6) This makes it the world's second most prevalent neurodegenerative disease.(7) It is also the most frequent movement disorder.(8,9) At present there is no cure, and current treatment options lack the holistic management of symptoms, so new therapies are needed.(10,11)
About the AB-1005 Phase Ib trial
In this Phase Ib, multi-center, multi-site, open-label, uncontrolled trial, 11 patients were administered AB-1005 to the putamen via one-time bilateral convection-enhanced delivery. Patients were enrolled into two cohorts, mild (6 patients) and moderate (5 patients), based upon the duration and stage of their PD. The objective of this investigation was to evaluate the safety and potential clinical effect of AB-1005 delivered to the putamen in patients with early/mild or moderate PD. The outcomes assessed at 36 months were incidence of Treatment-Emergent Adverse Events (TEAEs) as reported by the patients or assessed clinically by physical and neurological examinations, motor symptoms as reported via the Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and PD Motor Diary self-assessments, non-motor symptoms of PD, and brain dopaminergic network integrity as measured by DaTSCAN.(1) These assessments will continue for up to five years. For more information, visit clinicaltrials.gov (NCT#04167540 or askbio.com).
About REGENERATE-PD
REGENERATE-PD is a Phase II, randomized, double-blind, sham-controlled trial of the efficacy and safety of intraputaminal AB-1005 in the treatment of adults (45-75 years) with moderate-stage Parkinson's disease. The trial will include an estimated 87 subjects with trial sites located in the United States, Germany, Poland, and the United Kingdom. For more information about the REGENERATE-PD clinical trial, visit clinicaltrials.gov (NCT06285643), or visit askbio.com.
About AB-1005
AB-1005 is an investigational gene therapy based on adeno-associated viral vector serotype 2 (AAV2) containing the human glial cell line-derived neurotrophic factor (GDNF) transgene, which allows for stable and continuous expression of GDNF in localized regions of the brain after direct neurosurgical injection with MRI-monitored convection enhanced delivery.(12) In nonclinical studies, GDNF has been shown to promote the survival and morphological differentiation of dopaminergic neurons.(13,14) Recombinant GDNF has long been evaluated as a potential treatment for diseases, such as Parkinson’s disease (PD), marked by progressive degeneration of midbrain dopaminergic neurons.(15) Through a combination of an investigational gene therapy and innovative neurosurgical delivery approach, we can now test the GDNF hypothesis in PD by getting this neurotrophic factor to these degenerating nigrostriatal neurons in a potentially more clinically relevant fashion.(15)
About AskBio
AskBio Inc., a wholly owned and independently operated subsidiary of Bayer AG, is a fully integrated gene therapy company dedicated to developing life-saving medicines and changing lives. The company maintains a portfolio of clinical programs across a range of neuromuscular, central nervous system, cardiovascular, and metabolic disease indications with a clinical-stage pipeline that includes investigational therapeutics for congestive heart failure, limb-girdle muscular dystrophy, multiple system atrophy, Parkinson’s disease, and Pompe disease. AskBio’s gene therapy platform includes Pro10™, an industry-leading proprietary cell line manufacturing process, and an extensive array of capsids and promoters. With global headquarters in Research Triangle Park, North Carolina, and European headquarters in Edinburgh, Scotland, the company has generated hundreds of proprietary capsids and promoters, several of which have entered pre-clinical and clinical testing. An early innovator in the gene therapy field, with over 900 employees in five countries, the company holds more than 600 patents and patent applications in areas such as AAV production and chimeric capsids.
About Bayer
Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, "Health for all, Hunger for none," the company's products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2023, the Group employed around 100,000 people and had sales of 47.6 billion euros. R&D expenses before special items amounted to 5.8 billion euros.
1. Nicolas M, et al. Preliminary Efficacy of GDNF Gene Therapy (AAV2-GDNF; AB-1005) in Parkinson’s Disease: 36-Month Follow-Up From a Phase 1b Study. Presented at the International Congress of Parkinson's Disease and Movement Disorders 2024.
2. Food and Drug Administration. Expedited Programs for Regenerative Medicine Therapies for Serious Conditions. Available at: https://www.fda.gov/media/120267/download. Accessed: February 2025.
3. AskBio.com. First participants randomized in AskBio Phase II gene therapy trial for Parkinson's disease. Available at: https://www.askbio.com/first-participants-randomized-in-askbio-phase-ii-gene-therapy-trial-for-parkinsons-disease/. Accessed: February 2025.
4. National Institutes of Health. Parkinson's Disease Available at: https://www.ninds.nih.gov/health-information/disorders/parkinsons-disease. Accessed: February 2025.
5. World Health Organization. Parkinson disease. Available at: https://www.who.int/news-room/fact-sheets/detail/parkinson-disease. Accessed: February 2025.
6. Parkinson's Foundation. Who has Parkinson's? Available Parkinson's Foundation. Who has Parkinson's? Available at: https://www.parkinson.org/understanding-parkinsons/statistics. Accessed: February 2025.
7. National Institute of Environmental Health Sciences. Neurodegenerative Diseases. Available at: https://www.niehs.nih.gov/research/supported/health/neurodegenerative. Accessed: February 2025.
8. World Health Organization. Parkinson disease. Available at: https://www.who.int/news-room/fact-sheets/detail/parkinson-disease. Accessed: February 2025.
9. Stoker TB, Barker RA. Recent developments in the treatment of Parkinson's Disease. 2020
10. Mayo Clinic. Parkinson's disease. Available at: https://www.mayoclinic.org/diseases-conditions/parkinsons-disease/diagnosis-treatment/drc-20376062. Accessed: February 2025.
11. Rizek P, An update on the diagnosis and treatment of Parkinson's disease. 2016.
12. Heiss JD, et al. Trial of magnetic resonance-guided putaminal gene therapy for advanced Parkinson's disease. Mov Disord. 2019 Jul;34(7):1073-1078.
13. Kells AP, et al. Regeneration of the MPTP-lesioned dopaminergic system after convection-enhanced delivery of AAV2-GDNF. J Neurosci. 2010 Jul 14;30(28):9567-77.
14. Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F. GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science. 1993;260(5111):1130-1132.
15. Barker RA, et al. GDNF and Parkinson's Disease: Where Next? A Summary from a Recent Workshop. J Parkinsons Dis. 2020;10(3):875-891.