As part of WuXi AppTec’s ongoing efforts to collaboratively foster new thinking and actionable approaches in advancing breakthroughs for patients, we have launched a new interview series in 2022 – “Delivering on the Promise of New Modalities” – so leading voices of R&D can share how their approaches are addressing the barriers standing in the way of breakthroughs.

For our next interview in this series, Amber Van Laar joins us as VP Clinical Development, CNS Gene Therapy of Asklepios Biopharmaceutical (AskBio) to shed light on neurodegenerative disease drug development. AskBio is a company dedicated to develop AAV (adeno-associated virus) based gene therapies for neuromuscular, central nervous system, cardiovascular, metabolic and other disorders. Last year, the company received FDA fast track designation for a novel investigational gene therapy for the treatment of a rare muscular dystrophy with no approved therapies. AskBio is also most notably working on a gene therapy for Parkinson’s Disease, and a gene therapy treating late-onset Pompe disease.

One of the leading candidates of AskBio is focusing on Parkinson’s disease. From your perspective, why the treatment for Parkinson’s disease remains challenging?

Amber: That’s a good question. To me, non-motor symptoms of Parkinson’s disease such as cognitive impairment, constipation, and depression can be more troublesome to patients than the classical motor symptoms, like tremors or slowness of movement. However, effective symptom management is not adequately addressed by currently available therapies. Further development is needed, particularly for preventative therapies, to evade these complicating and troublesome disease features.

The lack of disease-modifying therapies remains a key challenge for patients and researchers, though many promising studies are underway. Close collaboration with regulatory agencies will be critical in order to establish a clear path to agreement on what measures are needed to define disease modification which are meaningful for both regulators and the Parkinson’s community.

What are the opportunities for novel technologies to solve these challenges? What’s AskBio’s unique approach?

Amber: The safe and accurate neurosurgical drug delivery directly to specific brain regions or neuronal networks has been rapidly evolving to overcome the pre-existing challenges of unmonitored “black box” administration of drugs intracranially.

Direct visualization via MRI-monitored drug delivery to the brain was a significant technological leap that now allows neurosurgeons to dose drugs directly, accurately and consistently in brain regions impacted by a particular disease.

At AskBio, our Parkinson’s program utilizes direct, MRI-guided delivery of AAV2-GDNF (glial cell-line derived neurotrophic factor) to evaluate the potential of this technology to overcome the challenges of variable delivery which may have contributed to the lack of significant responses observed in prior studies investigating either recombinant GDNF protein delivery or gene therapy approaches for Parkinson’s Disease. We believe that these improvements in delivery are crucial to accurately dose gene therapy to demonstrate a clinical effect, particularly for a neurotrophic growth factor like GDNF.

Great. As your platform evolves, how to realize its full potential? What are the key elements for success?

Amber: Delivering a new therapeutic platform at scale, particularly for the central nervous system and other disorders requiring specialized delivery, is a challenge on the horizon for cell and gene therapies.  The incorporation of robotic-assisted procedures, portable MRI scanners, and improved delivery devices will be needed to expedite procedures and reduce the resource intensiveness of the current procedure.

Alongside the evolution of the surgical procedure, the development of cell and gene therapy centers of excellence will be needed to adequately train and disseminate this new technology beyond a limited number of highly trained neurosurgeons at major academic centers.

Additionally, an early dialogue with payers and health agencies is needed for these advanced therapies to facilitate the post-approval path for one-time delivery of potential disease-modifying drugs. Aspects of neurosurgical delivery and the combined use of drug and novel devices further complicate this process, necessitating preemptive discussions with stakeholders to efficiently bring these novel therapies to patients.

How do you see the field of gene therapy evolve in the next 10 years? Will gene therapy become the mainstream of new drugs approved?

Amber: The approval path in the field of gene therapy has been embarked on by a few sponsors since 2015. The approval process of gene therapies is fraught with hurdles given the manufacturing requirements and the high bar these treatments are expected to achieve. The potential for one-time delivery of gene therapy and unknown long-term effects are additional factors that have prudently been raised as factors needed for the rigorous evaluation of gene therapies.

The number of new INDs for gene therapies has sharply risen over the past five years, attesting to the promise that this technology holds. Given lengthy drug development timelines, and challenges with diseases like neurodegenerative disorders, I believe many of these studies may not achieve approval by 2030.

This field is in its advent, and with only a few approval successes to provide guidance to subsequent studies. Learnings from future approvals will provide clarity on the rigorous gene therapy approval process for sponsors and regulators. As the regulatory path becomes more trodden, and with further refinement of this powerful technology, gene therapy is on course to open the door to a new modality of treating previously untreatable diseases.

Anything else that may evolve over time in your view as we look towards 2030?

Amber: The ability to reduce the cost of approvals in half by 2030 may be achievable in select drug development spaces. I believe these savings would not be anticipated for areas like cell and gene therapy. The novelty of cell and gene therapy and the potential of these therapies hold to change the direction of medicine are factors limiting cost and time savings in the early days of cell and gene therapy development. But I believe the utilization of decentralized trial designs, streamlined clinical development strategies, and the implementation of remote monitoring of participants in a real-world setting will hold the potential to reduce the overall costs of bringing drugs to approval.

Thank you so much for your time, really appreciate your insights.

Amber: My pleasure.

 

---

 

Amber D. Van Laar, MD

VP Clinical Development, CNS Gene Therapy, Asklepios Biopharmaceutical Inc. (AskBio)

Dr. Amber Van Laar obtained her MD from the University of Pittsburgh School of Medicine, followed by residency training in Neurology and a clinical-research fellowship in Movement Disorders at the University of Pittsburgh Medical Center. She later joined the department as an Assistant Professor in the Movement Disorders Division. As a physician-scientist, Dr. Van Laar continued her academic research in the Pittsburgh Institute for Neurodegenerative Diseases and received formal clinical research training through the Institute of Clinical Research Education at the University of Pittsburgh.

Since 2002, Dr. Van Laar has researched gene therapy approaches for Parkinson’s disease and received the Clinician-Scientist Development Award from the Parkinson’s Foundation and the American Academy of Neurology to investigate the therapeutic potential of parkin gene therapy in parkinsonian rodent models. Dr. Van Laar has also been an investigator in clinical trials for neurodegenerative diseases, including multiple gene therapy studies for Parkinson’s disease. 

Through volunteer work with local PD support groups and service on the Board of Directors for the Parkinson’s Foundation of Western Pennsylvania, she continues to contribute to the Parkinson’s disease community.

Dr. Van Laar continues her work with gene therapy and now serves as the VP of Clinical Development for CNS Gene Therapy at Asklepios BioPharmacetuical Inc. (AskBio). She brings a unique blend of preclinical, clinical, and clinical-trial development experience to the advancement of gene therapy as a new platform to address the underlying causes of Parkinson’s disease and similar brain diseases.