Nancy is grateful for her opportunity at Myrtelle, to help bring innovative therapies to patients with serious, incapacitating, and life-threatening genetic disorders.

Nancy joined Myrtelle at its inception in 2021 and brings more than 25 years of experience in drug development. Nancy most recently served as Vice President, Head of Regulatory Affairs at Aruvant Sciences where she led the company in European Medicines Agency (EMA) Scientific Advice, development of the Pediatric Investigation Plan, and in obtaining EMA Orphan Drug and PRIME designation for ARU-1801, a lentiviral gene therapy for sickle cell disease. Previously, as Vice President of Regulatory Affairs at Agilis/PTC, Nancy developed gene therapies for rare neurological diseases including AADC deficiency (Upstaza), Friedreich Ataxia and Angelman Syndrome. Also, at Avexis, Nancy worked on the development of Zolgensma, a gene therapy for the rare disease Spinal Muscular Atrophy.


Q: Can you explain the regulatory path for an experimental drug like Myrtelle’s rAAV-Olig001-ASPA to become an approved treatment?

A: The fundamental goal of drug development is to establish efficacy and safety for the intended treatment in order to make an informed decision on the benefits versus the risks of the therapy. Considerations for health authorities such as FDA in drug approval include the overall number of patients who have been exposed to the therapy, the safety findings related to the drug and its administration, the availability of approved treatment options for the patients, and the test results that correspond to positive functional outcomes in patients.

Most gene therapies are intended to provide long-term, clinically meaningful benefits that correct the underlying genetic defect and either stop or reverse disease progression. That is Myrtelle’s goal for rAAV-Olig001-ASPA in Canavan disease patients.

Q: Why are the different phases of trials important and what moves a drug from trial to treatment?

A: One of the first steps in drug development is to conduct animal studies to understand whether the therapy could work, the overall safety and the starting dose for the first-in-human clinical trial. This step has been completed for rAAV-Olig001-ASPA.

Most standard development begins with a clinical study in healthy adult patients, but that is not usually the case for gene therapy. Because of the devastating nature of Canavan disease and the commitment involved in administration of gene therapy, our first-in-human studies have begun (Phase 1/2) and will continue with actual Canavan patients and will not use either healthy volunteers for initial assessments or a placebo arm for comparison (sham treatment). Patients treated with rAAV-Olig001-ASPA will be compared to historical records of disease progression in Canavan patients who were unable to receive the therapy in the past. The later phase is registrational (sometimes called Phase 3). A robust database will be built from the Clinical trials and then presented to health authorities for final drug approval and availability on the market for all
eligible patients with Canavan disease.

Q: FDA grants designations to drugs that aim to treat rare disease patients.  Can you explain the different designations and why they are important?

A: FDA provides a number of incentives to sponsors of rare disease research and drug development in order to stimulate the development of drugs for rare disease patients with unmet medical needs, and for whom there are few, if any, treatments.

FDA Orphan Designation means that the prevalence of the disease in the United States is fewer than 200,000 total patients. In addition, an orphan drug must show promise to treat, diagnose or prevent a disease. Upon approval of an orphan designated drug, FDA will grant the drug 7 years (instead of the usual 5 years) of marketing exclusivity, which means a generic drug cannot be marketed for the same purpose. Also, the sponsor will receive some tax credits for research costs and the new drug application will not require the usual FDA application fees.

Another incentive program from FDA is the Rare Pediatric Disease Designation (RPDD). In addition to the rare disease requirements for Orphan Designation, as the name implies, this program is designed to encourage drug development for children (birth to age 18). Also, the disease being studied must be serious or life-threatening. The specific incentives associated with this designation are eligibility for FDA “Priority Review” (6 months) and upon approval of the drug, a company will receive a voucher for a future priority review of another drug. This voucher is valuable to sponsors in that it can speed FDA approval of other drugs in development and can even be transferred (sold) to another sponsor.

Other means of expediting drug development and FDA review of new drug applications include the Fast-track designation which was recently granted to rAAV-Olig001-ASPA. Fast-track is not specifically for rare disease or for pediatric diseases and indicates that FDA agrees the drug under development, even if not yet studied in humans, is intended to treat a serious condition and has the potential to address an unmet need. This designation allows increased opportunity for consultation with FDA during development and can also help speed review of a new drug application. The next step in this “expedited” FDA process would be to seek Regenerative Medicine Advanced Therapy Designation for rAAV-Olig001-ASPA after more data is available from the clinical studies. This designation can also speed development and may even provide opportunities for early “accelerated” approval if evidence is appropriate.

In conclusion, each of these designation incentives ultimately benefits, in the case of rAAV-Olig001-ASPA, patients with Canavan disease by providing the therapy to address their unmet need and bringing it more quickly to the broader patient population who were not participants in the research. The designations are also especially helpful to a smaller company sponsor, normally expected to have relatively limited resources.

Q: What is the process for getting a drug registered around the world?

A: Each country or region has their own specific requirements for approval. For example, in the US new drug applications are made and reviewed by the Food and Drug Administration (FDA) and in Europe the application will be submitted to the European Medicines Agency (EMA). There is a separate application in each region or country as required by local regulation. Major countries and regions abide by the International Conference for Harmonization (ICH), which provides guidelines for all aspects of drug development from early phases through to approval and beyond. Included in ICH guidelines are ethical principles and scientific standards to which all manufacturing, nonclinical laboratories and clinical study centers must adhere. For example, in human research we have the principles of “Good Clinical Practice” (GCP), which contain specific research guidelines.

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