With the recent emergency authorizations of the Pfizer-BioNTech COVID-19 vaccine by the regulatory authorities in the United Kingdom, Canada, and United States (after a positive FDA advisory committee meeting on December 10, 2020), and with FDA holding a second advisory committee meeting to review the Moderna vaccine on December 17, 2020, we are on the verge of a significant breakthrough in coping with the COVID-19 global pandemic. Assuming FDA grants an emergency use authorization for the Moderna vaccine in addition to the authorization for the Pfizer-BioNTech vaccine, both will gradually become available in the United States over the next several months to vaccinate high-priority workers and high-risk individuals.

But it will still take some time for the vaccines to be available in sufficient quantities for everyone in the US who wants to be vaccinated, perhaps as late as mid-summer 2021. And with the current rate of infection (over 200,000 new infections each day in the US), in the immediate term there is still a tremendous need for affordable and accessible non-vaccine therapies to treat COVID-19, as well as for the long term to treat those who remain unvaccinated and/or still contract the virus. As a result, FDA’s continued support for development of such therapies through the Coronavirus Treatment Acceleration Program (CTAP) is absolutely critical.

FDA’s CTAP website continues to provide updated information and guidance for sponsors, including a dashboard reflecting the current development of potential COVID-19 therapies. As of November 30, 2020, there are more than 590 drug development programs in the active pre-IND planning stages and more than 390 clinical trials for non-vaccine therapies that FDA has reviewed and deemed safe to proceed. The types of COVID-19 treatments that sponsors are studying include antivirals, cell and gene therapies, immunomodulators, and neutralizing antibodies, as well as other products outside of these categories and combination products.

Although there is a great deal of activity on the part of sponsors trying to move potential therapies forward, as noted above, the majority of development programs are still in the pre-IND stage and are not yet ready for clinical trials. The good news is that there are over 300 late-stage clinical trials in progress in the US (trials testing efficacy and safety to determine whether the treatment is effective) for potential COVID-19 therapies. But to gain approval, sponsors must still meet appropriate requirements demonstrating safety and efficacy in COVID-19 patients, and to date, FDA has approved only one non-vaccine therapy, the antiviral drug Veklury (remdesivir), for the treatment of COVID-19 requiring hospitalization. FDA has granted emergency use authorization to 8 non-vaccine COVID-19 treatments, including casirivimab and imdevimab; baricitinib (Olumiant) in combination with remdesivir (Veklury); bamlanivimab; Veklury (remdesivir); and convalescent plasma.

For a sponsor who wants to develop a new COVID-19 therapy, the pre-IND pathway to engage FDA is still the appropriate approach, as described in Rho’s previous blog post on COVID-19 treatment development and discussed in a webinar earlier this year on Potential COVID-19 Products: Choosing the Right Path with FDA. Rho also previously summarized FDA’s guidance on Statistical Considerations for Clinical Trials During the COVID-19 Public Health Emergency and provided examples of activities Rho has undertaken to maintain trial integrity and patient safety in ongoing and upcoming clinical trials.

FDA continues to provide new and updated guidance related to development of COVID-19 therapeutics. Some notable ones include the following:

• Updates to the “Conduct of Clinical Trials of Medical Product During COVID-19 Public Health Emergency” that include new questions and answers regarding disposal of unused investigational product when a study participant cannot return it to the site, with alternatives that do not expose humans to the risks of the IP (December 4, 2020).
• A new infographic on the path for a COVID-19 Vaccine from Research to Emergency Use Authorization, explaining potential pathways (November 23, 2020).
• Finalization of the Guidance “Enhancing the Diversity of Clinical Trial Populations -Eligibility Criteria, Enrollment Practices, and Trial Designs,” an important consideration for COVID-19 treatments and any other treatment, in acknowledgement of health disparities and how adjustments to clinical study conduct could facilitate improvement in representation in clinical trials (November 2020).
• Finalization of the Guidance “Assessing COVID-19-Related Symptoms in Outpatient Adult and Adolescent Subjects in Clinical Trials of Drugs and Biological Products for COVID-19 Prevention or Treatment,” which includes discussion of measurement and analysis of COVID-19-related symptoms in these types of trials, including recommendations regarding patient-reported outcome instruments; a sample COVID-19-related symptom assessment; endpoint selection; and data handling considerations (September 2020).

Dr. Kevin Barber, PhD, RAC, PMP, Vice President of Regulatory Strategy & Submissions, has more than 20 years of experience in regulatory affairs and product development, working for both sponsor companies and CROs, across all stages of development from pre-clinical through product launch and post-approval life cycle management. He has led the preparation and execution of integrated regulatory strategy and clinical development plans for drug, biologic, and medical device products in therapeutic areas including dermatology, nephrology, urology, women’s health, CNS/neurology, cardiovascular diseases, virology, oncology, immunology, infectious diseases, blood products, and gene therapy. Dr. Barber has significant experience preparing and filing regulatory submissions, including more than 45 US INDs and more than 40 marketing applications in the US, Canada, Europe, Latin America, Australia, and New Zealand. He also has experience with medical device and in vitro diagnostic development programs and regulatory submissions including pre-IDE meetings, IDEs, 510(k)s, and PMAs.

Dr. Monica Frazier, PhD, RAC, Research Scientist, leads and contributes to multiple integrated product development programs at Rho, where she has experience in management of regulatory submissions at multiple stages of product development (INDs, NDAs, etc.) as well as in development of clinical documents to support clinical studies and regulatory submissions. She has over fourteen years of research; scientific and regulatory writing; and project management experience. Her experience includes leading and managing scientific authoring and editing teams, as well as preparing modules of regulatory submissions; briefing packages to support regulatory meetings; clinical study protocols; and clinical study reports.

Dr. Theresa Zucchero Scocca, PhD, RAC, Research Scientist, manages and contributes to multiple integrated product development programs at Rho and has over 18 years of experience in research, scientific and regulatory writing, and project management. In addition to leading programs ranging from the preclinical through the marketing application stages, her experience includes authorship of multiple regulatory and clinical documents, including draft product labels, briefing packages, protocols, clinical study reports, and marketing application modules such as the Clinical Overview and integrated summaries of safety and efficacy. She has also participated in multiple FDA meetings at various stages of development. Her management and regulatory authorship experience spans drug, biologic, medical device, and combination products and a broad range of therapeutic areas, including CNS, infectious disease, gastrointestinal diseases, osteoarthritis, analgesia, asthma, dental products, ADHD, inner ear disorders, and ophthalmology.