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COVID-19 Treatment Development: Updates and Recent FDA Guidance

Posted by Theresa Scocca and Monica Frazier on Wed, May 27, 2020 @ 09:00 AM
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The FDA continues to release additional information and update their website as the COVID-19 pandemic continues and both regulatory professionals and drug developers react to the potential for novel and repurposed products to treat COVID-19. This blog post is the latest installment in a series of COVID-19 related blog posts and updates information provided in a recent webinar on Potential COVID-19 Products: Choosing the Right Path with FDA.

Recent changes to the Coronavirus Treatment Acceleration Program (CTAP) webpage have included additional details about how to proceed based on whether the product of interest will be reviewed by CDER or CBER (or if jurisdiction is undetermined). For products under the jurisdiction of CDER, submission of a package through typical channels is expected; sponsors of products under jurisdiction at CBER should contact their Division to confirm next steps. Of note, the Agency clarifies that medical devices are not part of CTAP and that sponsors of these products should contact CDRH directly communication regarding the development of IVDs and non-IVD medical devices.

In addition, two new guidance documents for COVID-19 treatment development have been released in May 2020. The first, COVID-19 Public Health Emergency: General Considerations for Pre-IND (Investigational New Drug application) Meeting Requests for COVID-19 Related Drugs and Biological Products, includes information on best practices for obtaining feedback from the Agency for streamlining the time to initiation of clinical trials for COVID-related drugs and biologics. The guidance specifically states that sponsors should initiate discussions regarding the development of COVID-19 treatments via the pre-IND pathway rather than through a pre-emergency use authorization (EUA) request as products are likely not ready to proceed directly to a successful EUA request. In addition, this guidance clarifies that despite the public health crisis due to the COVID-19 pandemic, a draft/brief study synopsis without a full meeting package to support a pre-IND meeting will likely be considered inadequate for review, and may result in a sponsor’s request not receiving prioritization with the Agency.

Details in the guidance include information on the type of data and information that sponsors should provide across functional areas (clinical, nonclinical, and quality) to support these meeting requests. Important to considerations for submitting a meeting request are that all relevant materials for FDA’s evaluation should be included with the request, including the meeting package, questions, and proposed clinical protocol. A summary of the data and literature supporting the proposed use of the drug for treatment or prevention of COVID-19 is expected. A detailed list of content that should be included in the package is provided.

Per the guidance, the sponsor should submit with the pre-IND meeting request a draft protocol that includes phase of development, mechanism of action, overall design, subject population with inclusion and exclusion criteria, endpoint(s), safety assessments, and brief statistical considerations. It should also include a detailed safety monitoring plan and detailed time and event table with end of trial and follow-up plans. A detailed list of all content that should be included in the package is provided.

The second new guidance, COVID-19: Developing Drugs and Biological Products for Treatment or Prevention, includes focused information on the design of studies in support of the development of drugs and biologics with direct antiviral activity or immunomodulatory activity. Considerations are provided related to study population, trial design, efficacy endpoints, safety considerations, and statistical considerations. In addition, an Appendix with examples of baseline severity categorization is provided to assist Sponsors in protocol development. This guidance will be essential to review in advance of and in parallel with clinical protocol development for COVID-19 products.

Rho supports Sponsors at all stages of product development, including but not limited to assistance navigating the ongoing development of regulatory guidance for COVID-19 products; development of protocols, meeting requests (including question formulation by functional experts), briefing packages, and meeting moderation and attendance; program management; submission support for all stages from pre-IND through marketing application; and full-service clinical study execution at all study phases, from project management, site management, and clinical monitoring, through data management and statistical analysis, to preparation of submission-ready reports to support marketing applications.

Theresa4-1Theresa 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.

Monica1Monica 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.

The Sunsetting of Rare Pediatric Disease Designation

Posted by Joseph Watson on Mon, May 18, 2020 @ 09:30 AM
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As with other incentive programs, FDA created the Rare Pediatric Disease (RPD) designation to encourage drug development in products with questionable financial viability; in this case, the treatment of certain rare pediatric diseases.  One of the main benefits of RPD designation is the potential to receive priority review vouchers, which can be used to obtain priority review on a subsequent human drug or biologic application, should the product with RPD designation be approved.  Priority review vouchers have few restrictions, and can be used by the sponsor or sold/transferred to a separate organization.  In some cases, priority review vouchers have sold for over $100 million.superhero-team

While the potential financial benefits of RPD designation are compelling, the program, as mandated by the 21st Century Cures Act, has limited availability.  As things currently stand, FDA is sunsetting the program, and may not award priority review vouchers for any product unless the product has received RPD designation by September 30, 2020.  Therefore, as of the time of this article, pharmaceutical companies have approximately 5 months to receive the designation from the Office of Orphan Products Development (OOPD) at FDA.  FDA does have a review clock on such an application, but only under specific circumstances.  Section 529(d)(2) provides that a sponsor shall submit a request for RPD designation at the same time that they submit either an orphan drug application or a fast track designation; FDA has interpreted “at the same time” to mean within 2 weeks.  If a timely submission occurs, then section 529(d)(3) directs FDA to make a decision on the request no later than 60 days after the submission.  Note that, if the application is submitted in a timely fashion, information in an orphan drug application can be cross-referenced rather than transferred into the RPD application itself.  If submitted outside of a request for orphan drug or fast track designation, then FDA is under no time frame for review.

How can a sponsor increase the chances of a favorable first round review?  The first step is to ensure that the proposed indication meets the requirements for orphan designation, as the RPD application itself requests very similar information.  Second, we recommend that sponsors include data from the literature to support the early and serious effects of the disease in children.  Seriousness of the disease in childhood is critical to approval, and providing solid evidence from the literature or other data sources to substantiate this claim is the most important element that is needed for the RPD designation request beyond what one would provide for an orphan designation request.  Based on our previous experience, this means showcasing to the OOPD that greater than greater than 50% of the affected population in the US is between birth and 18 years of age.  This can generally be achieved by summarizing prevalence of serious symptoms by age. 

Finally, even if a sponsor’s product receives RPD designation, the guidance notes that, after September 30, 2022, FDA may not award any RPD priority review vouchers.  While this may cause some sponsors to hesitate, especially if their product is early in development, we note that legislative extensions can occur, and therefore seeking RPD designation may still be valuable.  

In any case, Rho can help your company move forward with a timely RPD submission.  Please contact our business development group if you have any questions.

 Joseph1-1Joseph Watson, PhD, RAC, Research Scientist at Rho, has experience in both regulatory submissions and clinical document preparation, with over fifteen years of experience in scientific writing and editing clinical and nonclinical documents, including numerous publications in peer-reviewed journals.  Dr. Watson has led the preparation, review, and coordination of a variety of regulatory and clinical documents, including protocols; clinical study reports; integrated summaries of biopharmaceutics, safety, and efficacy; CMC and nonclinical documents; draft product labels; and 120‑day safety updates.  His writing and editing experience covers a broad range of therapeutic areas, including drug addiction, middle ear disorders, infectious diseases, psychiatric disorders, acute and chronic pain, multiple sclerosis, hemophilia, and oncology.