Facet Life Sciences Quarterly Update Q2 – 2023

ULTRA RARE DISEASE DEVELOPMENT:

Facet helps growing start-up design a development plan for a pediatric ultra rare disease indication.
A small ex-US company asked Facet to provide US regulatory affairs and strategic development guidance regarding their product for a predominately pediatric ultra rare disease.  Facet reviewed the nonclinical and CMC work done on the product to date and recommended 1 phase 1/2 trial in adult patients diagnosed with the disease and 1 phase 3 global trial, based on regulatory precedent.  Facet also helped the company select a target indication and trial endpoints.  The company is working with Facet to submit an orphan designation request and a rare pediatric disease designation request.

DEVELOPMENT PROGRESS WITH COST SAVINGS:

Facet helped a small pharmaceutical company save time and money.  A pre-IND stage start-up company asked Facet to help design a streamlined development program to help them to get to IND.  Facet noted that the company was spending a lot of time and money juggling many nonclinical CROs and boutique labs.  On Facet’s recommendation, the company consolidated the activities to a few strategic CROs enabling them to shave months off their development plan and avoid the need to seek an additional capital raise prior to IND submission.  If you are a small company who is trying to do more with less, click here to talk to a Facet regulatory expert about your program.

Dr. Jason Mercer attended the annual Food and Drug Law Institute (FDLI) annual conference May 17-18 in Washington, DC.  The FDLI annual conference addresses complex legal, regulatory, compliance, and policy issues faced by FDA-regulated industry.  The conference fosters in-depth discussions of timely topics in the industry by bringing together experts from the federal government, industry, law firms, patient and consumer advocacy groups, consulting organizations, and academia.  This year’s conference featured presentations on the FDA’s strategic priorities for the upcoming year from Dr. Robert Califf, FDA Commissioner and Mark Raza, FDA Chief Counsel.  In depth discussions highlighted recent congressional actions and recent court cases and the impacts on the FDA, industry, and public health.  Sessions on rare disease drug development, regulation of cell and gene therapies offered helpful insights into current industry and FDA approaches in these highly important and evolving areas of therapeutic product development.

Dr. Lisa VanLuvanee attended the FDA CDER & JHU CERSI Workshop:  Addressing Challenges in the Design and Analysis of Rare Disease Clinical Trials: Considerations and Tools on May 2-3. In this workshop, FDA and Johns Hopkins University’s Center for Excellence dynamically discussed the challenges of drug development for rare diseases.  Topics included clinical trial design and interpretation issues resulting from a small number of patients with individual disorders, the lack of drug development and regulatory precedent for many rare diseases, and the lack of established endpoints.  The pros and cons of real-world evidence (RWE), natural history studies, and registries were also noted.  The meeting recording, slides, and other information are provided via a link on FDA’s website here: https://www.fda.gov/drugs/news-events-human-drugs/fda-cder-jhu-cersi-workshop-addressing-challenges-design-and-analysis-rare-disease-clinical-trials

Dr. Lisa VanLuvanee attended the Duke-Margolis Center / FDA workshop on Rare Disease Endpoint Advancement: Novel Endpoints for Rare Disease Drug Development on June 7-8. The Duke-Margolis Center for Health Policy and FDA convened to discuss the challenges and opportunities in rare disease endpoint development.  Of specific interest, the Rare Disease Endpoint Advancement (RDEA) Pilot Program was highlighted.  The goal of the RDEA program is to foster more rapid rare disease product development through enhanced Sponsor-FDA collaborations on the efficacy endpoint development process.  The RDEA program is also intended to provide greater transparency of evolving science through FDA presentations, guidance documents, public workshops, and a public-facing website.  Although only 1 RDEA proposal request is being granted in 2023, FDA will accept up to 3 RDEA proposals each year for fiscal years 2024-2027.  Facet is excited to see the FDA’s efforts to collaborate with Sponsors on rare disease development and is optimistic for the future of product development in this space.  The meeting recording, slides, and other information are publicly available on Duke’s website here: https://healthpolicy.duke.edu/events/rare-disease-endpoint-advancement-pilot-program-workshop-novel-endpoints-rare-disease-drug

NEW FACET TEAM MEMBER. Facet welcomes Dr. Marcoita Gilbert, an accomplished regulatory professional with 10 years of technical expertise in nonclinical drug development and applied toxicology.  Marcoita has a Ph.D., in pharmacology, toxicology, and physiology from the Brody School of Medicine at East Carolina University.  She also holds 3 BS degrees (neuroscience, chemistry, and biology).  Prior to joining Facet, she served as a Director of Regulatory Affairs at Cardinal Health, and formerly held roles as an expert toxicologist at both Cato and Camargo.  We are excited to welcome Marcoita to the Facet team as a Product Development Champion!

• Facet helps to develop products in every therapeutic area and has specialty expertise in ophthalmology, oncology, diagnostic/therapeutic radiopharmaceuticals, and controlled substances
• Facet’s scientific experts can author any document in a regulatory submission for FDA.  We write submissions documents with the FDA reviewer in mind.
• Facet is a leading regulatory affairs and development partner in advancing products for rare and ultra rare disease indications
• Facet submits 12-15 INDs a year and 3-5 NDA/BLAs a year
• Facet team members attend FDA public meetings, FDA-Industry workshops, professional conferences, and working groups monthly to stay on the cutting edge of science, regulatory affairs, and product development

FDA issues important draft guidance for developers of psychedelic drugs for potential treatment of medical conditions (June 23, 2023).  Currently, there are hundreds of organizations across the world who are developing psychedelics for medical use.  Prior to the issuance of FDA’s draft guidance in June, these developers had little regulatory guidance beyond meeting with FDA on a product-by-product basis to understand how to progress their product through to FDA approval.  FDA’s June 2023 draft guidance is a relief to many Sponsors because it outlines FDA’s current thinking on nonclinical, CMC, and clinical topics for Sponsors who are developing psychedelic products.  The information on CMC is particularly helpful and outlines what is required to support an IND and an eventual NDA.  Despite popular belief, FDA’s expectation is that psychedelic drugs under investigation must be manufactured in compliance with GMP, even in Phase 1. With respect to nonclinical information, FDA’s expectation is that Sponsors will include information regarding the product’s pharmacological and toxicological properties that led the Sponsor to conclude that the product at the planned doses and treatment regimen would be safe in humans.  Further, the pharmacokinetic and/or pharmacodynamic profile of the product is expected to be adequately characterized in vitro and in vivo.  Sponsors should pay particular attention to evaluating drug-drug interactions and abuse potential.  Finally, FDA is clear that all drugs, including psychedelics, must adhere to the substantial effectiveness standard to establish the effectiveness of the product, although special design features need to be used to manage the unique nature of psychedelic drugs.  The guidance does an excellent job of describing how to handle the use of a placebo control, paired psychological support/psychotherapy, and subject, observer, and analyst bias).  If you are developing a psychedelic product for a medical use, see the guidance for more information or talk to Facet – we have worked with Sponsors and FDA to successfully progress psychedelic products through development.

FDA issues guidance on direct-to-consumer promotional labeling and advertisements (June 2023).  In this guidance, FDA provides a review of studies that have shown that comprehension of efficacy and risk-based material by consumers is more accurate and easily understood if comparisons between treatment and control groups are quantitative.  Citing one of FDA’s examples, “In a clinical trial, 78 out of 100 patients experienced a response after 12 weeks of treatment with Drug X, compared to 20 out of 100 patients on placebo.”  The guidance also summarizes how visual aids can help consumers understand quantitative efficacy and risk information and provides helpful suggestions on how to design such aids to align the information with the purpose and objective of the communication.  For more information, see FDA’s guidance here.

Important Upcoming Deadline – October 1, 2023:  All 510(k) submissions must be sent to FDA using the eSTAR template.  Currently, medical device Sponsors may submit their 510(k) using the traditional format or they may voluntarily use the eSTAR template, an interactive PDF that contains automation, content and structure that is complimentary to how FDA reviews and has guided construction for each written section.  We highly recommend all Sponsors use the eSTAR template voluntarily now because it streamlines the process and results in a more robust, complete submission.  However, all Sponsors must use the eSTAR template when submitting their medical device application starting October 1, 2023.

Total submissions to FDA April – June 2023:  35 (on average almost 3 submissions a week!)

Early-stage development highlights: preparation/submission of 3 new INDs and submitted over 22 IND amendments (e.g., new protocols/amendments, CMC updates, nonclinical study reports, annual reports, safety reporting/DSURs); conducted formal meetings with CDER; prepared several gap analyses and regulatory development plans; ongoing review of public-facing information (e.g., websites, flyers, conference presentations) about investigational products; helped 1 organization find specialty investigational CDMO; and completed 1 CMC vendor qualification.

Late-stage development highlights: preparation of Phase 3 clinical regulatory strategies; developed several Phase 3 clinical trials; 1 late-stage gap analysis; supported 1 organization to secure external funding; supported 1 organization to divest product; helped 1 organization manage Phase 3/commercial CDMO; actively championed labeling negotiations for a new product pending approval; and ongoing ad promo strategy and document review.