Facet Life Sciences Quarterly Update Q2 – 2024

Ken VanLuvanee, President & CEO

Apologies for the delay—this past quarter, we’ve championed a large number of Sponsor-FDA meetings and have had even more informal interactions in our quest to accelerate the regulated development of ground-breaking and innovative products.  The FDA has also been hopping with several advisory committee meetings, a host of new guidances, and progress on important initiatives.  We are finally sending out our (slightly delayed) critical summary of things you need to know!

Accelerating the Development of a Novel Oncology Therapeutic Through a Simple Capsule Formulation Strategy

Facet helped a small company develop a relatively simple, quick, and cost effective approach for the manufacture of their clinical trial material for a Phase 1 trial in patients with advanced metastatic cancer.  The novel small molecule anticancer agent was known to have good chemical stability in buffered saline and simulated gastric and intestinal fluid, but poor aqueous solubility.  Formulation development led to an amorphous solid dispersion in capsules, which allowed the nonclinical program to advance at a much greater pace. This accelerated program allowed this small start-up pharmaceutical company to make the most of their limited time and financial resources.  The company will be able to start enrolling patients in their Phase 1 clinical study much earlier than expected; a key milestone for garnering additional and greater investment to continue both the clinical and CMC development phases of the drug campaign.

Facet Helps Small Company Secure Fast Track Designation

Facet helped a small, ex-US company apply for and receive Fast Track Designation for their new chemical entity.  A product may be eligible for Fast Track designation whenever it is being developed to treat a serious condition for which there is an unmet medical need.  Fast Track can also be requested if the product under development has superior effectiveness, avoids serious side effects, improves diagnosis for a serious condition, or has decreased toxicity compared to an approved product.  The Sponsor’s product in question qualified for Fast Track based on improving the diagnosis of a serious condition where early diagnosis is expected to improve outcomes for those impacted.  The request was granted in just over 40 calendar days (well within the 60 day FDA commitment).

Dana Blue, MS, a Strategic Program Champion at Facet said, “Receiving this designation has significant regulatory and business benefit for this small company because it allows for more frequent meetings with FDA to ensure the development program is sufficient and makes them eligible for Accelerated Approval and Priority Review or a Rolling Review of their application content.”

Supreme Court Overrules Chevron Deference – Supreme Court Overturns Chevron, What Now?

On June 28, the U.S. Supreme Court overturned the longstanding Chevron deference, a precedent that required courts to defer to federal agencies’ interpretations of ambiguous statutes. In the case of Loperbright Enterprises v. Raimondo, the Court ruled that judges must now make their own independent judgments on whether an agency’s interpretation of statutory language is reasonable. This shift could significantly impact FDA-regulated industries, potentially leading to more legal challenges against the agency’s rulemaking, particularly in areas like Laboratory Developed Tests (LDTs) and health-related software. Read the full article: Supreme Court Overrules Chevron Deference

FDA Final Guidance for Laboratory Developed Tests: FDA Issues Small Entity Compliance Guide

The FDA has issued final guidance for Laboratory Developed Tests (LDTs), marking a significant shift in how these tests are regulated. Originally intended for local use, LDTs are now classified as in vitro diagnostic products (IVDs) and will be regulated as medical devices under the Federal Food, Drug, and Cosmetic Act (FD&C Act). Starting May 6, 2025, the FDA will begin a 4-year phase-out of its general enforcement discretion approach, aiming to regulate all diagnostic products under targeted policies. Exceptions and specific enforcement discretion policies are detailed in the “Laboratory Developed Tests: Small Entity Compliance Guide” published on June 25, 2024. Read the full article: FDA Final Guidance for Laboratory Developed Tests

Update on Chinese and Indian Biotech In the Spotlight

The FDA recently announced that sponsors who used Synapse Labs Pvt. Ltd. in India for bioequivalence or bioavailability studies must repeat those studies due to concerns about the data’s validity. Additionally, FDA is changing the therapeutic equivalence ratings of FDA-approved generics supported by Synapse data to “BX,” indicating the data is insufficient for automatic substitutability at pharmacies. While FDA continues to accept data from ex-US organizations, it’s crucial for sponsors to closely monitor their partners to ensure compliance with global and FDA regulations. Read the full article: Update on Chinese and Indian Biotech

New RD Hub

On July 17, 2024, the FDA launched a Rare Disease Innovation Hub to support the development of therapies for rare diseases with small or poorly understood patient populations. The Hub will serve as a central point for the rare disease community, enhance FDA collaboration, and advance regulatory science. This initiative aims to bring innovative therapies to the over 10,000 rare disease patients in the U.S. Read the full article: New RD Hub

START Pilot Program Updates

The FDA’s START Pilot Program, designed to streamline the development of rare disease therapies, recently announced their list of pilot participants, with many being small organizations! While the program offers increased engagement with the FDA and faster regulatory milestones, a recent survey suggests that participation in FDA initiatives more broadly requires significant additional effort. At Facet, we’ve seen both the benefits and challenges of these programs and encourage small organizations to carefully consider the trade-offs before applying. If you’re interested in the START program, contact Facet today. For more information: START Pilot Program Updates

FDA Approves Ojemda

On April 23, 2024, the FDA granted accelerated approval to Ojemba (tovorafenib) for patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma with a BRAF fusion or rearrangement, or BRAF V600 mutation.  This is the first FDA approval of a systemic therapy for this pediatric cancer.  Another unique aspect of this approval is that the review used the FDA’s Assessment Aid, which is a voluntary submission from the applicant to facilitate the FDA’s review.

FDA Holds Two Groundbreaking Advisory Committee Meetings

Lykos MDMA

On June 4, 2024 the FDA held a much awaited advisory committee meeting to discuss the NDA submitted by Lykos Therapeutics for their MDMA product for the treatment of post-traumatic stress disorder (PTSD).  Read more on the website at: Special Topic: Lykos MDMA.

Lilly donanemab (Kisunla)

On June 10, the Peripheral and Central Nervous System Drugs Advisory Committee met to discuss the NDA submitted by Eli Lilly and Co., for donanemab solution for intravenous infusion for the treatment of early symptomatic Alzheimer’s disease.  Despite concerns about reduced effectiveness shown in clinical trials in patients with high tau PET levels at baseline and no data in patients with no or low tau levels at baseline, there was unanimous committee agreement on the efficacy of the product to treat Alzheimer’s disease.  Especially noteworthy, the committee also agreed that treatment with donanemab could be discontinued in patients who showed an  elimination of amyloid plaques on post-treatment imaging.  However, committee members agreed that although more research was needed to determine how long patients should be monitored, whether treatment should be reinitiated, and the safety associated with stopping and restarting donanemab treatment.  On July 7, FDA approved donanemab (Kinsunla), providing patients with a potentially disease-modifying treatment for this devastating disease and offering hope to millions of patients and their caregivers.

New FDA Guidance

Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies (Draft June 2024)

Submission of Diversity Action Plans is a federal requirement for certain clinical trials involving drugs, biological products, or devices.  In this guidance, the FDA outlines specific requirements for the content of Diversity Action Plans, including enrollment goals (disaggregated by race, ethnicity, sex, and age group), rationales for the goals, and measures to meet the goals, with the aim to increase enrollment of participants from historically underrepresented populations in clinical trials.  This guidance also includes information about the timelines and procedures for submitting Diversity Action Plans, as well as criteria for requesting waivers.  This guidance makes it easier for Sponsors to remain compliant with federal regulations, align with FDA expectations, and ultimately avoid delays in the review process due to a lack of population diversity in clinical trials.  While developing Diversity Action Plans may require additional resources and planning for Sponsors, it also presents an opportunity to improve the quality and generalizability of your clinical data, ultimately strengthening your marketing application. The guidance can be found here:  Emerging Drug Safety Technology Meeting (EDSTM) Program Overview.

Facet is helping Sponsors design and implement product development pathways in accordance with the new draft guidance.  Contact Facet if you have questions about how Facet can help you design and execute a lean, yet compliant development program!

Processes and Practices Applicable to Inspections of Sites and Facilities under FDA’s Bioresearch Monitoring (BIMO) Program, as Conducted in Accordance with Section 704(a)(5) of the Federal Food, Drug, and Cosmetic Act

In compliance with the Food and Drug Omnibus Reform Act of 2022, this draft guidance issued in June provides a description of the expectations and practices for site and facility inspections.  BIMO compliance programs are administered by the applicable FDA centers within the Office of Regulatory Affairs.  BIMO inspections may occur in any site or facility conducting research, both domestically and abroad, for any US application.  These inspections are conducted to confirm compliance with the BIMO compliance programs which include but are not limited to institutional review boards (IRB), and Good Laboratory Practice.

Sites and facilities may undergo several types of inspection.  Inspections are conducted to support the FDA’s review of an application but can occur periodically to monitor ongoing research activities.  Inspections can be conducted in response to a report or complaint from a sponsor or IRB to deduce if sites are noncompliant or using unsafe or unethical practices.  Inspections can be all encompassing or directed at specific parts of operations.

For Sponsors, it is important for you to know that FDA will typically let a site know when and where investigators will be arriving and will ask the site to provide the FDA inspector with everything needed for a successful inspection.  The site should be prepared to provide the inspector with any requested records including any electronic records.  The site is allowed to communicate with the inspectors prior to and during the inspection in order to understand the timeline, nature, and process.  The inspector will discuss findings with the staff in charge of the site while inspecting and will close out the inspection with a discussion of findings with the site representative and may issue a written FDA Form 483.  The FDA Form 483 is a notice of “objectional conditions and practices.”  If a FDA Form 483 is issued, the site has 15 business days to respond to the FDA to contest the observation or provide an action plan to correct and prevent the condition or practice.  FDA expects that the site will provide all appropriate documentation with their proposed plan.

The processes and practices applicable to BIMO inspections can be found in the FDA’s compliance programs, Investigations Operations Manual (IOM) and the Regulatory Procedures Manual (RPM).

Final Rule:  Direct-to-Consumer Prescription Drug Advertisements: Presentation of the Major Statement in a Clear, Conspicuous, and Neutral Manner in Advertisements in Television and Radio Format (Effective Date:  20 May 2024; Compliance Date:  20 November 2024)

In this final rule, the requirements for presenting risk information in direct‑to‑consumer television and radio advertisements for prescription drugs were amended.  The rule establishes 5 standards for presenting the major statement of side effects and contraindications in a clear, conspicuous, and neutral manner:

1. Language and terminology must be consumer‑friendly;
2. Audio must be at least as understandable as the rest of the advertisement in volume, articulation, and pacing;
3. For TV advertisements, major statement must be presented concurrently in audio and text (dual modality);
4. Text must be easily readable;
5. There should be no audio or visual elements during the presentation of the major statement that could interfere with comprehension.

The aim of this rule is to improve consumer understanding of drug risks and help ensure truthful and non‑misleading information in advertising.  It applies to both new and existing advertisements, and does not change the content of the major statement, only the manner in which it is presented.

Facet provides advertising and promotional support to many of our clients and can provide you with the necessary regulatory and scientific guidance to ensure you are getting the most out of your ad promo pieces while also remaining compliant with FDA regulations and guidances.

New FDA Meeting Type

Emerging Drug Safety Technology Meeting (EDSTM) Program

The EDSTM meeting aims to facilitate discussions about the use of AI and other emerging technologies in post-marketing pharmacovigilance.  Meetings can be requested by applicants with at least one approved application (NDA, ANDA, or BLA), or other relevant parties (e.g., academia, CROs/pharmacovigilance vendors, software developers) involved with research, development, and use of emerging technologies in the pharmacovigilance space.  This program may provide a competitive edge for small companies developing innovative technologies, as it offers an opportunity to discuss potential barriers to implementation with the CDER early in the development process.

In case you missed it, our team has been very busy this quarter! From attending key industry conferences to launching new initiatives, we’ve been actively engaging with the community and driving forward our mission.

Here’s a look at the key takeaways from the conferences and events our team attended this quarter. We’ve gathered valuable insights and best practices that we’re excited to share with you on our website, helping us all stay ahead in the industry.

• Facet Joins PET CMC Coalition
• Facet Attends the Food and Drug Law Institute (FDLI) Annual Conference
• Facet Attends the Market Access Society of America Symposium
• Facet Attends Psychedelic Therapeutics & Drug Development Conference
• Facet Attends SNMMI
• Facet Donates to SNMMI’s Mars Shot

Total ESG submissions to FDA Apr – June 2024:  Over 30!

Early-Stage Development Highlights

6 formal FDA meetings, 1 investigator-initiated IND, over 25 IND amendments (e.g., new protocols/amendments, CMC updates, nonclinical study reports, information amendments, IND annual reports, orphan designation annual reports, safety reporting/DSURs); prepared several gap analyses and regulatory development plans; ongoing review of public-facing information (e.g., websites, flyers, conference presentations) for investigational products; responded to numerous FDA information requests; supported initial CMC development of complex drug-device combination product; provided regulatory strategy and guidance for FDA meeting planning; provided IND strategy and planning; secured 1 breakthrough designation; secured 1 fast track designation; clinical trial simulations to improve trial design and probability of success.

Late-Stage Development Highlights

Prepared several gap analyses, Phase 2 and 3 clinical regulatory strategies; Phase 3 clinical trial oversight; used statistical modeling and simulations to design Phase 3 clinical trials; supported registration batch manufacturing; human factors study design recommendations; medical device development strategy for over 3 products; active regulatory submission planning for 3 NDAs/BLAs; designed and authored several protocols and clinical study reports; maintained CT.gov postings; actively engaged in investment/funding partnership support; and ongoing pre-approval ad promo strategy and content review.

Post-Approval and Commercial Highlights

Several NDA CMC supplements; labeling PAS; ongoing advertising and promotional review.

We are excited to announce the addition of 3 new team members.

Eva Raspor, Strategic Regulatory Writer

Facet welcomes Eva Raspor to our team as a Strategic Regulatory Writer.  Eva has a wealth of experience related to writing for multiple projects, indications, and applications.  Prior to joining Facet, Eva was already considered an expert writer for several regulatory documents.  Eva is originally from Slovenia and found her career by combining her knowledge of biology and neuroscience with her love of distilling complex information to its essence for ease of understanding.  Eva is looking forward to bringing her current expertise to Facet’s clients.  Eva has a Masters of Science in Neuroscience from Vrije Universiteit Amsterdam and a bachelors in Biology from University of Ljubljana.  Eva will provide regulatory writing support for IND, NDA, BLA, and medical device programs throughout all stages of development.

Amanda Austin, M.D., Strategic Regulatory Writer 

Facet welcomes Amanda Austin, M.D. to our team as a Strategic Regulatory Writer.  Amanda comes to us with over 5 years of experience writing both regulatory documents and journal articles for publication in top tier medical and scientific journals.  Prior to joining Facet, Amanda was a freelance writer contributing to various documents across multiple indications as well as a consultant Chief Medical Officer for various companies.  Prior to that, Amanda was an emergency room physician as well as a pediatric physician at a hospital in Indiana.  Amanda’s expertise lies with regulatory writing and publication planning and execution.  Amanda is looking forward to bringing her current expertise to our clients.  Amanda has a Doctor of Medicine degree from Southern Illinois University School of Medicine and a bachelors in Biology from Westmont College.  Amanda will provide regulatory and publications support for IND, NDA, BLA, and medical device programs throughout all stages of development.

Rob Vollkommer, Project Manager

Facet welcomes Rob Vollkommer to our team as Project Manager.  Rob has several decades of experience managing various types of initiatives, from both a business development and project delivery perspective.  His foray into Life Sciences began in the early 1990’s in the area of clinical trials management where he managed a global team through business process redesign, software selection, and implementation.  As a dedicated life sciences professional, he worked in many other areas including Sales Force operations, real world data/research, pharmacovigilance before having the opportunity to experience the exciting world of regulatory submissions from 2011 – 2022 while working at CSC/DXC and Red Nucleus. Prior to joining Facet, Rob worked as a senior Account Management and Business Development Executive in the life sciences industry for companies like Iron Mountain, IQVIA, Red Nucleus, CSC/DXC, Accenture and others. Rob will provide project management support, including preparing and maintaining IND, NDA, BLA, and medical device submission project plans, managing team resources and deliverables, and project-related business operations.

At Facet, our mission is to make life sciences dreams a reality.  We are looking for a regulatory affairs team leader and lead CMC regulatory strategists who want to use their knowledge and experience to help small organizations get their innovative products from concept into development, through FDA, and on to US commercial launch.

For over 10 years, Facet has leveraged our strong scientific, development, and regulatory expertise to help small organizations reach successful outcomes, from product concept to FDA approval.  We love to tell a good story and great science makes for a great story.

Come help us create great success stories – both for our customers and for you!

Join our Team