Nonclinical models are limited, and clinical trials are challenging because, among many factors, is that pain is subjective, making it hard to define objective endpoints or to compare one drug to another.
FDA is under tremendous pressure from Congress, state officials and the public health community to do more to address the national epidemic of opioid abuse that is causing thousands of deaths and medical emergencies. But while patients and providers demand effective treatments for chronic and acute pain, the public wants safeguards to prevent overdosing and misuse of these products. Drug labels, boxed warnings, prescriber education and postapproval monitoring have not deterred abusers. Now FDA Commissioner Robert Califf and agency leaders are implementing a new Action Plan to address the problem more forcefully, and hopefully to quell critics on Capitol Hill and in the medical community.
One important element of the plan is to encourage development of new, more effective pain medications with abuse deterrent (AD) properties, an issue addressed at the March 1 meeting of the FDA Science Board. FDA is reassessing how it weighs risks and benefits in approving opoid medications, and expanded use of its advisory committees is part of this process.
A main FDA strategy in recent years has been to encourage development of abuse-deterrent formulations (ADFs) of opioids. Five products with AD claims in labeling have been approved by the agency, supported by guidance finalized in 2015 on what studies and data is needed to support AD product development and approval. The Office of New Drugs (OND) in the Center for Drug Evaluation and Research (CDER) is evaluating some 30 active INDs for these products and other new technologies.
Despite these efforts, many development programs for new pain medicines fail, said Sharon Hertz, director of the Division of Anesthesia, Analgesia and Addiction Products in OND. There are many sources of variability in clinical analgesic trials, which makes it very difficult to measure treatment effect, Hertz explained at the Science Board meeting. Nonclinical models are limited, and clinical trials are “very challenging,” she noted, because pain is very subjective, making it hard to define objective endpoints or to compare one drug to another. It also is difficult for a study to enroll a population of pain patients that are able to respond to the test drug. Inadequate bioavailability of the test drug creates problems, as does study blinding when the test drug has specific adverse events. And there are limits on how long patients can remain in pain before administering a rescue medication, and that action can reduce study effect size and confound adverse events.
Consequently, just two out of 100 trials get past Phase II, Hertz pointed out. Sponsors have to ask, “how many failed studies can you survive before you have to give up on the drug program.”
FDA seeks to address such R&D issues through collaboration with academics, health professionals, advocacy groups and industry. The aim is to gain consensus on standards for measuring pain intensity and on different outcomes in clinical studies and to optimize clinical trial methods to increase study efficiency. FDA officials also will be seeking more advice on these and related issues from advisory committees, as part of its plan to have these expert panels consider the approval of new opioid formulations, particularly treatments for children. The agency’s action plan also calls for further guidance and recommendations for developing and approval of generic ADFs, which aims to increase prescriber uptake of these safer products. A main goal is to provide a broader range of treatment options for patients and prescribers, particularly therapies that are less attractive to abusers and addicts.
Behind the Buzz: Why Clinical Research Leaders Flock to SCOPE Summit
February 7th 2025In this episode, we meet with Micah Lieberman, Executive Conference Director for SCOPE Summit (Summit for Clinical Ops Executives) at Cambridge Innovation Institute. We will dive deep into the critical role of collaboration within the clinical research ecosystem. How do we bring together diverse stakeholders—sponsors, CROs, clinical trial tech innovators, suppliers, patients, sites, advocacy organizations, investors, and non-profits—to share best practices in trial design, program planning, innovation, and clinical operations? We’ll explore why it’s vital for thought leaders to step beyond their own organizations and learn from others, exchanging ideas that drive advancements in clinical research. Additionally, we’ll discuss the pivotal role of scientific conferences like SCOPE Summit in fostering these essential connections and collaborations, helping shape the future of clinical trials. Join us as we uncover how collective wisdom and cross-industry partnerships are transforming the landscape of clinical research.
Reaching Diverse Patient Populations With Personalized Treatment Methods
January 20th 2025Daejin Abidoye, head of solid tumors, oncology development, AbbVie, discusses a number of topics around diversity in clinical research including industry’s greatest challenges in reaching diverse patient populations, personalized treatment methods, recruitment strategies, and more.
Phase III Trial Data Show Subcutaneous Pembrolizumab as Noninferior to IV Keytruda
March 31st 2025Subcutaneous administration of pembrolizumab with chemotherapy demonstrated a nearly 50% reduction in patient chair and treatment room time while maintaining efficacy and safety endpoints compared to intravenous Keytruda.
Phase II ALPACA Trial Shows Lepodisiran Produces Significant, Sustained Lipoprotein(a) Reductions
March 31st 2025Eli Lilly’s lepodisiran, an investigational siRNA therapy, achieved significant and durable reductions in lipoprotein(a) levels, a major genetic risk factor for cardiovascular disease.