Heading into 2024, as with any annual flip of the calendar, we anticipate there will be things that will fade away, things that will persist, and things that will develop — in the clinical research industry as in life. And so, when Clinical Leader asked experts across the continuum about their thoughts for the new year, we got a little bit of everything. Many people opined on the pervasiveness of AI, whether that’s in patient recruitment or regulatory oversight, a few acknowledged the persistence of the decentralized trial in all its many forms, and others saw gains and changes coming in their own therapeutic areas.
In part four, experts discuss several therapeutic areas and their advancements they believe deserve and will garner interest in 2024.
Oncology Dose Optimization And Accelerated Approvals
Marjorie Zettler, senior director, clinical science, Accutar Biotech
As we move into 2024, we can expect to see dose optimization trials for oncology drugs become increasingly common. In recent years, there’s been a growing recognition of the critical importance of dose optimization in the premarketing setting. Although the therapeutic landscape for cancer has undergone dramatic changes over the past two decades, dose-finding methodology developed for cytotoxic chemotherapy has remained standard practice, and as sponsors have pushed to deliver new therapies to patients with cancer as quickly as possible, dose optimization has been an afterthought, deferred to the post-marketing period or skipped over altogether. The FDA’s launch of Project Optimus in 2021, and issuance of draft guidance for industry in 2023, spelled out the agency’s rationale for breaking with historical dose-finding practices in oncology and firmly established their view of dose optimization as an integral part of the preapproval drug development process. While the guidance document is still draft and there are still some outstanding questions about the specifics for these trials, the expectation that industry sponsors of oncology drugs should be building dose optimization into their clinical programs is clear.
Another trend we may see in oncology drug development in 2024 relates to clinical trials supporting accelerated approvals. Over the past few years, FDA has undertaken multiple initiatives to address the issue of “dangling” accelerated approvals, which have included the launch of Project Confirm in 2021, Oncology Drug Advisory Committee meetings to review accelerated approvals for indications with failed (or significantly delayed) confirmatory trials, and draft guidance for industry issued in 2023 on clinical trial considerations to support accelerated approval of oncology therapeutics. The guidance document states that confirmatory trials to verify clinical benefit should be underway at the time of accelerated approval, a position reiterated by the director of FDA’s Oncology Center of Excellence, Richard Pazdur, MD, at the 2023 Friends of Cancer Research Annual Meeting. Notably, Dr. Pazdur expressed the expectation that confirmatory trials should be substantially enrolled at the time of accelerated approval and that sponsors who wanted to test this could anticipate “tough love” from the FDA.
Gene Therapies And, Again, Accelerated Approvals
Carolyn Sasse, development division head of cell and gene therapy, Astellas Gene Therapies
We are entering an exciting era in the gene therapy landscape. This past year, we saw Sarepta’s gene therapy Elevidys granted accelerated approval by the FDA, Hemgenix approved by EMA, and the first-of-its-kind gene-editing treatment exagamglogene autotemecl approved by the MHRA and under review by FDA and EMA. The number of approvals is anticipated to grow in the coming years, bringing the potential to achieve positive outcomes for even more patients around the globe. With even more therapies on the verge of becoming first-line options for several rare genetic diseases, the clinical development strategy, regulatory approval, and reimbursement process are critical to creating true value for patients and their caregivers.
CBER continues to evolve its approach. It has been leveraging best practices from other divisions to support the acceleration of approvals based on surrogate endpoints as well as the initiation of Support for clinical Trials Advancing Rare disease Therapeutics (START), a pilot program with the intent to increase communication between the FDA and industry. The opportunity to seek the agency’s advice throughout the development process should lead to more efficient decision-making and earlier course correction, improving the speed at which these gene therapies are approved. Success will be measured by the patients’ ability to access these treatments. To achieve this collectively with patients, trials must be designed that will support approval and reimbursement. Payors must see the value of a one-time gene therapy treatment that often comes with a steep price tag. Payors will need to approve treatment based on endpoints that are expected to predict the clinical benefit and durable effect. Industry will need to continue to improve its technology and create innovative approaches that decrease the cost of goods. Each stakeholder must listen to the voice of the patient and caregivers to be successful in executing earlier access. Industry, health authorities, and payors must adapt their strategies to account for what patients and their caregivers value and create a truly patient-centric approach.
I envision that given these new opportunities created to accelerate approvals and the ability to obtain reimbursement for gene therapies, we will see more companies prioritizing the incorporation of the patient and caregiver voice in drug development — finding ways to partner with the patient community to identify meaningful quality-of-life endpoints — and working with regulatory agencies and payors to gain support for these quality-of-life endpoints.
Autoimmune Disease Therapy Investments
Aileen Pangan, vice president and therapeutic area head, immunology clinical research at Merck Research Laboratories
New therapies for autoimmune diseases that can provide sustained remission or symptom relief and ultimately help people live more fully, are greatly needed. With an advanced understanding of human biology, there has been an emergence of innovative medicines and new modalities that aim to change the way we approach treatment for autoimmune diseases.
At Merck, we’ve made significant investments over the past few years and hope to usher in a new era in immunology. We are working on ways we can enhance the body’s own regulatory system to control inflammation and pursuing biomarkers that could play a key role in identifying people who are more likely to respond to therapies. By mining one of the world’s most comprehensive repositories of IBD scientific and clinical data, we’re yielding important disease insights that we can leverage as we aspire to bring precision medicine to immunology.
Ramita Tandon, chief clinical trials officer, Walgreens
Efforts to improve women’s health research will be front and center in 2024. Despite making up more than half of the population, issues predominately impacting women continue to be under-researched, which has had significant consequences on women nationally. Both the public and private sectors will be involved in this movement, as President Biden recently announced a new White House initiative to close gaps in women-focused health research emphasizing collective action from across industries. Healthcare organizations with roots in local communities and female consumer bases, like Walgreens, will be instrumental to furthering the initiative’s goals through targeted outreach, education, and tailored clinical trial recruitment.