The National Institutes of Health (NIH) is shifting its focus towards clinical trials for long COVID treatments through its RECOVER initiative. This change comes after facing criticism for primarily allocating its nearly $1.7 billion funding to research aimed at understanding the condition rather than testing potential therapies. The new phase, named RECOVER-TLC (Treating Long COVID), will be led by the National Institute of Allergy and Infectious Diseases (NIAID) and aims to accelerate the development of medical options for the millions suffering from long COVID.
RECOVER-TLC: A New Phase
RECOVER-TLC represents a significant shift in the NIH's approach to long COVID. Unlike the initial phase of RECOVER, the TLC phase will concentrate on clinical trials. NIAID Director Jeanne Marrazzo will oversee a dedicated team focused on long COVID clinical trials, ensuring direct reporting and efficient management of the initiative.
By the end of the month, RECOVER plans to launch the RECOVER-TLC Intervention Information Request Form, a portal designed for drugmakers and researchers to submit potential treatments for consideration. Marrazzo emphasized the importance of rapid responses to these submissions, aiming to expedite the evaluation process.
Addressing Criticisms and Streamlining Protocols
The shift towards clinical trials addresses criticisms that the initial RECOVER initiative was slow to fund treatment-focused studies. Launched in 2021, RECOVER did not begin funding clinical trials until mid-2023, and some of these studies tested non-pharmaceutical interventions like therapeutic video games and exercise therapy. Critics argued that focusing on pharmaceutical interventions is crucial, as it requires physician access and clinical trials to test medications effectively.
Some biotech executives, including Tonix Pharmaceuticals CEO Seth Lederman and Aim ImmunoTech CSO Christopher McAleer, have emphasized the need for streamlined, widely accepted protocols for long COVID clinical trials. Lederman noted that clear protocols could attract private investors who are currently hesitant due to the lack of a clear path to approval. McAleer suggested that RECOVER-TLC should focus on generating data that can be used for FDA approval, addressing the current obstacles to industry investment in long COVID drug development.
Defining Trial Endpoints: A Major Challenge
A significant challenge for RECOVER-TLC will be defining appropriate trial endpoints. Long COVID presents differently in each patient, affecting various systems such as the gut, brain, cardiovascular system, and endocrine functions. Symptoms often overlap with other conditions like myalgic encephalomyelitis, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and fibromyalgia.
Paul Lee, deputy director of the FDA’s Office of Neuroscience, described long COVID as a disease with many different manifestations. Researchers are considering various metrics, including biomarkers like microRNAs or microclots, and non-biological measures such as clinically validated questionnaires for fatigue and cognitive function.
Patient Access and Trial Design
Access to medical centers for tests like blood draws and bone marrow biopsies poses a significant challenge for many long COVID patients. Decentralized trials that allow remote participation are essential to include those with severe cases who cannot leave their homes. Additionally, the use of placebo controls raises concerns, as patients may prefer accessing existing treatments for overlapping conditions like POTS and MCAS outside of a trial setting.
Josh Fessel, director of the Office of Translational Medicine at the National Center for Advancing Translational Sciences, emphasized that the success of these studies hinges on robust study design. NIAID is likely to approve multiple types of trials to address these challenges.
The Path Forward
Lisa McCorkell, cofounder of the Patient-Led Research Collaborative, supports NIAID's approach and suggests appointing a leader to spearhead the greenlighting process. She highlighted the critical importance of RECOVER-TLC for long COVID patients, emphasizing that their lives depend on turning this meeting into action.
