Global Lupus Experts Recommend Changes to Clinical Trial Outcome Measures to Expedite Development of Therapeutics

Lupus is a complicated and debilitating autoimmune disease, affecting millions of people across the globe. Yet, lupus drug development lags behind that of other rheumatic diseases, likely due to the complexity of the disease. To address the urgent need to develop therapeutic solutions, the Addressing Lupus Pillars for Health Advancement (ALPHA) Project Global Advisory Committee (GAC) is recommending significant changes to lupus clinical trial outcome measures. In a new report, “The ALPHA Project: A Stakeholder Meeting on Lupus Clinical Trial Outcome Measures and the Patient Perspective,” published in Lupus Science & Medicine, the GAC and other key experts discuss how lupus disease complexity dictates necessary changes to clinical trial outcome measures, including incorporating patient voice and preference, to facilitate drug development progress.

“The heterogeneity of lupus and its varied organ system manifestations make it challenging to adequately capture disease activity in all. Validation of newly developed clinical trial outcome measure tools is difficult for this very reason,” says Karen H. Costenbader, MD, MPH, report author and Lupus Foundation of America Medical-Scientific Advisory Council Chair and Director of the Lupus Program at Brigham and Women’s Hospital. “Consensus across the lupus community to simplify and standardize clinical trial outcome measures would provide a more promising avenue for evaluating the success of interventions for various lupus subtypes across age groups. This stakeholder meeting led by the ALPHA Project’s GAC was a necessary first step in understanding new approaches to capturing disease activity in clinical trials and strategizing on next steps for effectively approaching regulatory bodies, including the U.S. Food and Drug Administration (FDA), to make the case for approval of more powerful tools that will help the future of lupus drug development.”

The ALPHA GAC members who serve on the drug development team, which include lupus physicians, biotechnology experts, patient advocacy group representatives from the Lupus Foundation of America (LFA), and advocacy/government consultants, worked together to review and discuss completed and existing outcome measure development efforts.

Discussions revealed challenges of working with the FDA to get tools approved for use in lupus therapeutics development clinical trials:

• Largely due to the disease’s complexity, therapies for lupus may target different symptoms and, therefore, fall under the purview of different FDA review divisions, requiring greater navigation and coordination.
• The variation in outcome measure expectations across the agency, in turn, further complicates efforts to develop simple, comprehensive tools for lupus.

The experts concluded that a consensus on what feedback is needed from the FDA could be helpful to inform future efforts to develop or refine lupus outcome measures. To improve lupus therapeutics development, experts agree on the following:

• Approaches to outcome measure development should be patient-centric and take into consideration factors most important to patients regarding their health.
• Sharing of datasets from trials that did not reach clinical endpoints to ascertain a new outcome measure’s ability to detect improvements and/or worsening of disease.
• Multiple outcome measure efforts should continue running independently to help keep momentum as researchers and sponsors address varying feedback from the FDA.

Overwhelmingly, experts believe elevating the patient voice – both adult and pediatric – and adhering to their preferences is paramount in development of any new clinical outcome measure. Only one lupus outcome measure tool includes patient-reported and clinician-reported outcomes, the Lupus Foundation of America Rapid Evaluation of Activity in Lupus measure developed by LFA in concert with Dr. Joan Merrill and Dr. Anca Askanase. Other tools, such as the Treatment Response Measure for SLE tool effort led by Dr. Eric Morand at Monash University, are underway.

In 2019, the LFA launched the ALPHA Project, a comprehensive, multi-phase, global consensus initiative aimed at identifying and addressing the most pressing barriers to improving lupus outcomes. To date, the GAC has identified key barriers to improving lupus outcomes, as well as identified and prioritized actionable solutions for three overarching issues: clinical care, drug development and access to care.

For more information on the ALPHA Project and to follow ongoing developments, including forthcoming reports, visit lupus.org/ALPHA.