An OMRF physician-scientist is spearheading a call for transformative changes in clinical trials for new lupus drugs. In a new paper Joan Merrill, M.D. led a large team of lupus specialists and treatment developers to detail approaches that could lead to new and effective drugs reaching hospitals and clinics.
“In a nutshell, the goal of the paper is to create a dramatic shift in how lupus clinical trials are conducted so effective treatments can stand a chance to succeed,” said Merrill, Director of Clinical Projects in the Arthritis and Clinical Immunology Program at OMRF, who also serves as the Lupus Foundation of America’s Chief Advisor of Clinical Development.
The paper addresses long-standing barriers that have limited the development of new treatments for lupus. Only one new drug, belimumab, has been approved since the 1950s.
“I have been involved in more than 30 failed clinical trials since the 1990s, and they did not all need to fail. Because of the way things have been set up, a lot of these drugs will never be made available even though they might have been effective,” said Merrill.
Lupus is a chronic autoimmune disease that can cause unpredictable flares of inflammation affecting almost any organ in the body. While the disease can be relatively mild in some people, it can become serious and even fatal for others, causing serious damage to the brain, heart, kidneys or lungs.
According to the LFA, more than 1.5 million Americans have one or more form of lupus, which primarily strikes women. The standard of care relies on trial and error, primarily using treatments borrowed from other illnesses that have not been properly studied in lupus.
In the paper, Merrill and her colleagues propose making it possible to test more treatments by decreasing the size of trials. This can be accomplished through designs that increase the differences that can be detected when effective treatments are given, while reducing false impact from ineffective agents. The specific recommendations about how to do this are based on the analysis of many past, disappointing studies in lupus, and include the evaluation of more clear-cut disease manifestations, more stringent endpoints and use of current scientific advances to help select patients most likely to benefit from a specific therapy.
“If you take these ideas and apply them to clinical trials, we will be able to interpret the data better,” said Merrill. “This could lead to more approvals of effective drugs and will prevent ineffective drugs from succeeding. That would be huge, because our patients need safer and more effective treatments.”
The group also urged a community-wide effort to make trials available to patients with more types of lupus and to more minority patients, who, when left out of trials are also left out of access to new treatments that could work for them.
Merrill authored the paper, which appeared in the journal Lupus Science & Medicine, with substantial input from Susan Manzi, M.D., M.P.H., Chair of the Medicine Institute at Allegheny Health Network and Medical Director of the Lupus Foundation of America, and Victoria P. Werth, M.D., Professor of Dermatology and Medicine at the University of Pennsylvania School of Medicine, as well as a large group of leading lupus clinicians and trialists, and advice from biopharmaceutical experts. The Lupus Foundation of America will be presenting the findings of this paper to the FDA in the coming months.
At OMRF, Dr. Merrill works closely with Dr. Judith James, Head of the Arthritis & Clinical Immunology Program, in designing trials for lupus that are linked to complex immunologic profiling of the patients.
“We are working on small pilot projects to bring lupus treatment kicking and screaming into the 21st century,” she said.