The U.S. Food and Drug Administration (FDA) recently gave approval of the drug Nucala (mepolizumab) to treat hypereosinophilic syndrome (HES). This milestone has led many within the eosinophilic community to look back on the decades-long journey to this achievement, including Bill H., a former patient who first received this drug in the early 2000s at Cincinnati Children’s.
For years, Bill H. wondered what was wrong with him. Random infections and trips to the emergency room had become more and more common after he turned 50 years old, but despite visits to a variety of specialists, the cause for his ailments remained a mystery.
“In the late 1990s, I had recently turned 50 and began to develop random infections—sinus, ear and bladder, as well as bronchitis—that left my local doctors puzzled for the cause,” said Bill.
His search for a diagnosis continued for several years.
“I would be treated with prednisone and a variety of antibiotics, but no one ever got to the root cause of the illnesses, although lab work consistently indicated elevated eosinophil count," said Bill. "Due to difficulty breathing, I was a regular visitor to the local emergency room, where I was known as ‘the eosinophil guy’.”
In his search for answers, Bill tried alternative homeopathic cures, acupuncture, and changed his diet to avoid gluten. Nothing worked.
“Skin rashes were painful and embarrassing. This continued until I developed an immunity to several antibiotics and a dependency on prednisone. When my doctor diagnosed me with ‘bad luck’, I started seeing specialists, pulmonologists, neurologists and allergists,” said Bill, who now lives in New Hampshire.
After a recommendation from a local allergist, Bill met with Dr. Joshua Boyce at the Department of Allergy and Immunology at Brigham and Women’s Hospital in Boston, where he was finally diagnosed with hypereosinophilic syndrome (HES).
HES is a life-threatening group of blood disorders that involve having high levels of eosinophils, a type of white blood cell that plays an important role in the immune system. Over time, these overly high levels of eosinophils, called eosinophilia, enter tissues and organs and cause damage. Until now, high doses of corticosteroids were used to lower eosinophil levels to prevent damage to organs. However, disease flares still happen, and these disease flares cause dangerous damage to the body.
Bill tried several medications, but none were effective. Boyce then recommended that Bill travel to Cincinnati Children’s and meet with Marc Rothenberg, MD, PhD, director of the Cincinnati Center for Eosinophilic Disorders.
At the time, Rothenberg was beginning to study the effects of the anti–interleukin 5 (IL-5) mepolizumab for the treatment of eosinophilic disorders. Bill became a patient and saw positive results soon after.
“I became a participant in the initial phase I/II study of mepolizumab in 2002-2003. I immediately found a dramatic and rapid effect on my health and well-being. My eosinophil count returned to normal, my breathing improved, and I was able to reduce dependency on steroids,” he said.
Rothenberg recalls his participation in the initial clinical study of the drug in 2002. The study was supported by a competitive grant that Rothenberg had received from the FDA’s Office of Orphan Product Development. At the time, he was hoping to find new therapeutic options for individuals like Bill with HES.
“Early research in our division pioneered the first usage of mepolizumab in patients with HES through an open-label, FDA-sponsored study in which patients with HES were intravenously infused with mepolizumab at Cincinnati Children's,” said Rothenberg. “A striking drop in their blood eosinophil levels was found. These findings prompted the prolonged development pathway of mepolizumab for HES.”
The drug mepolizumab targets interleukin-5, a chemical produced by the body that acts as a growth factor for eosinophils and that Rothenberg had been studying in the research lab as part of his long-standing work to decipher mechanisms of eosinophilia and treat eosinophilic diseases.
“Despite delays, it is truly rewarding to see this treatment now approved for HES,” says Rothenberg.
For Bill, his journey continued past that initial phase I/II trial, and he now thanks Rothenberg for the work that he has done towards drug approval and Boyce for his dedicated care.
“Following the study, I continued to receive mepolizumab through additional studies. I am in my 17th year on mepolizumab and receive infusions of 500 mg at 8-week intervals at Brigham and Women’s Hospital in Boston,” he said.
Boyce and his staff in Boston continue to work closely with Bill. The team helps with evaluating medications, reviewing test results and lab work, communicating with his specialists and primary doctor in New Hampshire and submitting the necessary applications and reports to GSK so that Bill can receive his medication through their compassionate use program.
“Today, at age 74, I am in excellent health with consistently normal lab work and am enjoying retirement with a renewed sense of health, physical fitness and well-being. I really credit the quality of my life to this medication,” said Bill.
(Published October 2020)