Warren Alpert Prize Honors Five Pioneers in Cystic Fibrosis

Five scientists whose work has been instrumental in developing disease-modifying treatments for cystic fibrosis (CF) are recipients of the 2018 Warren Alpert Foundation Prize.

Until recently, therapies for CF targeted only the symptoms of the disease. The U.S. Food and Drug Administration (FDA) approved the first disease-modifying therapy, Kalydeco (ivacaftor, marketed by Vertex Pharmaceuticals), in 2012. Since then, two more disease-modifying therapies have been approved (Orkambi and Symdeko) and several more are in clinical trials.

This year’s prize honored scientists who contributed to the discovery of the CTFR gene (the gene that is defective in CF) and the approval of disease-modifying therapies.

The recipients are:

• Francis Collins, MD, PhD, director of the National Institutes of Health (NIH);
• Paul Negulescu, PhD, senior vice president for research at Vertex Pharmaceuticals;
• Bonnie Ramsey, MD, vice chair and endowed professor of pediatrics at University of Washington School of Medicine, and director of the Center for Clinical and Translational Research at Seattle Children’s Research Institute;
• Lap-Chee Tsui, PhD, founding president of The Academy of Sciences of Hong Kong, and university professor emeritus at University of Toronto, and;
• Michael Welsh, MD, professor of internal medicine — pulmonary, critical care and occupational medicine at University of Iowa.

Tsui and Collins’ work led to the discovery of the CTFR gene, its location, and its impact on the disease. Welsh’s work determined the function of the CTFR protein, and how the mutated gene hindered its ability to transport chloride in and out of cells. Ramsey built the clinical trial networks that brought disease-modifying therapies to FDA approval. And Negulescu led a Vertex Pharmaceuticals’ team that identified compounds and developed the first therapies that directly modify the function of the CFTR protein.

“The work of the five scientists we are honoring is a triumph of modern medicine,” Joseph Martin said in a press release. Martin is director and chairman of the board of the Warren Alpert Foundation and former dean of Harvard Medical School. “We are humbled by the passion, dedication and acumen of a truly remarkable group of individuals whose achievements have touched the lives of patients and families across the world.”

Cystic Fibrosis News Today asked Negulescu for his thoughts on this honor toward the close of an unrelated interview.

By winning the award, Negulescu said he hopes to help tell “the story of how much goes into this process of taking the basic science discoveries all the way to a patient.” The award, he added, “is an opportunity to help share a really inspiring story that I hope reminds people of the value of the health system and the cost of innovation.”

Negulescu led a long-term research project at Vertex that ultimately led to the approval of three therapies — Kalydeco (in 2012), Orkambi (in 2015) and Symdeko (earlier this year) — that address the underlying defect responsible for CF. All three therapies have been shown to restore CFTR function and improve lung function in CF patients with specific CFTR mutations.

Negulescu and his team now are developing triple combination therapies to address several other CFTR mutations. The underlying idea is to offer one or more viable therapeutic options to up to 90 percent of all CF patients.

The Warren Alpert Prize

The Warren Alpert Foundation has awarded the prize annually, in conjunction with Harvard Medical School, since 1987, recognizing scientists whose work has affected a variety of diseases, ranging from diabetic retinopathy to muscular dystrophy, heart attacks, and cancer. To date, the foundation has awarded more than $4 million to 64 researchers.

“Over the years, the Warren Alpert Foundation has honored some of the most elegant and transformative scientific achievements of our time,” said George Q. Daley, MD, PhD, dean of Harvard Medical School.

Referring to this year’s awardees, Daley said: “The five scientists’ collective work powerfully illustrates the promise of basic discoveries made in the lab to profoundly alter the lives of patients through collaboration among fundamental researchers, biochemists and frontline clinicians.”

This year’s winners will be recognized at a scientific symposium at the Harvard school on Oct. 4. Four of the five honorees will share a $500,000 prize (Collins declined the financial reward.)

“I’m deeply honored and humbled to have been recognized with the award. It’s a recognition of the work that so many people have done over so many years and I was just a small part of it,” Negulescu said.