Triple-Drug Therapy for Cystic Fibrosis Wins 2025 Lasker Award

A story of how decades of science and persistence reshaped a once-fatal disease

For most of the 20th century, a diagnosis of cystic fibrosis (CF) meant a shortened life defined by relentless lung infections, repeated hospitalizations, and the need for daily, exhausting treatments just to breathe. Median survival hovered below 30 years. Families and physicians could only manage symptoms, never the root cause.

That trajectory changed in 1989, when researchers discovered mutations in the CFTR gene as the underlying driver of the disease. The finding set off decades of work to understand how a single defective protein could clog lungs with mucus, disrupt digestion, and eventually destroy organs. Thirty-five years later, the Lasker~DeBakey Clinical Medical Research Award recognizes three scientists whose contributions turned molecular insight into life-saving therapy: Michael Welsh (University of Iowa), Paul Negulescu (Vertex Pharmaceuticals), and Jesús “Tito” González (Integro Theranostics, formerly at Vertex Pharmaceuticals).

From biology to breakthrough

• Michael Welsh charted the fundamental biology of CFTR, showing how mutations disrupted the chloride channel and altered airway physiology. His lab also built cellular and animal models that allowed others to probe the disease mechanism.
• Jesús “Tito” González transformed that biology into a practical drug-discovery toolkit. At Aurora Biosciences/Vertex, he designed high-throughput cell-based assays capable of screening thousands of compounds, a pivotal advance that enabled the identification of CFTR modulators.
• Paul Negulescu led the translational effort, guiding candidate molecules from lab assays into clinical proof-of-concept. He played a central role in moving ivacaftor — the first CFTR modulator — and the subsequent triple-drug regimen into trials that transformed patient outcomes.

Each step depended on the last. By the late 2010s, researchers realized that many patients needed not just one drug, but a combination: some compounds to stabilize misfolded CFTR, others to enhance its channel activity.

Why three drugs?

Ivacaftor, a “potentiator,” improved gating of the channel but worked for only a minority of patients. Tezacaftor and elexacaftor, “correctors,” helped misfolded CFTR reach the cell surface. Together, the triple regimen (elexacaftor/tezacaftor/ivacaftor, or ETI) addressed the common F508del mutation carried by about 90% of patients.

Large clinical trials confirmed the impact. In one pivotal NEJM study, patients with at least one F508del allele saw their lung function (FEV₁) rise by nearly 14 percentage points, pulmonary exacerbations drop by more than half, and quality-of-life scores climb within weeks. For many, it was the first therapy that treated the cause of their disease rather than just its complications.

A medical turning point

Approved by the FDA in 2019 and rapidly adopted worldwide, ETI has redefined the natural history of CF. Children starting treatment early may avoid lung damage altogether, while adults have reported reclaiming daily activities once thought impossible. What was once a fatal childhood disease is now a manageable condition for most patients.

Still, challenges remain. Not all CF mutations respond to ETI, access is uneven across health systems, and the therapy must be taken for life. Gene-editing and mRNA-based strategies are in development, aiming for a one-time cure.

Why the Lasker matters

The Lasker Awards, often called “America’s Nobels,” honor discoveries that fundamentally change medical practice. Many recipients have later gone on to win Nobel Prizes. This year’s award signals not only the triumph of CFTR modulation but also the collaborative arc of modern translational medicine — from gene discovery to molecular biology to industry-led drug development.

For patients and families living with CF, it is more than recognition. It marks the moment their disease was transformed from an early death sentence into a chronic condition — and a reminder that decades of persistence in the lab can rewrite the future of human health.

Sources

• Lasker Foundation. Combined triple-drug therapy for cystic fibrosis. 2025.
• Veit G, Avramescu RG, Chiang AN, et al. Mechanisms of CFTR modulation by triple therapy. J Clin Invest. 2025.
• Middleton PG, Mall MA, Dřevínek P, et al. Elexacaftor–Tezacaftor–Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N Engl J Med. 2019;381:1809–1819.
• Vertex Pharmaceuticals. Vertex scientists awarded 2025 Lasker~DeBakey Clinical Medical Research Award.
• Andersen DH. Cystic fibrosis of the pancreas and its relation to celiac disease. Am J Dis Child. 1938;56(2):344–399.
• Riordan JR, et al. Identification of the cystic fibrosis gene. Science. 1989;245:1066–1073.
• Ramsey BW, et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011;365:1663–1672.