3 Vertex researchers win $3M prize for CFTR modulator discoveries

Their research led to 4 approved CFTR modulators that target cause of CF

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Researchers from Vertex Pharmaceuticals have been awarded the 2024 Breakthrough Prize in Life Sciences for their work developing CFTR modulator therapies for people with cystic fibrosis (CF).

Breakthrough Awards, known as the “Oscars of Science,” are granted to scientists who have made important discoveries in life sciences, fundamental physics, and mathematics. Eight of the 11 award recipients this year were in the life sciences field, which also included the three Vertex researchers Paul Negulescu, PhD, Fredrick Van Goor, PhD, and Sabine Hadida, PhD.

Research over the last two decades, spearheaded by these scientists, has led to the development of four approved CFTR modulators, the only class of available medications that directly target the underlying cause of CF. The three researchers will share a $3-million prize.

“This prize recognizes the dedication and creativity of thousands of people at Vertex spanning research, development, regulatory, manufacturing and patient access, as well as our partners in the CF community, who have worked tirelessly to bring these medicines to people with CF around the world,” David Altshuler, MD, PhD, executive vice president of global research and chief scientific officer at Vertex, said in a company press release.

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In 1989, researchers discover CFTR gene mutations responsible for causing CF

In 1989, researchers discovered that mutations in the CFTR gene were responsible for causing CF. These mutations lead to a faulty or missing CFTR channel protein, which is important for controlling the movement of water and salt molecules in and out of cells. Consequently, thick and sticky mucus builds up in the body’s internal organs, driving CF symptoms.

Until about 10 years ago, the only available CF treatments aimed to ease symptoms, but did not target these underlying disease mechanisms.

Negulescu, Van Goor, and Hadida thus worked to develop CFTR modulators to address the underlying cause of CF by boosting CFTR functionality in various ways.

Based on their discoveries, Vertex currently markets four different modulator therapies, including Kalydeco (ivacaftor), Orkambi (ivacaftor/lumacaftor), Symdeko (tezacaftor/ivacaftor; sold as Symveki in Europe), and Trikafta (elexacaftor/tezacaftor/ivacaftor; sold as Kaftrio in Europe).

To develop these modulators, the trio of scientists and their teams had to test the effects of more than a million different compounds in human cells to identify the ones that might be candidates for clinical trials.

The development of Trikafta has been one of the most phenomenal and outstanding achievements of biomedical research in the last 30 years.

Patient community cheering on researchers to develop new CF therapies

“There was a lot of scepticism that this could be done,” Hadida said in a news story. “But the patient community was cheering for us.”

Each medication is approved for patients with CFTR mutations expected to be responsive to the treatment.

The triple combination therapy Trikafta is able to treat about 90% of people with CF who have eligible mutations, according to Vertex. It contains tezacaftor and elexacaftor, which work together to enable more CFTR protein to reach the cell surface, and ivacaftor, which helps the protein to remain open and function better. Trikafta is expected to drastically change the CF treatment landscape, increasing the life expectancy of CF patients from about 30 to more than 80 years.

“The development of Trikafta has been one of the most phenomenal and outstanding achievements of biomedical research in the last 30 years,” Francis Collins, MD, PhD, of the U.S. National Human Genome Research Institute, said in the news story.

“I hear almost every day from people who were really in trouble, with cystic fibrosis severely beginning to affect their chance of survival,” added Collins, who co-discovered that CFTR mutations were the cause of CF back in 1989. “Now, after going on Trikafta, they are back at work and thinking about what they might want to do for retirement.”

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Vertex also working on next-in-class triple-combo CFTR modulator therapy

Vertex is also working on developing a next-in-class triple-combination CFTR modulator therapy that contains vanzacaftor, tezacaftor, and deutivacaftor.

The therapy was found to improve lung function in CF patients in a Phase 2 trial (NCT03912233), and is now being evaluated in CF patients, 12 and older, in a pair of Phase 3 trials called SKYLINE 103 (NCT05076149) and SKYLINE 102 (NCT05033080). Another open-label Phase 3 trial (NCT05422222) is testing this combination in children with CF, ages 1-11.

Meanwhile, the company is also working with Moderna to develop a therapy called VX-522 that could treat the approximately 5,000 CF patients who don’t produce any CFTR protein at all, and who would not be expected to benefit from CFTR modulators.

A Phase 1 study (NCT05668741), which will evaluate VX-522’s safety, is currently recruiting nine adults with CF, ages 18-65, at sites in the U.S. and U.K. Eligible participants must have mutations that are not responsive to CFTR modulators.