For the Final 10% of Cystic Fibrosis Patients, the Breakthrough Still Hasn’t Come

For most cystic fibrosis patients, new drugs have been life-changing, transforming a debilitating lung disease into a manageable condition. The disease affects about 40,000 Americans and causes thick, sticky mucus to build up in the lungs, creating life-threatening lung infections and respiratory failure. About 90% of patients have a certain genetic mutation and can benefit from Trikafta and a newer version, Alyftrek, both made by Vertex Pharmaceuticals. The drugs improve the function of a protein called CFTR that maintains the balance of salt and water in the body, thinning mucus in the lungs. A 2024 article in The Atlantic headlined “The Cystic-Fibrosis Breakthrough That Changed Everything” described how those patients can now run up stairs and take part in 10-K races.

But about 10% of patients are born with other genetic mutations, and the treatments do not work for them. “We have been left behind,” said Emily Kramer-Golinkoff, who founded the nonprofit Emily’s Entourage to speed research for those patients, who either do not respond to current treatments or experience side effects. Kramer-Golinkoff was diagnosed with cystic fibrosis at six weeks old more than four decades ago, when a failed clinical trial would have been where the story ended. Today, she and her organization are pushing for more options.

The recent setbacks have made that work more urgent. In May, Vertex and Moderna stopped a clinical trial of a drug that used mRNA, the technology behind the Covid vaccines, to treat patients in the 10%, citing tolerability issues. In February, the drugmaker Boehringer Ingelheim ended a trial of a gene therapy for cystic fibrosis. Kramer-Golinkoff hopes the final 10% will be a major part of the conversation at the Atlanta gathering.

Since its creation in 2011, Emily’s Entourage has raised more than $22 million and funded 51 research projects developing multiple therapeutic approaches, including antisense oligonucleotides, or ASOs, small molecules and gene therapies. Delivering a drug to the right cells is especially difficult because the lung is designed to keep things out, and the lung of a cystic fibrosis patient is filled with mucus. “It’s incredibly challenging in a healthy lung,” said Chandrabali Ghose, chief scientific officer for Emily’s Entourage. “But it’s orders of magnitude more difficult in a CF lung.”

One promising gene therapy developed by Spirovant Sciences could work regardless of a patient’s genetic mutation, and it is now in an early-stage clinical trial. Emily’s Entourage is also investing in phages, naturally occurring viruses that kill bacteria, and antimicrobials to treat drug-resistant infections that can ultimately be fatal for cystic fibrosis patients. “We see these as buying-time initiatives,” Ghose said. The foundation is also funding research into nonsense mutations, changes in DNA that cause cells to stop making proteins earlier than they should, causing diseases. What scientists learn could be relevant to patients with a range of rare genetic conditions. “We all benefit when there’s a leap forward,” Kramer-Golinkoff said.

Kramer-Golinkoff sees hope in the story of Baby KJ, which has spurred regulatory changes aimed at allowing scientists to develop custom-made drugs for individual patients. There are about 2,000 genetic mutations that cause cystic fibrosis, and many are extremely rare, affecting just a small handful of people. She said her biggest challenge is combating the misconception that cystic fibrosis has been cured, which stifles investment into new treatments. “Many people hear about the progress for 90% of the CF community and think we’ve figured it out, but that is not true,” Kramer-Golinkoff said. “Those in the final 10% are still contending with the same killer disease that CF has always been.”

Now 41, Kramer-Golinkoff is grateful to be alive. Most cystic fibrosis patients at her stage are dying or receive lung transplants. Her life is not easy: she is on antibiotics to control chronic infections in her lungs, takes supplemental oxygen around the clock, injects multiple shots for diabetes related to cystic fibrosis, and takes more than 30 pills, all to salvage what lung function she has left and delay progression of the disease. She knows she is not unique and says it is important not to forget the patients still waiting for their medical breakthrough. “There are a lot of other people in the same boat as me,” she said.