For the remaining 10% of patients with cystic fibrosis, no progress has yet been made

For the vast majority of cystic fibrosis patients, the new medications have been life-changing, transforming a debilitating lung disease into a manageable one.

But for about 10% of patients born with other genetic mutations, these treatments don’t work.

“We’ve been left behind,” said Emily Kramer-Golinkoff, who founded a nonprofit, Emily’s Entourage, to accelerate research into what she calls “the last 10 percent” of cystic fibrosis patients who don’t respond to current treatments or experience side effects.

As the cystic fibrosis community gathers this week in Atlanta for its largest annual gathering, Kramer-Golinkoff hopes these patients will play an important role in the conversation, especially after recent scientific setbacks. In May, Vertex and Moderna stopped a clinical trial of a drug using mRNA, the technology behind Covid vaccines, to treat the 10% of patients with cystic fibrosis, citing tolerability concerns. In February, drugmaker Boehringer Ingelheim ended a cystic fibrosis gene therapy trial.

More than four decades ago, when Kramer-Golinkoff was diagnosed with a progressive and fatal genetic disease at six weeks old, the story would have ended with a failed clinical trial. But today, thanks in large part to the work of his nonprofit, there are glimmers of hope.

Affecting approximately 40,000 Americans, cystic fibrosis causes a buildup of thick, sticky mucus in the lungs, creating life-threatening lung infections and respiratory failure. About 90% of patients with the disease have some genetic mutation and may benefit from Trikafta and a newer version, Alyftrek, both made by Vertex Pharmaceuticals. By improving the function of a protein called CFTR that maintains the balance between salt and water in the body, the drugs thin the mucus in the patient’s lungs. A 2024 article in The Atlantic, titled “The Cystic Fibrosis Breakthrough That Changed Everything,” describes how these patients can now run up stairs and participate in 1o-K races.

But for patients like Kramer-Golinkoff who don’t produce fully functional CFTR protein to benefit from these drugs, the big breakthrough hasn’t changed much.

Since its inception 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 presents a particularly difficult scientific problem, because the lung is an organ designed to keep things out. To add to this challenge, a CF patient’s lungs are filled with mucus.

“It’s incredibly difficult with a healthy lung,” said Chandrabali Ghose, chief science officer of Emily’s Entourage. “But it’s much more difficult in a CF lung.”

A promising gene therapy developed by Spirovant Sciences could work regardless of a patient’s genetic mutation. The drug is currently in an early-stage clinical trial.

Emily’s Entourage is also investing in other approaches – phages, which are natural viruses that kill bacteria, and antimicrobials – to treat drug-resistant infections that can ultimately be fatal for CF patients.

“We see this as a time-saving initiative,” Ghose said.

The foundation’s work could ultimately help patients suffering from other conditions, including those suffering from joint and skin infections. His group also funds research into nonsense mutations, which are changes to DNA that cause cells to stop producing proteins sooner than they should, thereby causing disease. What scientists learn from this research could be relevant to patients with various rare genetic diseases.

“We all benefit from a leap forward,” Kramer-Golinkoff said.

Kramer-Golinkoff sees hope in Baby KJ’s story, which has sparked regulatory changes aimed at allowing scientists to develop tailor-made drugs for individual patients. There are approximately 2,000 genetic mutations responsible for cystic fibrosis. Many are extremely rare and only affect a small handful of people.

Perhaps its biggest challenge is combating the misconception that cystic fibrosis is curable, which stifles investment in new treatments.

“A lot of people hear about the progress that 90% of the CF community is making and think we have it figured out, but that’s not true,” Kramer-Golinkoff said. “Those in the remaining 10% are still dealing with the same deadly disease that cystic fibrosis has always been. »

Now 41, Kramer-Golinkoff is grateful to be alive. Most CF patients at this stage die or receive a lung transplant. But his life is not easy. She takes antibiotics to control chronic infections in her lungs, takes supplemental oxygen 24 hours a day, injects herself with multiple injections for cystic fibrosis-related diabetes, and takes more than 30 pills — all to save her remaining lung function and delay the progression of the disease.

She knows that she is not unique and that it is important not to forget this group of patients who are still waiting for their big medical breakthrough.

“There are a lot of other people in the same boat as me,” she said. “We don’t have time to wait.”

CNBC Cures is underwritten by Alexion, AstraZeneca Rare Disease.