Cystic fibrosis patients changed the future of the disease — can celiac disease emulate their success?

March 29, 2022

Cystic fibrosis patients banded together and changed the future for those living with the disease. Can increased patient participation produce similar results for celiac disease?

By Maria Luci, Director of Research Engagement

In November 2019, the drug Trikafta was approved by the Food and Drug Administration to treat cystic fibrosis (CF)—an inherited and deadly lung disease. The new drug was found to be highly effective at treating the debilitating illness. Prior to this landmark therapy, many CF patients had no approved drugs to manage their symptoms, which led to early death. Trikafta and ensuing breakthroughs have changed the future for CF patients. Once a death sentence, new therapies have shifted CF into a manageable condition for many. 

The Need for Therapies in Celiac Disease 

For Beyond Celiac the hope is that similar breakthroughs can be accomplished for celiac disease. While celiac disease and cystic fibrosis are very different disorders, there are important lessons to be learned by looking to the Cystic Fibrosis Foundation and how they’re overcoming major hurdles in the development of desperately needed therapies. 

Currently, the only treatment for celiac disease is a gluten-free diet. No pharmaceutical interventions or therapies are available. Yet, research shows that one in five children with celiac disease isn’t healing on the gluten-free diet and up to 30% of adults continue to have symptoms. There are also a number of patients suffering from refractory celiac, a severe form of the disease that doesn’t respond to the diet. Refractory celiac disease can lead to total incapacitation and a rare form of cancer. 

While it is true that for the majority of patients with celiac disease, their condition is manageable through the diet, this management is accomplished through a strict, lifelong diet change that many describe as isolating and burdensome. 

Considerable numbers of celiac disease patients find that controlling their disease takes such extraordinary lengths that it seriously impacts their quality of life, says gastroenterologist Dan Leffler, MD, and Senior Medical Director at Takeda Pharmaceuticals, a company actively looking at methods to treat celiac disease. 

“People shouldn’t have to choose a college or a career based on their having celiac disease, and they do now,” he says, adding that this burden is not something we expect people with other diseases to undertake. “Every community deserves a personalized approach and a choice, and that’s not something we’ve been able to provide to people with celiac disease today. But hopefully, in the future, we will.”

Looking to Cystic Fibrosis for Inspiration

Douglas Jacobstein, MD, a gastroenterologist and Vice President of Clinical Development at Provention Bio, believes in the real need to create better lives for those with celiac disease. He says that “currently there are no approved pharmacotherapies for celiac disease and despite the use of the gluten-free diet following diagnosis, up to half of all celiac patients continue to have symptoms.” Provention Bio is currently recruiting for their phase 2b study evaluating the use of the monoclonal antibody PRV-015/ordesekimab to help treat those still suffering from symptoms of celiac disease on the diet.

Jacobstein agrees that we can and should look to cystic fibrosis for inspiration. “The CF Foundation model is a great one to emulate. Having the full support of patient support groups is critical to the success of any trial moving forward in celiac disease,” he says. The same methods that helped make CF a more manageable disease can be utilized to help patients living with celiac disease.

Robert Beall, PhD, led the Cystic Fibrosis Foundation during its first impressive sprint toward therapies. Their organization paved the path forward for life-saving treatments by creating a Research Development Program and a Therapeutics Development Program; making crucial partnerships with researchers, biotech, and pharma; and by getting patients involved in research and building relationships with the patient community. They also invested heavily in research and went headfirst into venture philanthropy, funding pharmaceutical endeavors. 

During Beall’s tenure, the CF patient community raised millions of dollars for research which the foundation then fed into clinical pursuits. Patient participation, through funding and clinical trial participation, was crucial to getting CF therapies off the ground. Their combined efforts lead to more than doubling the life expectancy of those with cystic fibrosis. For the first time, more than 50 percent of those with cystic fibrosis are older than 18 years of age. The condition was no longer classified as a pediatric disease. 

In a 2020 Washington Post article, Beall was described as incredibly impatient by Francis Collins, who had been a scientist studying cystic fibrosis at the University of Michigan. Collins and his lab team eventually discovered the gene related to cystic fibrosis. 

Beall joined the Beyond Celiac board in 2017 to help move the needle in a similar fashion for celiac disease. Beyond Celiac has since created a Science Team, a strategic plan toward therapies and a cure, and began partnering with pharmaceutical companies, academia, and biotech to accelerate trials and research through recruitment, grants, and data collection.

A key takeaway from Beall is that we need to be impatient and we need to work together to make miracles happen. People with celiac disease have been patiently waiting decades for advancements and the time is now to make them happen. Ultimately though, pharmaceutical companies and researchers can’t move forward without two particularly necessary things: funding and patient participation. Both have been somewhat lacking in celiac disease.

Opportunities for Patients in Research

When patients think about participation in research they often automatically conjure visions of sterile hospitals and needles. This is an outdated portrait of what research really means today. Clinical trials are very different today than they were in the past, with patients being active participants in the research and having fully informed consent. 

However, while clinical trials are an incredibly important piece, it is still just a part of the whole puzzle. There’s a spectrum of involvement in research, with some requirements as low as filling out a simple survey. An easy way to get involved is to join the patient registry Go Beyond Celiac which, like that of Cystic Fibrosis Foundation, collects important information about living with celiac disease before, during, and after diagnosis. Patient stories can help drive data through this collective online study that brings researchers closer to real treatments and a cure. 

There are also a variety of research studies that do not involve medications or therapies of any kind. Massachusetts General Hospital, MassGeneral Hospital for Children, and the Celiac Program at Harvard Medical School are jointly looking at babies at-risk for celiac disease to determine how the disease develops and ways to prevent it. Enrolled participants are known as GEMM Babies, and results are already beginning to be disseminated. Participants’ parents received the latest updates on learnings in 2020, which included that cesarean delivery, antibiotics at birth, and formula feeding were seen to cause gut changes linked to immune system dysfunction in infants at-risk for celiac disease.

“I was super excited. I thought, ‘Oh my gosh, we will finally get to see some results,” said Theresa Moutafis, who was pregnant with her daughter, who is now 7, when she enrolled her in the study.

In the UK, research looking into potential brain damage related to gluten exposure by scientists at the University of Sheffield caught the eye of Beyond Celiac, who awarded them an Established Investigator Grant to continue their study utilizing MRIs and other tools to assess neurological manifestations of gluten-related disorders.

In 2020, DOGGIE Bag Study findings from Boston Children’s Hospital concluded that two-thirds of patients who were strictly following a gluten-free diet still showed signs of having consumed gluten.

There are numerous studies like these looking into how celiac disease works, how it is diagnosed, who is at risk, and its effects — and they all require patient participation to continue their crucial work. 

The Importance of Clinical Trials

While joining registries and participating in non-clinical studies are important, clinical trial participation is essential to move therapies and a cure forward. There are a number of trials currently working to recruit celiac disease patients, including the 9 Meter’s CedLara Study, Provention Bio’s Proactive Study, and ImmunogenX’s Solutions for Celiac Study. Anokion’s ACeD Study has recently been able to move ahead after recruiting sufficient participants. They are now pushing on to the next phase in the clinical trial process. Beyond Celiac played a role in recruiting for these trials. Other potential treatments are also in development

Despite the great need, it can be a struggle for celiac disease trials to recruit participants. Patients often have concerns and misperceptions about trials. Jacobstein says that “opportunities to participate in clinical research [for celiac disease] have been limited, creating a lack of understanding of how clinical research works.” However, he adds, “in order for advancements to be made, we need the involvement of the entire celiac community. Their willingness to lend their time to research is critical to the success of these studies.”

One of the most common concerns patients express is if a trial will require a “gluten challenge” — meaning ingestion of gluten during the study. Leffler says this is one of the major barriers to recruitment because the risks of ingesting gluten have been ingrained so well in patients that they believe they will suffer long-term consequences if they participate in gluten challenge trials. However, he says, “short-term gluten exposure, when monitored by a clinician, is very different than long-term exposure in the real world when you’re not [monitored].” He acknowledges that some patients may not feel great, but that the exposures are safe in a trial.

Leffler also brings up that there is an upside to gluten exposure as a trigger for celiac disease. Unlike trials in other diseases, such as rheumatoid arthritis, you often can’t truly be sure if the drug worked or if the disease simply waned or went into remission. With celiac disease, he says, “we can be sure that at the end of the day that this drug protects you from this much gluten.”

Jacobstein mentions that a number of myths he’s encountered during the recruitment process include that patients won’t be able to keep seeing their own doctors and that they won’t have access to their results or know if they received the treatment or placebo at the end of a trial. But Jacobstein says that one of the biggest misconceptions is that participating in a clinical trial is unsafe. He states, “investigational drugs undergo several steps to make sure as best as possible that they are safe. In addition, patients are continually monitored during a study and after the treatment ends for any side effects. These side effects are tracked not only by your research doctor but by the sponsor to make sure there aren’t any signals indicating abnormal responses to the treatment.”

“Everyone is honestly a little hesitant to sign up for a trial, it’s natural,” says Leffler. But he points to major overhauls in recent years to empower patients and that almost all of them he encounters come out happy they participated. He suggests a “silver lining” of Covid-19 is that now more trials offer some in-home and telemedicine options, allowing for easier participation. He says that at Takeda they work with patient organizations and their own patient advisory group to design trials and continue to ask for input all the way through, making sure the patient’s voice is heard and that they feel in control while participating in a trial. 

Thanks to the participation of celiac disease patients, several drugs are now mid-trial, including CeDLara, which is in Phase 3 trials. However, more patients are needed to join trials to truly accelerate treatments and a cure. 

“You have to have the end in mind,” Leffler says, “this is for a better future.”

Be an Impatient Patient

Cystic fibrosis patients worked together to change their future; celiac disease patients can do the same. Now is the time for patients to band together and get involved in accelerating research. If studies don’t have funding or participants, they can lag, stop, or end with inconclusive results. Leffler says that trials are “already designed to use the minimal number of people they need. If you can’t get enough you’re left with uncertain results.” This leads to confusing outcomes, little scientific progress, and may even discourage future research into the disease. Those with celiac disease should follow the cystic fibrosis model and become impatient patients today — by actively participating in trials, studies, and donating to research — to create a better future tomorrow.

Learn more about participating in clinical trials for celiac disease here

In our continued pursuit of treatments and a cure, Beyond Celiac will host our third Research Summit in April. This event will bring together Beyond Celiac-funded researchers, clinician-scientists, patients, drug developers, patient advocacy leaders, and more to discuss the past, present, and future of celiac disease research. Sign up for Research News emails to stay up to date on the latest celiac disease research and for findings and updates from our Summit. 

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