FDA clears next phase of RCT2100 clinical trial for cystic fibrosis
Study to assess lung function, patient-reported outcomes with mRNA therapy
The U.S. Food and Drug Administration (FDA) has cleared the start of the third part of a Phase 2 clinical trial testing RCT2100, Recode Therapeutics’ investigational treatment for cystic fibrosis (CF).
This portion of the Phase 2 trial (NCT06237335) will test RCT2100 together with Kalydeco (ivacaftor) in people with CF who are either not eligible for CFTR modulators or are not taking them. Enrollment is underway at sites in the U.S., with study locations in the European Union and U.K. expected to open in early 2026.
“Advancing the study of the combination of RCT2100 with ivacaftor [Kalydeco] represents an important milestone for the program and for patients,” Shehnaaz Suliman, MD, Recode’s CEO, said in a company press release. “This study will provide further insight into the potential additive benefits of RCT2100 when combined with ivacaftor on clinically meaningful measures such as lung function and patient-reported outcomes.”
How RCT2100 aims to address the root cause of CF
CF is caused by mutations in the CFTR gene, which lead to a defective or absent CFTR protein that is key to the regulation of mucus production. Without enough working CFTR protein, thick, sticky mucus builds up in the lungs and other organs, causing many CF symptoms.
CFTR modulators are medicines that help improve the function of the CFTR protein in people with specific disease-causing mutations. But not everyone with CF can benefit from modulators — either because their mutations don’t respond, or because they cannot tolerate these medications.
RCT2100 is an inhaled therapy that uses Recode’s lipid nanoparticle platform to deliver CFTR messenger RNA (mRNA) directly to lung cells. This enables production of a functional version of the CFTR protein. mRNA is a temporary molecule with genetic code that serves as a template for protein production.
According to Recode, RCT2100 is being developed to treat the 10% to 15% of people with CF whose mutations do not respond to CFTR modulators or who cannot take these therapies.
Earlier trial stages tested safety and dosing of inhaled mRNA therapy
The first part of the trial is evaluating RCT2100’s safety in healthy volunteers, who receive single ascending doses of the therapy compared with a placebo. The second part is testing RCT2100 in adults with CF, ages 18 to 60, who cannot take CFTR modulators, given as multiple ascending doses for up to 12 weeks
In the third part, researchers will assess the safety and tolerability of RCT2100 when given together with Vertex Pharmaceuticals‘ Kalydeco. Participants will first take Kalydeco alone for two weeks, then receive RCT2100 together with Kalydeco over a four-week period. Up to 12 people with CF will take part. Secondary measures will evaluate lung function and quality of life.
This results of this combination regimen will be compared with Kalydeco alone. According to Recode, the findings will help inform the development and optimization of the RCT2100 treatment regimen.
Recode’s development of RCT2100 has been supported by an additional $3 million investment from the Cystic Fibrosis Foundation. The CF Foundation had previously invested $15 million to support early RCT2100 development, as well as $15 million more to fund the development of gene-editing therapies for CF.
RCT2100 has received FDA orphan drug designation, a status that supports the development of treatments for rare diseases that affect fewer than 200,000 people in the U.S. This status provides regulatory benefits like tax breaks, fee waivers, and the potential for seven years of market exclusivity if the therapy is ultimately approved.
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