MRT5005 Gets FDA Rare Pediatric Disease Status as Adult Trial Faces Delay Due to COVID-19

Translate Bio‘s therapy MRT5005 has been given a rare pediatric disease designation by the U.S. Food and Drug Administration (FDA) for the treatment of cystic fibrosis in children, while its ongoing clinical trial investigating the therapy in adult patients faces delays due to the COVID-19 pandemic, the company has announced.

The designation is given to aid in the development of treatments for rare diseases (affecting fewer than 200,000 people in the U.S.) that primarily affect patients up to 18 years old.

Cystic fibrosis (CF) is caused by mutations in the CFTR gene, which codes for an essential protein called cystic fibrosis transmembrane conductance regulator (CFTR) that allows the transport of ions into and out of cells. In CF patients, the CFTR protein is defective or not produced at all.

MRT5005 is an inhaled therapy, administered via nebulizer directly to the lungs, that delivers mRNA molecules that provide instructions to produce a functional CFTR protein (mRNA is the genetic blueprint for protein production; the “messenger” that carries coding information from DNA).

Thus, MRT5005 has the potential to treat all patients with CF, regardless of their underlying genetic mutation.

The FDA granted MRT5005 its fast track designation in February to expedite the therapy’s development and approval process.

“More than 75% of people with CF are diagnosed by age 2 — as such, we are pleased to receive the FDA’s Rare Pediatric Disease designation for MRT5005 for the treatment of CF, and we are planning future trials of MRT5005 in pediatric CF patients,” Ann Barbier, MD, PhD, chief medical officer of Translate Bio, said in a press release.

“This important designation underscores the significant unmet medical needs for people living with cystic fibrosis who are still waiting for life-saving treatments, and the potential role that MRT5005 could play in treating patients who are not amenable to current treatment options,” she added.

However, Translate Bio is anticipating that MRT5005’s clinical development will be delayed due to the pandemic caused by COVID-19, especially in its ongoing Phase 1/2 RESTORE-CF trial (NCT03375047) testing the therapy in adult patients with CF.

As SARS-CoV-2, the virus causing COVID-19, infects the respiratory system, CF patients are considered to be at a higher risk for severe illness according to the Centers for Disease Control and Prevention. To avoid putting CF patients at risk, Translate Bio is expecting that the dosing and follow-up measures of the RESTORE-CF trial will be delayed.

“Our priority is always patient safety and well-being, and specifically during this unprecedented public health crisis, we join our health and local authorities, healthcare providers, and patient advocacy groups in ensuring that patients with CF exercise an abundance of caution to prevent exposure to SARS-CoV-2,” Barbier said.

“As more patients with CF and their physicians choose to avoid unnecessary risk of exposure to SARS-CoV-2, we, like many companies across the healthcare and biopharmaceutical industry, anticipate that patient dosing and follow-up visits in our ongoing trial will be affected,” she added.

RESTORE-CF is a placebo-controlled, double-blind Phase 1/2 trial planning to enroll at least 40 adult patients to assess the safety, tolerability, and efficacy of MRT5005. The trial is split into two phases, with patients initially receiving a single dose of varying strength (single ascending dose phase) or a placebo, followed by a phase in which patients receive multiple ascending doses, once per week for five weeks.

In July 2019, Translate Bio shared preliminary data, collected from 12 patients in the single dose phase, which showed “promising” results in improved lung function in patients treated with MRT5005.

The RESTORE-CF trial is being conducted at 17 sites across the U.S.

“We are in regular communication with our clinical trial sites to monitor the impact of COVID-19, and to continue to provide the best possible care and support to the patients in the trial,” Barbier said. “Given the uncertain and dynamic nature of this situation, we will provide an update when we have additional insight into enrollment and dosing metrics.”

The trial was originally estimated to conclude in December 2021.