FDA Grants Fast Track Status to Translate Bio’s RNA-Based Therapy MRT5005

The U.S. Food and Drug Administration (FDA) has granted fast track designation to MRT5005, an investigational RNA-based treatment for cystic fibrosis (CF), the therapy’s developer, Translate Bio, has announced.

Fast track is given to medications that aim to treat serious or life-threatening conditions and that have the potential to fill unmet medical needs to expedite their development and regulatory approval.

Clinical development programs that are granted fast track may be eligible for certain benefits, including additional meetings and communication with the FDA. And, if other criteria are met, they may also receive accelerated approval, priority review, and rolling review of a Biologics License Application.

MRT5005 is a first-in-class RNA-based therapy that works by delivering CFTR messenger RNA (mRNA) — the template cells use to make the CFTR protein that is faulty among those with CF — to cells in the lungs. The therapy is delivered to lungs via nebulization (inhalation of a mist).

By providing the correct instructions to make the CFTR protein to cells and directly addressing the root cause of the disease, MRT5005 is expected to work in all CF patients, regardless of the mutations they carry.

“MRT5005 has the potential to treat all people with CF, including those with mutations that result in limited to no CFTR protein production,” Ann Barbier, MD, PhD, chief medical officer of Translate Bio, said in a press release.

“The fast track designation will help Translate Bio to expedite the clinical development of this potentially transformative therapeutic,” she said.

In contrast, other therapies that aim to correct the defects of the CFTR protein to restore its function (i.e., CFTR modulators) are not universal. At present, about 10% of people with CF are expected not to benefit from currently approved CFTR modulators.

Preclinical data in animal models of CF has shown that MRT5005 can be delivered to the lungs by nebulization, leading to the production of the CFTR protein.

The investigational therapy is currently being evaluated in a Phase 1/2 trial (NCT03375047) called RESTORE-CF. The study aims to enroll at least 40 adults with CF, who will be randomly assigned to receive either a placebo or one of several doses (8–24 mg) of MRT5005 administered by nebulization.

The trial’s main goal is to assess the safety and tolerability of MRT5005. Effects on lung function (as measured by forced expiratory volume) will also be assessed.

Preliminary findings from the initial single-ascending dose portion of the trial, in which participants received a single administration of MRT5005 at three different doses (8, 16, and 24 mg), showed that those receiving MRT5005 at a dose of 16 and 24 mg experienced improvements in lung function.

Results of the multiple-ascending dose portion of the trial, in which participants will be treated once weekly for five weeks with different doses of MRT5005, are expected later this year.

RESTORE-CF, which is being conducted in collaboration with the Cystic Fibrosis Foundation Therapeutics Development Network, is currently recruiting participants at multiple locations in the U.S. Additional information is available here.