- An experimental, messenger RNA-based treatment from Translate Bio failed to improve the lung function of patients with cystic fibrosis in an early-stage trial.
- The treatment, known as MRT5005, was the first of its kind to reach clinical testing, an inhalable therapy meant to use synthetic genetic material to treat the underlying cause of the disease. But while the drug was found to be largely safe, there was "no pattern of increases" in a key measure of lung function, the company said in a statement.
- The result is a setback for Translate and efforts to use mRNA for more than the vaccines the technology has become widely known for. But Translate isn't giving up, as CEO Ron Renaud said on a conference call the results provide a "data driven foundation" for a next-generation treatment.
Messenger RNA technology, which uses synthetic, genetic material to teach the body to make helpful proteins, has come of age over the past year.
When the coronavirus pandemic took hold in 2020, the technology was uniquely suited to meet the moment, having already shown potential as a new way to quickly design vaccines. The ensuing success of two similar mRNA vaccines from Moderna as well as partners BioNTech and Pfizer validated the technology, and the shots have since been used to protect millions of people around the world from COVID-19.
Efforts to use mRNA to make therapeutics, by comparison, are still in their infancy, with only a few programs for select diseases in human tests. The cystic fibrosis work at Translate Bio, whose platform originated within Shire years ago, is among the most advanced. "We recognized that we were entering uncharted territory" when clinical testing for MRT5005 began in 2018, Translate CEO Renaud said on a conference call Wednesday afternoon.
Translate aims to spray synthetic mRNA into cells in the lungs of cystic fibrosis patients so they'll produce a key protein known as cystic fibrosisTR. It's an ambitious plan with the potential way to treat all cystic fibrosis patients. And it's different from the approach used by Vertex, whose cystic fibrosis drugs help people who can already make some cystic fibrosisTR protein.
But it's also an unproven and complex therapeutic approach, in large part because of the challenge of getting mRNA into the lungs. Moderna and Vertex, for instance, have been working on a similar effort since 2016 and still don’t have a candidate near clinical trials. Upon forming a second cystic fibrosis alliance in 2020, Vertex chief scientific officer David Altshuler said delivering such treatments has proven "the most significant technological and scientific challenge."
Translate has been trying to overcome that hurdle by packing mRNAs into tiny fat bubbles known as lipid nanoparticles and then using a nebulizer to turn them into an inhalable mist. It’s been using that approach to develop medicines for cystic fibrosis and other lung diseases, such as pulmonary arterial hypertension. Initial results from a single dose of MRT5005 in cystic fibrosis patients showed some signs that the treatment might be having a positive effect.
Translate couldn’t build on those findings in a test of multiple doses of MRT5005, however. Without disclosing details, Translate said that while there were no severe safety problems, there was also "no pattern of increases" in a measure commonly used to assess lung function in cystic fibrosis patients.
Given the disappointing findings, SVB Leerink analyst Geoffrey Porges, on a conference call, asked whether Translate might abandon its work in lung diseases and focus on vaccines, a more proven approach. Translate already has several projects in the works through an alliance with Sanofi, including a coronavirus vaccine that began human testing last week.
But Translate executives saw promise in the cystic fibrosis trial. Researchers detected mRNA in the blood of some patients treated with MRT5005 — proof, Translate says, that multiple doses of an mRNA drug could be delivered to the lungs. Translate aims to tinker with various aspects of the approach, such as the lipid nanoparticles, the nebulization strategy and more, in the hopes of developing a more potent treatment for cystic fibrosis and other diseases.
"You're going to see us with more pulmonary clinical candidates," Renaud said. “This is really just the first stop for us on our journey to getting more therapeutics into the clinic."
Porges, in a research note, wrote that it’s "likely a 2-year endeavor" to bring a new cystic fibrosis drug to human testing. "It’s hard to give the company much credit for any value for the program," he wrote.
Translate shares fell more than 32%, to $17.38 apiece, on Thursday.