Translate Bio Announces Interim Results from Phase 1/2 Clinical Trial of MRT5005 in Patients with Cystic Fibrosis
-- MRT5005 was generally well tolerated at low and mid-dose levels; no serious adverse events reported at any dose level --
-- Marked increases in ppFEV1 (percent predicted forced expiratory volume in one second) observed after single dose of MRT5005, primarily at mid-dose --
-- Findings support exploration of two additional dose cohorts --
-- MRT5005 is the first mRNA therapeutic administered to patients for the treatment of a genetic disease --
-- Conference call today at
“Effectively delivering the desired mRNA sequence is an essential step to producing functional CFTR proteins. While some variability in ppFEV1 from day to day in CF patients is expected in a trial of this size, we believe that the observed improvements in ppFEV1 from baseline and the timecourse of the effect support a CFTR-related mechanism and may suggest that MRT5005 can enable the production of functional protein,” said
“Despite significant advances in the treatment of patients with CF, there remains a critical unmet need for patients whose genetic mutations are considered non-amenable to CFTR modulators,” said
Dr. Barbier continued, “On behalf of the team at
“These encouraging interim results represent a milestone in the mRNA development landscape as this is the first time an mRNA therapeutic has been evaluated for its potential to treat a genetic disease,” said Ronald Renaud, chief executive officer of Translate Bio. “Also, as the first inhaled mRNA therapeutic, these data indicate the potential of mRNA therapeutics for the treatment of lung diseases, and support the planned expansion of our earlier-stage programs based on this pulmonary delivery platform.”
Phase 1/2 Clinical Trial Results
Study Design and Baseline Characteristics Summary
The interim results summarize data from 12 adult patients with CF who received a single dose of either MRT5005 or placebo (3:1 randomization). Patients who received MRT5005 were assigned to one of three dose groups (8, 16 or 24 mg). Of the 12 patients, 11 had at least one copy of the F508del mutation and one patient did not have a F508del mutation and was considered non-amenable to CFTR modulator treatment. Seven of the 12 patients were taking an approved CFTR modulator through screening, dosing and follow-up.
Safety, Tolerability and Pharmacokinetic Summary
The most common adverse events through Day 29 were cough and headache. There were no treatment-emergent serious adverse events (SAEs). All treatment-emergent adverse events (TEAEs) were considered mild to moderate. Five patients, 3 of whom were in the 24 mg dose group, experienced transient, mild to moderate febrile reactions deemed related to study drug. These events occurred approximately 4-10 hours post dosing, and were characterized by fever and symptoms such as headache, fatigue, chills or nausea, which were treated with medicines such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), or an anti-emetic. Symptoms resolved within 24 hours, and all patients were discharged from the study center on Day 2 as planned. In these five patients, low levels of mRNA and/or lipid were detected in the blood.
|Characteristics through Day 29||MRT5005
|Overall Number of TEAEs reported||28||25||33||11|
|Number of Serious TEAEs reported||0||0||0||0|
|Number of TEAEs leading to discontinuation||0||0||0||0|
|Number of TEAEs resulting in death||0||0||0||0|
|Number of TEAEs classified as pulmonary exacerbation||0||0||2*||0|
|Number of TEAEs by Severity|
|* Occurred at Day 25 and Day 27|
Lung Function (ppFEV1) Summary
A primary measure of lung function, ppFEV1, was assessed at pre-defined timepoints throughout the trial. Patients in the pooled placebo group and the 8 mg dose group did not show a marked improvement in ppFEV1. In the eight day period after dosing, the three patients in the 16 mg dose group demonstrated maximal ppFEV1 increases of 11.1%, 13.6% and 22.2%, for a mean maximum increase from baseline (+/- standard deviation) of 15.7% (5.8). Of the three patients in the 16 mg dose group, two were on a stable CFTR modulator treatment regimen for at least 28 days, while the third had a genotype that is considered non-amenable to CFTR modulator treatments. Of the three patients in the 24 mg dose group, through Day 8, one patient experienced a maximum increase in ppFEV1 from baseline of 21.4%, while two patients did not show a marked increase in ppFEV1.
|Absolute Change from Baseline
Mean ppFEV1 % (SD)
through Day 8
ppFEV1 % (SD)
|Day 1 *||Day 2||Day 3||Day 8|
|8 mg||53.3 (7.2)||3.7 (0.9)||2.8 (1.8)||3.4 (2.3)||-1.2 (3.0)||4.4 (0.7)|
|16 mg||72.0 (6.6)||7.2 (7.3)||11.2 (10.3)||11.4 (5.1)||9.2 (1.8)||15.7 (5.8)|
|24 mg||79.2 (7.1)||2.5 (0.4)||8.6 (11.2)||6.6 (4.8)||2.3 (3.2)||9.7 (10.2)|
|Pooled Placebo||60.5 (18.5)||2.0 (3.8)||0.4 (2.4)||-0.2 (1.4)||-0.6 (4.0)||3.2 (2.7)|
|*8 hours post dose|
The Company anticipates presenting additional details from this interim data set at the
Phase 1/2 Clinical Trial Design
Based on the analysis of the SAD (Part A) interim results, the Company has proposed certain protocol changes in this ongoing Phase 1/2 clinical trial. In the SAD portion of the trial, the Company plans to amend the clinical trial protocol to include an additional 20 mg single dose cohort of four patients. In the MAD portion of the trial (Part B), the Company plans to amend the clinical trial protocol to add 12 and 20 mg dose cohorts with four patients each, the latter dosing cohort contingent on successful completion of the 20 mg single dose cohort and an acceptable safety profile in the lower MAD dose cohorts. The Company no longer plans to evaluate a 24 mg dose group in the MAD portion of the trial. The originally planned Part C of the clinical trial, which included bronchoscopies, is expected to be redesigned as a Part B expansion to instead focus on the enrollment of additional patients at dose levels of interest. As required, the Company plans to submit these protocol changes to the
The randomized, double-blind, placebo-controlled Phase 1/2 clinical trial of MRT5005 was designed to enroll at least 32 adult patients with CF who have two Class I and/or Class II mutations. After accounting for the planned protocol amendments, the Company expects to enroll up to 40 adult patients with CF. The primary endpoint of the trial is to assess the safety and tolerability of single and multiple escalating doses of MRT5005 administered by nebulization. Percent predicted forced expiratory volume in one second (ppFEV1), which is a well-defined and accepted endpoint measuring lung function, is also being measured at pre-defined timepoints throughout the trial. The Phase 1/2 clinical trial of MRT5005 for the treatment of CF is being conducted in collaboration with the Cystic Fibrosis Foundation Therapeutics Development Network.
MRT5005 is the first clinical-stage mRNA product candidate designed to address the underlying cause of CF by delivering mRNA encoding fully functional cystic fibrosis transmembrane conductance regulator (CFTR) protein to the lung epithelial cells through nebulization. MRT5005 is designed to treat all patients with CF, regardless of the underlying genetic mutation, including those with limited or no CFTR protein. MRT5005 has been granted Orphan Drug Designation in the U.S. and EU for the treatment of CF.
About Cystic Fibrosis
Cystic fibrosis is the most common fatal inherited disease in
Conference Call Information
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include, but are not limited to, those regarding: the potential for MRT5005 to address the underlying cause of CF, Translate Bio’s plans to continue to dose patients in its MAD portion of its Phase 1/2 clinical trial of MRT5005 and the expected patient enrollment size; the anticipated availability of the clinical data regarding MRT5005 in 2020; Translate Bio’s plans to amend the protocol of its Phase 1/2 clinical trial of MRT5005; the potential of mRNA therapeutics for the treatment of genetic disease, including diseases of the lung; Translate Bio’s plans to report additional details on the interim data set from its Phase 1/2 clinical trial of MRT5005; and Translate Bio’s plans, strategies and prospects for its business, including its lead development programs. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from current expectations and beliefs, including but not limited to: Translate Bio’s ability to advance the development of its platform and programs under the timelines it projects, demonstrate the requisite safety and efficacy of its product candidates and replicate in later-stage clinical trials any positive findings from preclinical studies or early-stage clinical trials; Translate Bio’s ability to enroll patients in its ongoing clinical trial; whether interim data from the Phase 1/2 clinical trial of MRT5005 will be predictive of the final results of that trial; the content and timing of decisions made by the
Source: Translate Bio, Inc.