In a mixed interim data drop, Arcturus Therapeutics has revealed a lack of efficacy for its investigational inhaled mRNA therapy in cystic fibrosis (CF).
The findings, shared today before market open, have sent the biopharma’s stock crashing, falling 55% from $23.16 per share to $10.44 per share as of midday.
In the ongoing open-label, multiple ascending dose phase 2 trial, six adults with Class I CF—which is when the condition is caused by a protein synthesis defect—received inhaled 10 mg doses of ARCT-032 daily for 28 days.
The trial is measuring forced expiratory volume in one second (FEV1), or how much air an individual can forcefully exhale during a single breath. The initial analysis comparing FEV1 values from the first day to Day 28 didn’t show any meaningful improvement, according to Arcturus.
Previously, management had set a 3% benchmark for FEV1 increase.
The FEV1 measure was a main focus for investors heading into the interim data readout, with the findings leaving “questions regarding the potential for sustained benefits in lung function from ARCT-032,” analysts at William Blair wrote Oct. 22.
That being said, the measure isn’t the study’s primary endpoint but instead a secondary one. The main goal of the trial is to measure the incidence and severity of adverse events (AEs), according to ClinicalTrials.gov.
In the same release, Arcturus pointed to the treatment’s generally safe and well-tolerated profile. Treatment-related AEs identified in a single-dose phase 1 trial were also seen in some participants for the first few doses, “but ceased with continued dosing,” according to the San Diego company.
The biopharma also highlighted reductions in mucus burden for four of the six patients, which William Blair analysts called “potentially promising.”
Arcturus is currently conducting a third stage of the trial that includes six participants receiving 15 mg doses. The biopharma then plans to launch a 12-week safety and preliminary efficacy study in up to 20 patients in the first half of next year.
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“We are particularly encouraged by the early signals of mucus plug reduction,” Arcturus Chief Medical Officer Juergen Froehlich, M.D., said in the release, citing the fact that Class I patients don’t produce cystic fibrosis transmembrane conductance regulator (CFTR) and therefore don’t respond to available CFTR therapy.
“Seeing a trend towards a reduction in mucus plugs and volume after only 28 days of treatment suggests biological activity,” Harm Tiddens, M.D., Ph.D., professor emeritus of pediatric pulmonology at Erasmus Medical Center in the Netherlands, said in the release. “Mucus plug reduction can be followed with longer-term lung function improvements over multi-month treatment durations.”
“These findings suggest that ARCT-032 may be addressing the underlying pathology of cystic fibrosis in a meaningful way,” he added.
For the upcoming study, analysts will be looking to see if longer treatment duration or higher dosing can improve efficacy signals beyond mucus clearance and cut down on data variability, according to William Blair.
Given the repeat dosing of Arcturus’ CFTR mRNA therapy, William Blair remains “somewhat optimistic” but reduced the probability of success for the program from 40% to 25%.
