Phase 2 Trial Evaluates DAS181 for Parainfluenza Virus in Immunocompromised Patients

Parainfluenza viruses are commonly associated with causing respiratory illnesses in infants and young children, but the viruses can also infect adults, leading to severe infections and potential morbidity and mortality.

In a presentation at ID Week 2018 in San Francisco, California, Roy Chemaly, MD, MPH professor of medicine, University of Texas MD Anderson Cancer Center, presented an Oral Abstract Session about a phase 2 trial assessing the effects of DAS181—a sialidase fusion protein—and its activity in immunocompromised patients including stem-cell and solid-organ transplant patients with parainfluenza virus lower respiratory tract infections.

In an exclusive interview with Contagion^®, Dr. Chemaly discussed the burden of parainfluenza virus in immunocompromised patients and the mechanism of action of DAS181 (see video).

“DS181 is a new drug under development with a specific mechanism of action. First, it is given in aerosolized form and the way it works is it is an entry inhibitor; it will cleave the sialic acid on the cell, preventing entry of the virus into the cell—and not only parainfluenza but also influenza and maybe other viruses,” Dr. Chemaly explained.

The phase 2 trial was a randomized, double-blind trial that enrolled 110 patients who had been diagnosed with parainfluenza virus lower respiratory tract infections and required supplemental oxygen. Patients enrolled in the trial included hematopoietic cell transplant recipients (74 patients), hematological malignancy/solid tumor patients on chemotherapy (29), and lung transplant recipients (7).

The participants were randomized 2:1, stratified by mechanical ventilation at baseline, to received nebulized FAS181 (4.5mg in a 3.5 mL/day) or placebo for up to 10 days. The investigators indicate that the primary endpoint was the proportion of patients reaching clinical stability survival (CSS) at day 45. In this trial, CSS was defined as alive, resolution of supplemental oxygen, and normalization of vital signs.

At day 45, CSS was achieved by 39.2% of the patients in the DAS181 treatment group and 31.4% of placebo (p=0.29), and the proportion among non-mechanically ventilated patients was 45.0% vs. 31.0% (difference -14.0%, p=0.15), respectively.

Dr. Chemaly discussed the phase 2 trial, including the outcomes of the study with Contagion^® (see video).

“The drug did not meet the primary endpoint of clinical stability survival rate at day 45, but we learned a lot from this trial,” Dr. Chemaly elaborated, “We learned that not every patient needs to be treated for parainfluenza…When we did the sub-group analysis we found that stem-cell transplant patients, within a year of their transplant, DS181 was much better than placebo, compared to…1 year after transplant.”

The median change in nasopharyngeal parainfluenza virus infection viral load by day 10 and median hospitalization days was -1.44 vs. -0.68 log₁₀ (p=0.51) and 13.5 vs. 21 days (p= 0.10) for DAS181 and placebo, respectively, according to the study abstract. Furthermore, the mean absolute increase from baseline FEV1% predicted was 16.82 for DAS181 vs. 2.02 for placebo (p =0.001).

The post-hoc analysis on the probability to return to room air (RTRA) suggested that DAS181 reduced the need for supplemental oxygen in the non-MV stratum after day 21 (p=0.09). hematopoietic cell transplant recipients within 360 days from transplant had a 40.8% treatment effect on RTRA at day 28 (p= 0.04) and 36.7% on mortality at Day 45 when compared to placebo (p= 0.06).

The occurrence of adverse events was reported to be similar in both treatment groups. Day 45 all-cause mortality was comparable in both groups (32.4% DAS181 vs. 31.4% placebo).

Dr. Chemaly summarized the need for effective antivirals and treatment options for parainfluenza viruses to Contagion^® and how patient populations including immunocompromised patients as well as infants and elderly patients with comorbidities (see video).

“There are no treatment options available, either for prophylaxis or for therapy; so there is no vaccine and no drug available as of today for this virus,” Dr. Chemaly remarked.

The abstract concludes that DAS181 was well tolerated overall and demonstrated a signal for clinical efficacy in the patient population. Additionally, DAS181 was granted breakthrough therapy designation for the treatment of parainfluenza virus lower respiratory tract infections in immunocompromised patients and will be assessed in a phase 3 trial in the future.