CHICAGO — an investigational drug for influenza that targets a host-cell factor necessary for infection reduced viral loads by more than 100-fold in a randomized trial, a researcher said here. an inhalable fusion protein called DAS181 reduced viral loads by 2.38 log10 relative to placebo on day five after symptom onset in the 297-patient trial (P=0.008), according to Roy Steigbigel, MD, of the State University of New York at Stony Brook. three days of once-daily treatment led to decreases in viral loads of 1.01 log10 on day two and 1.46 log10 on day three relative to placebo (both P<0.01), Steigbigel told attendees at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). Action Points  

• Note that this study was published as an abstract and presented at a conference. these data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
• Explain that an investigational drug for influenza that targets a host-cell factor necessary for infection reduced viral loads by more than 100-fold in a randomized trial.
• Note that the drug studied, an inhalable fusion protein called DAS181, targets sialic acid, a receptor on airway cells to which the flu virus’s hemagglutinin protein binds.

However, elevations of alkaline phosphatase were seen in most patients receiving the drug but only rarely in the placebo group, Steigbigel said. the same signal was seen in preclinical studies with DAS181 and is apparently the result of systemic exposure to the drug, causing reduced clearance of the enzyme.

DAS181 targets sialic acid, a receptor on airway cells to which the flu virus’s hemagglutinin protein binds. This is the process that allows the virus to enter host cells and begin replicating.

The drug combines a sialidase enzyme molecule with an anchor protein attaching the drug to cell surfaces so that its effect is prolonged.

Steigbigel reported results from an international phase II trial conducted across three flu seasons in the northern and southern hemispheres.

Patients were 18 to 68 years old and were enrolled within 48 hours of symptom onset, with confirmation of flu infection by a standard rapid test.

They were assigned to three double-blind treatment groups: three doses of placebo; DAS181 given as a single 10-mg dose on the first day, followed by two daily placebo doses; or three daily doses of 10 mg DAS181.

Excluding patients who didn’t receive the assigned doses, there were 88 patients in each group.

The single dose of DAS181 was only slightly more effective than placebo for the major study endpoints, which included time to decreased viral shedding as well as viral loads in gargle washes.

But the three-dose regimen was significantly superior to placebo for both endpoints.

Decreased viral shedding was assessed as the time from baseline to a 1-log10 decrease in viral burden in gargle washes. among patients receiving three daily doses of DAS181, it was achieved in a median of two days, compared with four days for the placebo group.

Steigbigel said the study was not powered for clinical efficacy endpoints, and he did not report on whether the drug shortened time with symptoms.

He did indicate, though, that use of acetaminophen for symptom relief was more frequent in the placebo group.

Session co-moderator Laurent Kaiser, MD, of the University Hospital of Geneva in Switzerland, questioned whether the deactivation of sialic acid receptors could create increased opportunities for bacterial infection.

Some research had suggested that pneumococcal bacteria might be better able to infect airway tissue in the absence of sialic acid.

Steigbigel responded this had been a concern with DAS181 and was examined in animal studies, which found no evidence of increased susceptibility to such infections.

“The proof of the pudding will be in the clinical data,” he added. the phase I and phase II studies had so far not revealed any increased risk, Steigbigel said.

At a separate press briefing, Kaiser said DAS181 was one of several promising new anti-flu agents in the development pipeline.

He noted that, currently, the only drugs specific for flu are inhibitors of the virus’s neuraminidase enzyme.

“We will have soon, hopefully, other drugs than the neuraminidase inhibitors to target influenza and to open the possibility of combined therapy for severe cases,” Kaiser said.

The study was funded by the National Institute of Allergy and Infectious Diseases. DAS181 is under development by NexBio.

Steigbigel declared he had no relevant financial interests. all other investigators on the study were NexBio employees.