By Lisa Seachrist
Amarillo BioSciences Inc.'s first Phase III clinical trial of oral interferon alpha (IFNalpha) showed the drug could enhance saliva production in patients suffering from Sjogren's syndrome.
The 250-patient study demonstrated a statistically significant increase in patients' unstimulated whole saliva (UWS) production. However, that measure was a secondary endpoint. The primary endpoint - a measure of stimulated saliva production - showed improvement, but failed to reach statistical significance.
As a result, the Amarillo, Texas-based company has decided to change the primary endpoint of its ongoing second stage Phase III clinical trial to UWS production and use the stimulated saliva production as a secondary endpoint.
"We feel this is a very reasonable change because the unstimulated whole saliva production is the most important endpoint for improving dental health," said Kathleen Kelleher, chief operating officer for Amarillo. "There is precedent for changing endpoints with the FDA."
Sjogren's syndrome is an autoimmune disorder that attacks the moisture-producing glands in the body leaving patients with a dry mouth and dry eyes. Sjogren's also can damage the kidneys, blood vessels, lungs, liver, pancreas and brain. Sjogren's affects 2 million to 4 million Americans, 90 percent of whom are women.
The dry mouth can be so severe patients may have difficulty eating and talking. As a result of the dry mouth, patients are at risk for periodontal disease and other dental complications.
Alpha interferon is a critical immune system modulator. High dosage injections of the drug currently are approved to treat patients with cancer, multiple sclerosis and hepatitis. Amarillo is developing the low dose oral formulation for Sjogren's, fibromyalgia, Behcet's disease, hepatitis B, hepatitis C and opportunistic infections in HIV-infected patients.
One of the ways that oral IFNalpha may help in Sjogren's is to stymie the disease process. If so, it would be the first treatment for Sjogren's to have an effect beyond ameliorating symptoms.
In the Sjogren's study, patients were treated three times daily with lozenges containing 150 international units of IFNalpha or a placebo. When the company analyzed the data using all patients who completed the trial, they found both stimulated and unstimulated saliva production increased. However, the FDA typically requires an intent-to-treat analysis, which includes all patients enrolled in the study regardless of whether or not they completed the study. In that analysis, only the unstimulated whole saliva production demonstrated a statistically significant increase.
"We had a hard time keeping everyone in the study. The drop out rate was much higher than we expected," Kelleher said. "Part of the problem may have been the fact this is a long study."
The study lasted 6 months, and the second Phase III study of 250 patients is equally long. Kelleher said the company remains quite positive about the drug.
"We are very excited about our results," Kelleher said. "We're the first folks to show you can give interferon alpha as a low dose lozenge and have an effect."
In order to change the endpoint, the company only needs to inform the FDA of its intention to do so.
Amarillo's stock (OTC BB: AMAR) closed Friday at $2.875 a share, down 87.5 cents.