Aradigm Corp. and Novo Nordisk A/S met primary safety endpoints in the interim analysis of the Phase III trial of their inhaled insulin, but there was bad news, too: The drug delayed post-meal plasma glucose suppression in Type I diabetics, and Novo said it will end the trial early.
"They're more difficult to treat [than Type II diabetics], but it was a surprise," said Richard Thompson, president and CEO of Hayward, Calif.-based Aradigm.
Aradigm's shares (NASDAQ:ARDM) dropped 29.7 percent, ending Friday at $1.23, down 52 cents.
"We're looking forward to a rebound at some point, when people fully understand the story," Thompson told BioWorld Today.
Type II patients in earlier Phase II trials with NN1998, otherwise known as the AERx insulin Diabetes Management System, had shown satisfying post-meal glucose profiles. Results from the Phase III trials of Type I diabetics, though, show glucose levels right after meals were higher than those in patients given subcutaneous insulin. At night, levels were lower than those in trial participants given the subcutaneous form.
Type I patients are regarded as more sensitive than Type II diabetics, so the Phase III trial was designed to include them. Another factor that might be blamed for the outcome is that patients in the subcutaneous group got a newer, faster-acting insulin, called insulin aspart, while AERx patients were given regular human insulin.
"That is definitely a high standard to go for," Thompson said. "Only about 30 percent of patients taking mealtime insulin use that form. But the position of Novo is that, if you can't match the gold standard, you have to keep trying."
Patients with Type I diabetes, previously known as "juvenile diabetes," make up a small percentage of the overall market, he noted.
"We have equivalent data to this with Type II patients, and in those studies we do hit the mark," he said. A recent change in diagnostic criteria shows 41 million Americans are at risk for Type II diabetes, with more than 16 million already having the disease.
Novo said it will finish the study in the next few weeks, giving patients about 19 months of maximum exposure to the drug, rather than the originally planned 24 months.
Is another trial in the offing?
"We're not sure yet," Thompson said, noting that the set of data will be studied further. "We know what it's telling us, but we don't know why it's telling us that," he added.
Bagsvaerd, Denmark-based Novo has promised an update in August, "but that doesn't mean it couldn't be sooner," Thompson said.
Meanwhile, he found cause for encouragement in the Phase III trial's meeting of primary safety endpoints, with no change in pulmonary function tests and no adverse effects reported from examinations of chest X-rays. Antibody production, while expected to increase in the AERx group due to the new route of administration, led to no adverse clinical outcomes. And the main efficacy endpoint of the trial - levels of HbA1c, a subtype of hemoglobin A - proved statistically the same in the AERx and subcutaneous groups.
"The market has in the past been very sensitive on safety in this product category," Thompson noted. Aradigm and Novo entered the potential $50 million deal in 1998, and finished Phase IIb trials several years later. (See BioWorld Today, Nov. 21, 2001.)