Moving forward in their collaboration to market an inhaled insulin product, Aradigm Corp. and Novo Nordisk A/S began a Phase III program for NN1998, the AERx insulin Diabetes Management System (iDMS).
The first study, in Type I diabetics, is designed to show that the long-term safety and efficacy profile of inhaled human insulin is comparable to that of subcutaneous injections. The two-year, multicenter, open-label trial will study patients receiving either inhaled insulin via the AERx system or subcutaneous injections of NovoRapid (NovoLog in the U.S.) three times daily before meals. Both groups also are receiving basal insulin once or twice daily.
In addition to investigating long-term pulmonary safety, the 300-patient study also will examine the incidence of hypoglycemic events, insulin antibody formation, blood glucose profiles and overall treatment satisfaction. Positive results from the non-insulin-producing patient cohort could be a boon for the compound.
"If you can demonstrate a level of control in the Type I patient, then you are virtually guaranteed to see that same level of control in a Type II patient, since they're an easier population to deal with," Aradigm President and CEO Richard Thompson told BioWorld Today. "[Type I] represents a more sensitive population, and therefore the FDA and other regulatory agencies have asked us to look very closely at that group."
In total, the program will enroll about 1,500 patients worldwide, though Hayward, Calif.-based Aradigm did not disclose further details of the upcoming studies.
The compound and its delivery system have proved successful in previous studies. Late last year, the companies released results of a 12-week, 100-patient Phase IIb study that showed the AERx iDMS to be at least as effective as intensified, subcutaneous injections of insulin in people with Type II diabetes.
At the American Diabetes Association meeting in June, the partners further detailed clinical results, which showed comparable glycemic control between patients using the AERx system and those using injections. Results also pointed to a favorable safety profile for the AERx system, including no difference between the two groups in FEV1, a lung function parameter. The number of hypoglycemic events was 151 in the AERx group compared to 211 in the comparator group.
Results may vary among Type I patients, though.
"The concern if you did overdose or underdose is greater in [Type I] patients because they have no ability to adjust naturally," Thompson said. "So you might see more hypoglycemia if patients are not getting an accurate dose."
But the system is designed with a highly accurate dose in mind. The AERx electronic platform guides users to inhale correctly and automatically deliver the drug at the right time.
"We use a liquid-formulated drug that is basically the same as the injectable form," Thompson said. "What is really unique about the AERx technology is that we use a disposable strip that has the insulin filled into it, and in that strip is a disposable nozzle that creates the aerosol."
Patients place the pre-filled insulin strip into the device, select the proper dose on a screen located on the device and then inhale. The device uses colored lights to guide a patient's rate of inhalation, and then delivers the aerosolized liquid at the right time.
"It's almost impossible to do it incorrectly because of the breath control," Thompson said. "They always get high-quality aerosol because of the built-in nozzle - we've virtually eliminated the possibility of patients making errors while they're taking their insulin."
Thompson said his company is responsible for product development, manufacturing and delivery. He said Copenhagen, Denmark-based Novo is taking over responsibility for all further clinical trial costs, and would gain worldwide commercial marketing and sales rights for the resulting product.
He did not disclose a revenue-sharing arrangement with Novo, which has made about $30 million in equity investments in Aradigm. Novo's 20 percent ownership stake in Aradigm makes it Aradigm's largest stockholder.
The two companies first entered a potential $50 million deal in 1998 to develop the inhalable AERx iDMS. Last fall, Novo made a $20 million investment in Aradigm at the same time the companies first disclosed the Phase IIb data. (See BioWorld Today, Oct. 26, 2001.)
Aradigm's shares (NASDAQ:ARDM) fell 28 cents Tuesday to close at $2.70.