Kos Pharmaceuticals Inc announced successful results from a recently completed four-week, phase IIa human clinical trial evaluating Kos' inhaled insulin therapy for type 2 diabetic patients. Kos also announced that its KS 01-019 product under development is a combination of Niaspan and simvastatin, the second most widely prescribed statin worldwide for the treatment of dyslipidemia.

The New Drug Application (NDA) is projected to be submitted to the US FDA in 2006. The results of the phase IIa trial show that Kos' internally developed inhaled insulin formulation is comparable to the market leading injectable insulin in controlling blood glucose levels, while also reducing blood lipids such as LDL cholesterol and triglycerides, a release from company said.

Kos' inhaled insulin formulation also demonstrated bioavailability of up to 23 per cent in a previous phase I human study. The successful completion of these phase I and IIa studies support the safety and efficacy of Kos' patient-friendly, excipientfree formulation.

In the head-to-head comparative study of 24 type 2 diabetic patients, insulin-naïve patients were randomized to receive either Kos' inhaled insulin formulation at meals or a single evening injection of insulin glargine, a basal insulin analog marketed by Aventis Pharmaceuticals Inc. under the brand name Lantus, the release added.

Following a one-month treatment period, Kos' inhaled insulin formulation
demonstrated a mean reduction in mean blood glucose of 28 per cent, compared with a mean reduction of 23 per cent with insulin glargine. Kos' formulation also showed a trend toward greater improvement with respect to hemoglobin (Hb) A1c, showing a mean absolute reduction of 1.23 per cent, compared with a mean absolute reduction of 1.05 per cent with insulin glargine. The safety profiles of both treatments were comparable, with four mild to moderate hypoglycemic episodes occurring in both groups. Additionally, Kos' inhaled insulin formulation produced a 10 per cent reduction of LDL cholesterol at day 28, compared with an increase of 1.4 per cent with insulin glargine.

Similarly, triglycerides were reduced by 36 per cent with Kos' inhaled formulation, compared with a 12 per cent reduction with the injectable insulin. Such results are quite important in so far as many type 2 diabetics not only require good control of blood sugar, but also require modulation of abnormal lipids, which occur in more than 60 per cent of all diabetics.

"Injections have long been a hurdle in the treatment of certain patients with diabetes," said Jay Skyler, director of Endocrinology, Diabetes, and Metabolism, University of Miami. "A user-friendly inhaled insulin product will open the door for patients who have been hesitant to start therapy or comply with their current treatment," he added.

Kos' excipient-free formulation coupled with Kos' patented compact, hand-held Breath Actuated Inhaler (BAI) device offers a precision lung delivery platform for insulin therapy.

The Kos formulation contains no carriers or preservatives and incorporates a crystalline, recombinant human insulin (rh-insulin) delivered by a standard, well tested non-CFC, environmentally friendly propellant. In clinical testing, patients and physicians were impressed with the ease of use of the patented BAI delivery system in administering insulin therapy, potentially improving patient compliance. Both the excipient-free formulation and the BAI device were entirely developed internally by Kos. The Company is seeking a corporate partner to complete the clinical development of its innovative inhaled insulin product.

"We are extremely excited about the achievement of these important R&D milestones in both the solid dose and inhalation areas," Adrian Adams, president and CEO, Kos Pharmaceuticals Inc said adding, "Kos' inhaled insulin formulation is expected to confer highly potent and patient friendly insulin therapy that is well tolerated, possibly allaying side effects that have been observed with other preparations of inhaled insulin therapy. This formulation was designed to eliminate specific chemical additives, some of which have been associated with certain pulmonary side effects and have been cited as an issue with earlier generations of inhaled insulin. Further, this excipient-free, user-friendly technology is a product of our continued and measured investments in our inhalation platform, consisting of proprietary formulation and device technologies."