Is inhaled insulin finally within reach?

April 4, 2005

The Food & Drug Administration has accepted Pfizer and Sanofi-Aventis' new drug application for Exubera (inhaled human insulin powder). For the past 80 years subcutaneous injection has been the only route for delivering insulin to patients with diabetes mellitus, which affects over 17 million people in the United States. Insulin therapy is required for patients with Type 1 diabetes, and many patients with Type 2 diabetes will require insulin therapy either alone or as an adjunct to their oral medications. Lack of acceptance of continuous subcutaneous insulin delivery or multiple daily injections have been barriers to obtaining optimal HbA1c levels.

The Food & Drug Administration has accepted Pfizer and Sanofi-Aventis' new drug application for Exubera (inhaled human insulin powder). For the past 80 years subcutaneous injection has been the only route for delivering insulin to patients with diabetes mellitus, which affects over 17 million people in the United States. Insulin therapy is required for patients with Type 1 diabetes, and many patients with Type 2 diabetes will require insulin therapy either alone or as an adjunct to their oral medications. Lack of acceptance of continuous subcutaneous insulin delivery or multiple daily injections have been barriers to obtaining optimal HbA1c levels.

Exubera is insulin in the form of a dry powder that is inhaled into the lungs via an inhalation device prior to eating. Clinical trials have demonstrated that inhaled insulin is absorbed more rapidly and is cleared at a faster rate than human regular insulin injected subcutaneously. In a 24-week, open-label, parallel-group phase III study, 335 subjects were randomly assigned to receive either pre-meal inhaled insulin plus bedtime Ultralente or two or three injections of regular and NPH insulin. The primary endpoint was the change in HbA1c values. Mean decreases in HbA1c values were comparable for inhaled (8.1-7.9%) and conventional groups (8.1-7.7%). The researchers concluded that inhaled insulin is effective, well tolerated, and well accepted in patients with Type 1 diabetes and provides glycemic control comparable to that with a conventional insulin regimen. Initial concerns about Exubera's long-term pulmonary safety were addressed in several long-term studies that showed sustained glycemic control and pulmonary function in patients taking Exubera.

As part of a global agreement, Pfizer and Sanofi-Aventis will co-develop, copromote, and comanufacture Exubera. In addition, Pfizer is also working with Nektar Therapeutics, which developed the inhalation device and formulation.

At the 12th Conference on Retroviruses and Opportunistic Infections in Boston, GlaxoSmithKline presented new data supporting further evaluation of its HIV compound 873140, a cellular chemokine receptor (CCR5) antagonist being developed for the treatment of HIV infection. The CCR5 receptor is believed to be the predominant coreceptor used by the virus to enter and infect CD4 cells. According to GSK, 873140 selectively inhibits the binding of the HIV envelope to the CCR5 receptor.

The results from one study presented at the conference demonstrated that median CD4+ cell CCR5 receptor occupancy was 98% following seven days of dosing in eight HIV-negative subjects. In a dose-ranging study in 40 HIV-infected subjects, the median CD4+ cell CCR5 receptor occupancy was >95% across the doses. Higher doses tend to result in longer duration of occupancy. Additional studies are ongoing to determine the clinical effect of 873140 in the treatment of HIV/AIDS in combination with other antiretroviral agents.

The FDA has granted GSK fast-track designation for 873140 for the treatment of HIV infection.

Promising novel agent for Parkinson's Results from two recently published studies demonstrated that TEVA Pharmaceuticals' Agilect (rasagiline mesylate) may improve Parkinson's symptoms in patients already taking levodopa and may be similarly effective compared with entacapone (Comtan, Orion) in treating Parkinson's disease (PD).

Rasagiline mesylate is a selective, irreversible monoamine oxidase type-B (MAO-B) inhibitor that blocks the breakdown of dopamine. Clinical studies have shown that inhibitors of MAO-B, the main enzyme that metabolizes dopamine in the brain, can potentiate the beneficial motor effect of levodopa and attenuate motor fluctuations.

In the comparative trial, published in The Lancet, March 12, patients were randomized to rasagiline 1 mg once daily, entacapone 200 mg, with every levodopa dose, or placebo. Compared with placebo, both rasagiline and entacapone reduced mean daily off-time and increased daily on-time without troublesome dyskinesia (P < .001 for both).

Treatment with rasagiline 1 mg/ day in patients already on levodopa decreased the mean adjusted total daily off-time from baseline by 29% compared with 15% in the placebo group. The results from this randomized trial were published in the Archives of Neurology's February issue.