Biodel Inc., focused on the development and commercialization of innovative treatments for diabetes, has reported positive top-line results from a phase I clinical trial of its product candidates, BIOD-123 and BIOD-125 -- two proprietary ultra-rapid-acting formulations of recombinant human insulin (RHI).

BIOD-123 and BIOD-125 achieved the company's target pharmacokinetic, pharmacodynamic and toleration profiles in a phase I clinical trial; BIOD-123 favoured as lead product candidate to advance to phase II.

Projecting initiation of a phase II clinical trial of BIOD-123 in the third calendar quarter of 2012.

Continuing development of ultra-rapid-acting insulin analog-based formulations with selection of candidates and initiation of a phase I clinical trial projected in the second half of calendar year 2012.

Liquid glucagon formulation for use as a rescue treatment for patients experiencing severe hypoglycemia projected for NDA submission in the fourth calendar quarter of 2013 or first calendar quarter of 2014

The phase I clinical trial evaluated the pharmacokinetic, pharmacodynamic and injection site toleration profiles of BIOD-123 and BIOD-125 relative to Humalog, a rapid-acting insulin analog. The objective of the trial was to identify an RHI-based formulation with pharmacokinetic and pharmacodynamic profiles similar to the company's previous Linjeta formulation used in phase III clinical trials, but with improved injection site toleration characteristics. The phase I clinical trial was a single-center, randomized, double-blind, three-period crossover trial in 12 patients with Type 1 diabetes. Each study drug was administered subcutaneously on separate days with a washout period between injections.

Pharmacokinetic measurements were made using separate assays to quantify the active ingredients in the study drugs — RHI in the case of BIOD-123 and BIOD-125 and insulin lispro in the case of Humalog. The clinical trial was powered to measure differences in time to half maximal insulin concentrations. Pharmacodynamic measurements were assessed using the euglycemic clamp method.  Local injection site discomfort was measured with a 100 mm visual analog scale (VAS) and patient questionnaires.

In the phase I clinical trial, absorption rates of BIOD-123 and BIOD-125 were significantly faster than that of Humalog as indicated by 64 per cent and 54 per cent reductions, respectively, in mean times to half maximal insulin concentrations (p < 0.001 for both BIOD-123 and BIOD-125 compared to Humalog). In a previous clinical trial, the Linjeta formulation demonstrated a 61 per cent reduction compared to Humalog. Peak metabolic effects were not significantly different between the three study drugs.

All three were well tolerated, with injection site tolerability generally perceived by patients to be similar to that of their usual mealtime injections used at home.  As measured on a 100 mm visual analog scale in which 100 mm is defined as the worst possible injection discomfort, local toleration was not significantly different for BIOD-123 compared to Humalog (BIOD-123 mean VAS 3.6 +/- 2.1 mm, Humalog 1.8 +/- 1.1 mm, p=NS). The VAS score for BIOD-125 was slightly higher as compared to Humalog (mean VAS 6.8 +/- 2.9 mm, p < 0.05). However, this score was markedly improved relative to the Linjeta formulation, which had a mean VAS of 22.0 +/- 2.8 mm in a previous study.

Dr Alan Krasner, Biodel's chief medical officer, stated, “Biodel's previous Linjeta formulation demonstrated a desirable ultra-rapid absorption profile, but had challenges with respect to local injection site toleration.  The goal of our subsequent formulation development has been to maintain the ultra-rapid absorption profile of Linjeta, while improving injection site toleration. These recent data suggest that our latest formulations have achieved this goal, and we feel that further clinical development is warranted.”

Dr Errol De Souza, Biodel's president and chief executive officer, stated: “The findings from these studies are very encouraging and will enable us to advance an ultra-rapid-acting RHI-based formulation into a phase II clinical trial as early as next quarter. In parallel, we will continue our development of ultra-rapid-acting insulin analog-based formulations, with the goal of advancing product candidates into a phase I clinical trial later in 2012. We expect our ultra-rapid-acting insulin program, along with our liquid glucagon rescue programme that is targeted for NDA filing by the end of 2013 or early 2014, to generate multiple meaningful milestones in the short-term.”