An earlier RHI-based formulation known as Linjeta™ (and previously referred to as VIAject®) was the subject of a New Drug Application, or NDA, that we submitted to the FDA in December 2009. In October 2010, the FDA issued a complete response letter stating that the NDA for Linjeta™ could not be approved in its submitted form and that we should conduct two pivotal Phase 3 clinical trials with our preferred commercial formulation of Linjeta™ prior to re-submitting the NDA. The complete response letter included comments related to clinical trials, statistical analysis and chemistry, manufacturing and controls and tolerability issues relating to localized discomfort upon injection.
Based upon the complete response letter and subsequent feedback from the FDA provided to us at a meeting in January 2011, we decided to study newer RHI-based formulations in earlier stage clinical trials. Clinical trials of two newer formulations, BIOD-105 and Biod-107, did not demonstrate our target product profile. We subsequently conducted a Phase 1 clinical trial of two additional formulations, BIOD-123 and BIOD-125. In April 2012, we announced top-line results from this Phase 1 clinical trial of BIOD-123 and BIOD-125. In this clinical trial, BIOD-123 and BIOD-125 achieved our target pharmacokinetic, pharmacodynamic and toleration profiles. We now intend to study BIOD-123 in a Phase 2 clinical trial that we expect to begin in the third calendar quarter of 2012.
The Phase 1 clinical trial of BIOD-123 and BIOD-125 evaluated the pharmacokinetic, pharmacodynamic and injection site toleration profiles of these product candidates relative to Humalog®, a rapid-acting insulin analog. The objective of the clinical trial was to identify an RHI-based formulation with pharmacokinetic and pharmacodynamic profiles similar to the Linjeta™ formulation, but with improved injection site toleration characteristics. The 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.
In the Phase 1 clinical trial, absorption rates of BIOD-123 and BIOD-125 were significantly faster than that of Humalog® as indicated by 64% and 54% reductions, respectively, in mean times to half maximal insulin concentrations (p < 0.001 for both BIOD-123 and BIOD-125 compared to Humalog®). Both RHI-based formulations and Humalog®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, or VAS, 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).