Biodel initiates phase 2b trial of ultra-rapid-acting BIOD-531 in type 2 diabetes – May 21, 2015

This morning, Biodel announced the initiation of a phase 2b trial of its lead insulin candidate BIOD-531 (U400 ultra-rapid-acting human insulin), consistent with previous guidance indicating that the study would begin in 2Q15. The open-label trial (ClinicalTrials.gov Identifier: NCT02446028) aims to enroll 130 patients with type 2 diabetes and daily insulin requirements of 40-200 units who will be randomized to receive twice-daily doses of either BIOD-531 or Lilly’s Humalog Mix 75/25 for 18 weeks. The primary endpoint will be change in A1c from baseline at 18 weeks; postprandial glucose excursions, change in weight, and hypoglycemic event rates are all secondary endpoints. Biodel has expressed particular interest in the postprandial glucose endpoint, as this is where the company believes BIOD-531 will have an advantage over existing premixed and concentrated insulins. Primary completion is expected in June 2016, and topline results should be available by mid-2016.

Biodel has framed this trial primarily as a “dress rehearsal” for phase 3 studies, which are expected to begin in mid-2016. As a reminder, Biodel originally planned to conduct a single phase 3 trial of BIOD-531 in patients with type 2 diabetes and moderate-to-severe insulin resistance but announced in its F4Q14 update that it had added a trial in type 1 diabetes in response to feedback from the FDA. The phase 3 trials will have a similar design to the phase 2b study but with a larger sample size (~500 patients in each study). Ultimately, the company sees the target population for BIOD-531 as quite broad, though management has indicated that Biodel will likely focus its own commercialization efforts on severely insulin resistant patients and pursue a partnership to target a wider spectrum. We agree that BIOD-531 is one of the company’s most exciting assets and believe it could hold fairly broad appeal. However, the unmet need is certainly greatest among patients with severe insulin resistance, for whom Humulin U500 (which has a substantially slower action profile compared to its U100 counterpart) is essentially the only existing option. Of course, there is always plenty of regulatory uncertainty when it comes to diabetes drug development, particularly for insulins (see: Complete Response Letters for Biodel’s Linjeta [an earlier rapid-acting insulin formulation], Novo Nordisk’s Tresiba [insulin degludec], and MannKind’s Afrezza [inhaled insulin]), and we hope that Biodel’s frequent communication with the FDA will prevent any unpleasant surprises.

• Biodel has completed two phase 2a trials of BIOD-531 in type 2 diabetes showing impressive prandial and basal control with the potential for flexible dosing. The first trial in moderately insulin-resistant patients demonstrated superior postprandial glycemic control and higher time in range with pre-meal or post-meal BIOD-531 vs. both Humalog Mix 75/25 and Lilly’s Humulin R U500 given pre-meal. The second trial in severely insulin-resistant patients demonstrated superior control vs. Humalog Mix 75/25 and comparable control vs. Humulin R U500 over a 24-hour period. In terms of postprandial control, pre-meal BIOD-531 was superior to both comparators given pre-meal, and post-meal BIOD-531 was equivalent to both comparators given pre-meal. Results from this trial will be presented as a poster (92-LB) at ADA in June. The potential for post-meal dosing could be one of the product’s strongest selling points, as it aligns with how many patients dose their prandial insulin in a real-world setting.

-- by Emily Regier, Adam Brown, and Kelly Close