Why Biodel Is Breathing Easy, Part 1

by: Joseph Krueger
As a direct result of all my recent research considering MannKind's (NASDAQ:MNKD) Afrezza, I came accross a company who is innovating the management of diabetes through insulin better than Mannkind. This insulin innovation is not from the dominant players in the business (Novo Nordisk (NYSE:NVO), Sanofi Aventis (NYSE:SNY) or Eli Lilly & Company (NYSE:LLY)), but from a startup company based in Danbury, Connecticut called Biodel, Inc (BIOD).
This insulin innovation is not as sexy as Mannkind's Afrezza inhaled insulin, but does directly address a much needed problem in the effective use of insulin by diabetics. Using their proprietary delivery technology platform, Biodel is seeking FDA approval for a rapid acting injectable insulin called VIAject. In my (and Biodel's) opinion, VIAject will solve the deficiencies in existing insulin therapeutic approaches while not introducing potential new ones like Afrezza does.
Existing fast acting insulin products are designed to deliver the appropriate glucose control at mealtime. However, the absorption of existing fast-acting insulin injectables is still too slow to mimic the natural initial insulin spike - a problem Afrezza was designed to address (apart from needle-free administration). Like Afrezza, VIAject delivers insulin in a manner which more closely resembles the way a normal body uses insulin to function, diminishing hyperglycemia and hypoglycemia swings that currently marketed insulin's cause.
VIAject, like Afrezza, acts quickly because it prevents the formation of six-molecule aggregates (hexamers), which delay insulin absorption. Like Afrezza, VIAject's design causes rapid dissolution of the hexameric form of insulin to the monomeric form when it is administered. Like Afrezza, this allows more rapid delivery of insulin into the blood to produce its desired biological effects.
The similarities between Afrezza and VIAject are no coincidence- Biodel's founder is Solomon Steiner, the inventor of Technosphere, which is the technology behind the monomeric delivery of insulin by Afrezza. Steiner continued to work on Technosphere until Pharmaceutical Discovery Corporation was purchased by Al Mann and renamed Mannkind. Mannkind pursued the inhaled insulin route and Biodel pursued the injected insulin route, both setting out to solve the problem of slow insulin absorption with current injectable (even fast-acting) insulins.
According to data provided by Biodel at the 2010 JP Morgan Health Conference, the competing rapid-acting insulins (Novolog from Novo Nordisk, Aprida from Sanofi Aventis and Humalog from Eli Lilly & Company) all have relatively similar pharmacokinetic profiles, with maximal absorbtion of insulin being reached 45-60 minutes after injection.
In contrast, VIAject reaches 80% maximal absorption in 15 minutes (100% at 30 minutes); quite similar to Afrezza's 15 minute maximal absorption profile. In contrast, the other fast acting insulins, such as Humalog, reach only 20% maximal absorption at 15 mins and 100% at 45 minutes. In essence, VIAject offers a similar PK profile to Afrezza, giving similar short term glucose control as Afrezza does, filling the void left by injectable competitors.
On December 30, 2009, Biodel submitted a New Drug Application (NDA) for FDA approval to market VIAject for meal-time use by people with Type 1 or Type 2 diabetes (to be used in a manner similar to Afrezza). This NDA was based upon results two pivotal 6-month Phase 3 clinical trials comparing VIAject to Humalog in patients with Type 1 and Type 2 diabetes, as well as interim results from the long-term, 18-month safety extension trials for patients who completed the pivotal Phase 3 clinical trials.
In these clinical trials, Viaject not only demonstrated equivalent long term glucose control (hA1c levels), but also improved secondary measures of glucose control, such as faster reductions in blood-glucose activity, reduced risks of hyperglycemia and hypoglycemia, and less weight gain than patients who received the competing fast acting insulin. These are all claims that Afrezza has touted as well.
Although Afrezza's proponents are touting the secondary benefits in short term glucose and less hypoglycemia events, as discussed in my previous article, these differences are not significant enough to mitigate the potential labelling and use risks of Afrezza. In contrast, VIAject does not carry any pulmonary risks, labeling risks, use risks, or marketing risks as it is administered by injection like the current fast acting insulins.
Given the similarity in pharmacokinetic profile between Afrezza and VIAject, it is not surprising that VIAject touts identical benefits to Afrezza, as this is the key component that determines how VIAject improves glucose control.
A perhaps yet unrecognized safety benefit of VIAject, as this study shows, is that VIAject requires one third to one half the dose of insulin required compared to fast acting injectable (3-6U VIAject vs 12U injectable) and one fifth the dose of Afrezza (3-6U VIAject vs 15-30U Afrezza). Thus, beyond equivalency to Afrezza, VIAject offers potential safety and use benefits over Afrezza by reducing the amount of insulin used.
In contrast to analysts and investors having controversial opinions about the likelihood of Afrezza's approval, VIAject is expected by analysts to be approved without significant delay. Unlike Afrezza, VIAject is comprised of commercially available recombinant human insulin and a proprietary formulation of ingredients, all of which are Generally Regarded As Safe (GRAS) by the FDA.
Since VIAject is simply a modified form of recombinant human insulin, Biodel is submitting its new drug application for VIAject under section 505(b)(2), which governs the review of an NDA for a modified form of a previously approved product. This allows Biodel to submit an NDA based on published literature or on the FDA's finding of safety and efficacy of one or more previously approved drugs. This route typically allows approval of a drug based on fewer clinical or nonclinical studies than would be required under a full NDA. Because of this, its likely to encounter less scrutiny than Afrezza, which is filed as a new drug under section 505(b)(1).
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