Also working on noninjectable insulin is Biocon, which last year landed Bristol-Myers Squibb (BMS) as its partner to partially fund Phase II trials of its IN-105 outside India for two years. After that, BMS has the option to assume full responsibility for IN-105, including all development and commercialization activities outside India—in return for BMS paying Biocon a license fee, milestone payments, and royalties on IN-105 sales outside India.
Oramed in July enrolled its first patient in a Phase IIa trial assessing the safety of ORMD-0801, an orally ingestible insulin capsule on patients with type 2 diabetes. A total 30 patients will be enrolled.
“Results of the trial are anticipated by the end of the calendar year,” Aviva Sherman, an Oramed spokeswoman, told GEN.
ORMD-0801 is also under study in a clinical trial in Israel in August that began recruiting patients with type 1 diabetes, for which -0801 is envisioned as a complement to injections, allowing fewer daily injections.
In September, Oramed submitted a pre-IND package to FDA for its ORMD-0901 (oral exenatide), a GLP-1 analog for type 2 diabetes. “By acting on multiple fronts, i.e., stimulation of insulin release and suppression of glucagon release, as well as other actions, GLP-1 addresses diabetes-related glycemia issues on a broader level than does exogenously administered insulin,” Sherman said.
Oramed said its oral insulin mimics insulin's natural location and gradients in the body by traveling through the gastrointestinal tract encapsulated, then releasing the insulin in the small intestine, from which it is ferried to the liver via the portal vein. The first-pass metabolism significantly reduces the risk of hypoglycemia, the most common side effect of injected insulins.
Novo Nordisk’s candidate OI362GT or NN1954, an oral basal insulin analog intended as a tablet treatment, generated successful results from a single-dose Phase I trial earlier this year. Peter Kurtzhals, svp in diabetes research at Novo Nordisk, told GEN NN1954 is delivered through enteric coated tablets targeting the duodenum, facilitated by the rise in pH that occurs when a substance passes from the acidic milieu in the stomach into the intestine.
“The delivery in duodenum is not more porous, but contents of the gall fluid secreted here may play a role in facilitating absorption of some substances from this part of the gut,” Kurtzhals said.
NN1954 absorption is enabled via partner Merrion Pharmaceuticals’ GIPET® technology. GIPET uses specifically designed oral formulations of patented absorption enhancers designed to activate micelle formation, facilitating transport of drug and increasing absorption.
The drug and enhancer are not bound to each other chemically, but are both ingredients of the tablet, with no interaction between active pharmaceutical ingredient and absorption enhancer. Co-release of the drug and absorption enhancer occurs following dissolution of the coating and a general disintegration of the tablet.
“The oral insulin project is currently in Phase I clinical development. Contingent on successful outcome of these trials, Phase II will be initiated within 1–2 years,” Kurtzhals said.
By the time Novo Nordisk and Oramed complete their required additional trials, followed by formal regulatory reviews, MannKind may have already delivered the first noninjectable insulin to grateful diabetics. Or not. FDA can be expected to show particular caution with noninjectable insulin candidates, given the problems inhalables have had in recent years. To win approvals, companies will have to show not only the usual safety and efficacy, but that their products are better than past noninjectable candidates—drugs young Leonard Thompson could only dream about when he took insulin by needle and made history nearly a century ago.
When you do think the FDA will approve a noninjectable form of insulin?
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