Status: Treatment IND granted in Sept. 2009

Organizations involved:

Generex Biotechnology Corp. – Manuf.; R&D; Tech.; World mark.

Sanofi S.A. – Manuf.

Eli Lilly & Co. – Former

PMG Pharma – Latin Amer. mark.

Cross ref.: See the Insulin Products entry (#630).

Description: Oral-lyn is aqueous liquid-based formulation of recombinant E. coli-expressed regular insulin packaged for buccal or oral spray administration, with the insulin absorbed into the body through the lining of the mouth using the Company's proprietary RapidMist device. It is cited as "a safe, simple, fast, effective, and pain-free alternative to subcutaneous injections of prandial insulin and is conveniently delivered to the membranes of the oral cavity by a simple asthma-like device with no pulmonary (lung) deposition... As a pain-free and convenient method of insulin delivery, Generex Oral-lyn™ will allow individual patients to "fine tune" and then maintain their metabolism resulting in an improved quality of life. Accordingly, Generex Oral-lyn™ provides the opportunity for the establishment of a new and more efective diabetes treatment paradigm."

Generex's buccal delivery technology, RapidMist, is comprised of a proprietary formulation and a proprietary device. The formulation is aerosolized with a pharmaceutical grade chemical propellant and is administered to the patient using the proprietary RapidMist device. This is a small, lightweight, hand-held, easy-to-use aerosol applicator comprised of a container for the formulation, a metered dose valve, an actuator and dust cap. Using the device, the patient self-administers the formulation by spraying it into the mouth. The device contains multiple doses, the number being dependent, among other things, on the concentration of the formulation. Absorption of insulin occurs in the buccal cavity, principally through the inner cheek walls. RapidMist's features and claimed benefits include needle-free, pain-free technology (non-invasive); rapid onset of action; no lung deposition (absorption in the buccal mucosa); established safety profile (FDA approved excipients); precise dose control (meeting USP guideline); expected improvements in compliance; easy self-administration with a convenient to carry and handle small device.

Nomenclature: Insulin, rDNA/buccal [BIO]; Oral-lyn [TR]; Oralin [TR former]; Oral Recosulin [SY]; insulin, recombinant, buccal (oral)

Companies.: Oral-lyn was developed and is manufactured and distributed by Generex Biotechnology Corp. In 2000, Generex entered into a collaboration with Lilly for development and worldwide marketing of Oral-lyn. In June 2003, this agreement was terminated, as Generex began testing Oralin in a Phase IIb trial. Generex and a number of other manufacturers worldwide.

Sanofi manufactures and supplies recombinant human insulin crystals to Generex Biotechnology for use in Oral-lyn commercial production.

In Dec. 2009, Oral-lyn was commercially available in India, Lebanon, Algeria and Ecuador and Phase III type 1 diabetes trials were ongoing at several sites.

In Sept. 2010, Generex granted exclusive development and marketing rights in Chile to PMG Pharma S.A.

In Oct. 2010, the Generex Web site reported that "Generex seeks to out-license its RapidMist product programs and identify in-licensing opportunities and acquisitions in the areas of diabetes...[and various other Indications:]."

FDA class: Drug NDA

Approvals: Date = 20090910; Treatment IND (not a real approval)

Status: In late 2007, Generex received approval of Oral-lyn in India. On March 26, 2009, t he Drugs Controller General (DCGI), India, revoked approval of Oral-lyn in India, because the insulin spray had not been tested in local/indigenous human clinical trials.

On Sept. 10, 2009, FDA granted Oral-lyn a Treatment IND protocol. Oral-lyn is provided to patients with serious or life-threatening Type 1 or Type 2 diabetes mellitus with no satisfactory alternative therapy available for the treatment of diabetes, and who are not eligible to participate in the Company’s ongoing global Phase III pivotal clinical trial. There are no oral or injectable medications contraindicated for this IND program. [FDA’s Treatment IND program allows companies to provide early access to investigational therapeutics for patients with serious or life-threatening conditions for which there is no satisfactory alternative treatment. Therapeutics that are granted approval by the FDA for the Treatment IND program must demonstrate the likelihood of efficacy through clinical testing. FDA rules permit companies to recoup costs associated with granting expanded access to unapproved drugs, but companies are prohibited from marketing or generating any profits while operating under Treatment IND approvals.].

In March 2010, the Treatment IND was expanded to include adminstration by licensed and qualified Nurse Practitioners (in the 11 states granting authority to Nurse Practitioners to issue prescriptions to patients without medical doctor collaboration).

At the time of its Treatment IND approval, Oral-lyn had received approval in Ecuador, and was approved for sale in India in Oct. 2007.

Trials: In clinical studies so far, Oral-lyn "has been shown to be very efficacious."

In Oct. 2010, a global Phase III clinical trial with Oral-lyn for Type-1 and Type-2 diabetes was underway in the U.S., Canada, Russia, The Ukraine, Romania, Bulgaria and Poland.