Medical Device Daily Contributing Writer

NEW YORK – The Rodman & Renshaw (New York) annual Global Investment Conference drew a standing-room-only crowd to the New York Palace Hotel last week during a period of financial uncertainty.

The program led off with a featured presentation by former President Bill Clinton, who emphasized the need to repair the ailing economy and the need for healthcare reform.

About 360 companies, including many private and development-stage companies made presentations, with specialty pharmaceutical companies representing the dominant category. These firms use a wide range of drug-delivery technologies.

A look at some of the categories and companies involved in the 10th annual conference:

Insulin delivery for diabetics

MannKind (Valencia, California) continues to actively pursue inhalable insulin, despite the departure of other firms that have abandoned the pulmonary delivery of insulin. The therapy consists of a proprietary dry powder formulation of insulin (Technosphere) that is inhaled into the deep lung using an inhaler. The pH-sensitive Technosphere particles immediately dissolve upon contact with the lung surface, releasing insulin monmers that rapidly enter the bloodstream

MannKind recently completed the first of three pivotal Phase III clinical trials using Afresa, its rapid-acting human insulin. The study was conducted on Type 1 diabetic patients and compared the safety and efficacy of prandial inhalations of Technosphere insulin vs. prandial subcutaneous injections of insulin. Afresa yielded comparable reductions in A1C levels, superior fasting blood glucose levels and better early post-prandial glucose control.

The company also is evaluating in a Phase III trial the use of Technosphere insulin alone and in combination with metformin in patients with Type 2 diabetes who are not achieving desirable glucose control with a combination of metformin and sulphonylurea.

Generex Biotechnology (Toronto) is conducting a global Phase III trial of Oral-lyn, an insulin spray for use as an alternative to subcutaneous injections of prandial insulin in the treatment of Types 1 and 2 diabetes. The company's RapidMist inhaler delivers a precise dosage of a drug to the lining of the mouth (buccal delivery) and not to the lungs.

Generex is collaborating with Fertin (Vejle, Denmark) in the development of metformin gum for Type 2 diabetics. The company also is developing fentanyl and morphine sprays for pain management, using its RapidMist device.

Oramed (Jerusalem, Israel) is developing an oral dosage form of insulin based on its proprietary drug delivery technology. A Phase IIa clinical trial of its oral insulin capsule has been completed and demonstrated that the product was effective in lowering blood glucose levels in patents with Type II diabetes. Phase IIb trials are scheduled to begin in India in early 2009.

The company recently commenced a Phase IIa trial at Hadassah University Medical Center (Jerusalem) to assess the safety and efficacy of its oral insulin capsule on Type 1 diabetic patients. Oramed's technology is based on research conducted over 25 years at the Hadassah Medical Center.

In September, Oramed initiated pre-clinical trials of oral exenatide-4, a GLP1 analog that belongs to the incretin family of drugs that cause a reduction in blood glucose levels and inhibit glucagon secretion.

Delivery of pain medications

Akela Pharma (St. Laurent, Quebec) has completed a Phase IIb trial for its fast-acting fentanyl formulation for breakthrough cancer pain and will soon initiate a Phase III study in Europe. The drug is delivered using its Taifun multi-dose dry powder inhaler.

Taifun fentanyl is licensed to Janssen Pharmaceutica (Beerse, Belgium), a subsidiary of Johnson & Johnson (New Brunswick, New Jersey). The device combines an integrated and patented desegregation system (vortex chamber) and a humidity control system (desiccant capsule inside the drug reservoir), resulting in highly efficient fluid dynamics.

Akela uses its proprietary Lurux wet suspension formulation method to ensure powder homogeneity. The company's pipeline also includes therapeutics for asthma, COPD and growth hormone deficiencies.

Akela Pharma previously was known as LAB International and assumed its current name following its January 2007 acquisition of PharmaForm (Austin, Texas), a contract pharmaceutical manufacturing firm.

BioDelivery Sciences International (Raleigh, North Carolina) has developed two patented oral delivery systems. BEMA is a bioerodible mucoadhesive system that is designed to deliver a dose of drug across the oral mucous membranes. It consists of a small, dissolvable polymer film for application to the inner lining of the cheek. It adheres to the oral mucosa in less than 5 seconds and bioerodes in 15 to 30 minutes.

Onsolis, the company's lead product, uses the BEMA technology to deliver fentanyl for the treatment of breakthrough pain in cancer patients. In August, the FDA requested a risk evaluation mitigation strategy (REMS) for this product. FDA approval is expected in early 2009.

Meda (Solna, Sweden) will market Onsolis. A pre-IND meeting was held with the FDA for use of BEMA to deliver buprenorphine, an opiod drug for treating moderate to severe post-operative pain and for chronic pain from osteoarthritis.

Bioral is BioDelivery Sciences' patented nanocochleate technology that encapsulates a drug within a crystal matrix for oral delivery. The encapsulation provides protection from degradation caused by exposure to sunlight, oxygen, water and elevated temperatures. The company's initial product utilizing this technology is amphotericin B cochleates for the treatment of fungal infections and leishmaniasis.

Ophthalmic drug delivery

Ophthalmologists have limited drug-delivery options because eye drops are difficult to dose accurately and are naturally removed from the eye, and ocular injections and implants are highly invasive.

EyeGate Pharma (Waltham, Massachusetts) uses the EyeGate II delivery system which employs iontophoretic technology for safely and non-invasively delivering therapeutics to the anterior and posterior tissues of the eye. The system is suitable for delivery of anionic and cationic molecules.

The company's lead program is EGP-437. It is in a Phase II trial for treating severe uveitis and EyeGate plans to soon initiate a Phase II trial for the treatment of dry eye.

Retinapharma Technologies (Tampa, Florida) has licensed the PhotoTarget thermally-liable delivery system from Johns Hopkins University (Baltimore). It provides precise delivery of drugs to the retina and eliminates the need for cumbersome and risky intraocular injections to the retina and choroid for a range of photodynamic agents.

The company is using the PhotoTarget system for the delivery of liposomes in combination with an ultra-low fluence laser system for treating the wet form of age-related macular degeneration (AMD). The company has FDA approval for its TonoPach portable intraocular pressure and corneal thickness measurement device for use in diagnosing glaucoma and ocular hypertension.

Acucela (Bothell, Washington) is in a Phase I trial of ACU-4429 for treating the dry form of AMD, which encompasses roughly 90% of AMD patients and is expected to double in the next 20 years due to the increasing aging population. The drug is being co-developed with Otsuka Pharmaceutical (Tokyo).

Acucela's rebamipide ophthalmic suspension is a candidate for a Phase III trial for treating dry eye. Dry eye affects more than 10 million Americans and is one of the most common problems treated by optometrists. Rebamipide also is being co-developed with Otsuka.

Its mechanism of action is to increase the level of mucin in the conjunctiva and cornea. It is expected to be effective in dry eye treatment by stabilizing the tear film and by leading to the improvement of the corneal-conjunctival damage associated with dry eye.

(Tomorrow: A look at three more product categories from the Rodman & Renshaw conference.)