BB&T Contributing Writer

NEW YORK – The 9th annual healthcare conference sponsored by Acumen BioFin, the life science financing arm of Rodman & Renshaw, featured 369 presenting life science and specialty pharmaceutical companies, with six companies presenting simultaneously, representing a veritable who's who in the industry. The list of companies included many private and international firms. Rodman & Renshaw touted its leadership position in terms of more than $2.6 billion raised for companies in this sector during the period from 2003 to Sept. 2007.

The use of proprietary drug delivery technologies figured prominently in the presentations of the emerging pharmaceutical companies. A proliferation of technologies are being used to extend the effective lifetime of a drug and reduce its side effects.

Oral and buccal drug delivery

Durect (Cupertino, California) is developing drugs that utilize its proprietary drug delivery platform technologies. Two of these drugs are in Phase III trials. They are Remoxy which uses its Oradur gel-cap for the oral delivery of long acting oxycodone for the treatment of chronic pain that is licensed to King Pharmaceuticals (Bristol, Tennessee) and Pain Therapeutics (San Mateo, California); and Memryte, which uses its Durin biodegradable implant to deliver leuprolide acetate for the treatment of Alzheimer's disease and is licensed to Voyager Pharmaceuticals (Raleigh, North Carolina). Two drugs that are in Phase II trials and utilize Durect's Transdur transdermal patch technology are sufentanil for relief of chronic pain for up to seven days that is licensed to Endo Pharmaceuticals (Chadds Ford, Pennsylvania) and bupivacaine for post-herpetic neuralgia. Durect has licensed from EpiCept (Tarrytown, New York) intellectual property for a transdermal patch containing bupivacaine for the treatment of back pain.

Penwest Pharmaceuticals (Danbury, Connecticut) develops drugs based on its proprietary oral drug delivery technologies such as its TIMERx platform technology that is adaptable to soluble and insoluble drugs and can provide a variety of drug release profiles. It is used in the company's lead drug, Opana ER (oxymorphone HCl), a twice daily opiod for treating moderate to severe pain and which is marketed by Endo Pharmaceutical (Chadds Ford, Pennsylvania). Additional oral delivery systems are Geminex, a dual drug delivery system for independent release of combined active agents, and SyncroDose, a drug delivery system which releases the drug at the desired site and time in the body. Penwest is transitioning from being a drug delivery company that provides improved oral formulations to becoming a drug development company focused on niche neurological compounds.

Generex Biotechnology (Toronto) is pursuing drugs for delivery through the oral mucosa, with no deposit in the lungs. Its leading product is Oral-lyn, an oral insulin spray for the treatment of Type I and Type 2 diabetes that uses the company's proprietary RapidMist applicator. It is sold in Ecuador and is in late stage clinical trials around the world. Generex has partnered with Cardinal Health (Dublin, Ohio) for the manufacture of Oral-lyn. Generex markets in North America the Glucose RapidSpray for use at the first feeling of low blood sugar, between meals and during exercise. It is in a Phase II trial on metformin gum, a proprietary chewing gum that provides absorption through the buccal mucosa and avoids the side effects associated with oral metformin. Fentanyl and morphine sprays for the treatment of breakthrough pain are in Phase I trials.

BioDelivery Sciences International (Raleigh, North Carolina) uses its BEMA (BioErodible Muco-Adesive) disc technology for delivering drugs to treat pain and for infections. The disc adheres to the oral mucosa within 5 seconds. The company recently submitted an NDA for BEMA Fentanyl for treating breakthrough cancer pain. It is licensed in Europe to Meda AB (Solna, Sweden) and a U.S. licensing partner is being sought. BEMA Buprenorphine is completing a Phase I trial for patients with moderate to severe pain. It is a long-acting narcotic analgesic that is less addictive than morphine or oxycodone. The company plans to enter a clinical trial in 2008 for Bioral amphotericin B, an orally available anti-fungicide.

Drug/polymer delivery systems

Pro-Pharmaceuticals (Newtown, Massachusetts) uses combinations of carbohydrates with existing chemotherapeutic agents to provide longer lasting efficacy with reduced toxicity and side effects. Its lead product, Davanat, is in a Phase II trial for the treatment of colorectal cancer. It uses a combination of 5-fluorouracil with a polysaccharide that has a mannose backbone and galactose side chain, a variety of which is found in nature. The polysaccharide targets galectins on cancer cells. The company is conducting preclinical work on combinations with other cancer drugs including doxorubicin, paclitaxel, oxaplatin and cisplatin.

Access Pharmaceuticals (Dallas) is developing ProLindac, a polymer-linked platinum cancer drug, oxaliplatin, that is in a Phase II trial in Europe in ovarian cancer patients. It uses the principles of nanoparticle prodrugs to enhance the delivery of a platinum drug to tumors. ProLindac was shown in preclinical trials to protect normal tissue from the cytotoxic effect of platinum while in circulation and to increase the tumor's drug uptake. The platinum is released by virtue of a pH-sensitive linker. The company has FDA clearance to market MuGard for treating oral mucosistis. It is applied to the ulcer as a liquid and forms a protective filmic barrier. The product is licensed in Europe to Spe Pharm (Amsterdam, the Netherlands) and a licensing partner is being sought in the U.S.

Enhanced vaccine Delivery

Iomai (Gaithersburg, Maryland) uses transcutaneous immunization technology to deliver vaccines and immune system stimulants. An enhanced immune response is generated by tapping into the Langerhans cells in the outer skin layers which enhances the efficacy of vaccines The company recently reported favorable results from its needle-free patch-based diarrhea vaccine for travelers. The company plans to begin a Phase III trial in 2008. An immunostimulant patch used in conjunction with vaccines for pandemic influenza is in a Phase I/II trial. The patch is designed to induce robust immune responses with low doses of vaccine, for what is expected to be a limited supply of vaccine during a pandemic. This program is funded by the Department of Health and Human Services (Washington).

Inovio Biomedical (San Diego) is using its electroporation-mediated DNA delivery technology for developing vaccines for cancer and infectious diseases. This technology can increase gene expression one hundredfold compared to naked DNA, resulting in heightened levels of humeral and cellular responses. Phase I/II trials are underway on vaccines for treating melanoma that is licensed by Vical (San Diego) and for treating prostate cancer. Enrollment has been completed for a Phase I trial of the MedPulser DNA delivery system for potential use against breast, colorectal, ovarian and lung cancers that is licensed by Merck (Whitehouse Station, New Jersey). Inovio is collaborating with the National Cancer Institute (Bethesda, Maryland) and with the International AIDS Vaccine Initiative (New York) on an HIV DNA vaccine. Wyeth (Madison, New Jersey) has licensed Inovio's delivery technology on an HIV DNA vaccine and has compiled positive preclinical data on non-human primates.

Itranasal delivery of peptides and proteins

Nastech Pharmaceutical (Bothell, Washington) is a leading developer in the field of intranasal delivery of peptides and proteins. It is in Phase II trials on exenatide nasal spray for treating Type II diabetes that is licensed to Amylin Pharmaceutical (San Diego) and PYY3-36 nasal spray for treating obesity by inducing satiety. The company recently announced that Procter & Gamble (Cincinnati) has pulled out of its collaboration with Nastech on a Phase II study of nasally delivered parathyroid hormone (PTH1-34) for treating osteoporosis. Par Pharmaceutical (Woodcliff Lake, New Jersey) distributes Nastech's generic salmon calcitonin nasal spray. Novo Nordisk (Copenhagen) has programs with Nastech for the nasal delivery of drugs for multiple undisclosed indications. A new area of research at Nastech is the development of therapeutics that utilize RNA interference (RNAi) technology.

Topically applied creams and gels

MacroChem (Wellesley Hills, Massachusetts) is using its SEPA drug delivery technology for the topical application of drugs. The company's lead product, EcoNail, is a SEPA-based econazole lacquer for the treatment of nail fungus, known as onychomycosis. Opterone, a SEPA-based cream containing testosterone, is being developed for treating hypogonadal males. It differs from marketed testosterone topicals in that it contains half the dose of testosterone in half the volume and is a cream, rather than a gel. It showed efficacy in raising circulating testosterone levels in a randomized, 3-way crossover, single-dose study in which it was applied to the upper arms and shoulders. The company is seeking a partner prior to undertaking a Phase II trial. In an effort to broaden its portfolio, MacroChem acquired from Genaera (Plymouth Meeting, Pennsylvania) in July the worldwide rights to pexiganan, a small peptide anti-infective to treat mild diabetic foot infections. Previously conducted studies include two Phase III trials. An NDA was submitted to the FDA in 1998, but the FDA requested an additional controlled study.

Nexmed (East Windsor, New Jersey) employs its NexAct skin permeation technology to produce nontoxic topically applied drug formulations. The company recently filed an NDA with the FDA and with Health Canada for Alprox-TD, a cream containing alprostadil for treating erectile dysfunction. Its pipeline of topically applied drug formulations includes NM100060, a lacquer for treating nail fungus and Femprox, a cream containing alprostadil for treating female sexual dysfunction for which a Phase II study was completed in the U.S. The company subsequently conducted a 400-patient placebo-controlled study in China on Femrox and is seeking a U.S. co-development partner with which to pursue a U.S. Phase III trial. Nexmed has an exclusive worldwide partnership with Novartis (Basel) for a topical anti-fungal drug.

Columbia Laboratories (Livingston, New Jersey) employs its patented bioadhesive drug delivery technology in a range of hormonal drugs, including the progesterone supplementation products Crinone gel for infertile women with progesterone deficiency, Prochieve gel for secondary amenorrhea, and the Striant testosterone buccal system for treating hypogonadism in men.

Under development are a vaginal lidocaine product to prevent and treat dysmenorrhea in a Phase II study and Prochieve vaginal gel in a Phase II study to reduce the risk of preterm birth in women with a short cervix in mid-pregnancy. Its bioadhesive delivery system consists of the polycarbophil polymer and an active ingredient. The polymer adheres to the epithelial surfaces or mucosa and is discharged upon normal cell turnover which occurs every 12 to 72 hours.

Columbia Laboratories has licensed its Replens vaginal moisturizer and RePhresh vaginal gel to Lil' Drug Store (Cedar Rapids, Iowa). Ardana Bioscience (Edinburgh) is sponsoring a trial using Columbia's testosterone vaginal gel for treating infertility. It is also the European marketing partner for Striant.

Transdel Pharmaceuticals (La Jolla, California) conducted a placebo-controlled clinical trial of Ketotransdel, a topical cream-based NSAID for treating acute pain and soreness. The products is a transdermal formulation of the NSAID, ketoprofen, using the company's proprietary Transdel drug delivery system. Transdermal delivery may minimize systemic exposure and have reduced side effects. The company is seeking a marketing partner for Ketotransdel.

Antares Pharma (Ewing, New Jersey) uses its EasyTec technology platform for producing tablets with excipients that enhance the rate of oral disintegration. The company recently announced a worldwide licensing agreement with an undisclosed pharmaceutical and consumer products company for using the EasyTec fast-dissolving technology to develop an opiod analgesic for transmucosal delivery. Key therapeutic areas for EasyTec tablets are pain management, allergies, anti-emetics and appetite suppression.

Antares Pharma's ATD transdermal gels have potential use in genitourinary, CNS, women's health and hormone replacement applications. Its Elastin gel, a fast-drying formulation of estradiol, is used to treat moderate to severe hot flashes. It was developed in collaboration via BioSante Pharmaceuticals (Lincolnshire, Illinois) and is marketed by Bradley Pharmaceuticals (Fairfield, New Jersey). Its Anturol oxybutynin gel is in a pivotal 600-patient trial for the treatment of an overactive bladder.

Drug-producing implant

Medgenics (Karmiel, Israel) is developing the Biopump which can be described as "disruptive technology" for the delivery of therapeutic proteins. This novel biological pump is created by excising a very small segment of dermal tissue which is harvested from under a patient's skin. The dermal tissue is processed ex vivo and transduced with a viral vector having non-immunogenic properties that carries the appropriate gene into the nuclei of the tissue's cells that causes the cells to produce the selected protein, thereby converting the dermal tissue into a sustained action Biopump.

The Biopump produces and delivers the protein steadily for six months or more. When it is no longer needed, the Biopump can be inactivated using ablation. The company is developing Epodure for producing and delivering erythropoietin for which the proof-of-principle was shown in a clinical trial on anemic patients, and Infradure for producing interferon-alpha to treat hepatitis C.

Needleless injection devices

Bioject Medical Technologies (Portland, Oregon), a leader in needle-free injection devices for liquid medications, markets the Biojector 2000, a handheld, reusable jet injector for general use. Its drug reconstitution system allows for the transfer of diluents to reconstitute powdered medications into liquid forms and withdrawal of liquid medication into a syringe without the use of a needle. Vitajet 3 is a portable spring powered jet injector with a disposable syringe for insulin delivery.

Devices under development for delivery of vaccines and other therapeutics are Iject, a small disposable personal injector, and Vitavax, a single-use, auto-disable spring-powered system. Bioject developed the Cool-Click and Serojet two-component, portable, spring powered jet injector for Merck Serono, a division of Merck KGaA (Darmstadt, Germany), for use in delivering growth hormones.

Sustained delivery of ophthalmic drugs

InSite Vision (Alameda, California) develops ophthalmic drugs having sustained delivery. Its AzaSite (azithromycin) ocular antibiotic for the topical treatment of bacterial conjunctivitis was recently introduced in the U.S. by Inspire Pharmaceuticals (Durham, North Carolina).

It uses InSite's patented DuraSite sustained delivery technology which comprises a synthetic polymer-based formulation that is designed to extend the residence time of a drug. The company has completed a Phase I trial on AzaSite Plus, a combination of azithromycin and dexamethasone, an anti-inflammatory drug for treating bacterial infection and inflammation.

Microspheres as Contrast Agents

Acusphere (Watertown, Massachusetts) is focused on creating porous microspheres that are smaller than red blood cells and can pass through the smallest blood vessels to deliver drugs intravenously. The company recently completed clinical trials on its lead product, Imagify (perflubutane polymer microspheres) injectable suspension. It is an ultrasound contrast agent that enables stress echocardiography to assess myocardial perfusion for the early detection of coronary artery disease.

Phase I trials are underway on a reformulated paclitaxel for cancer therapy and a reformulated asthma drug.