BBI Contributing Editor

NEW YORK – The 6th annual Healthcare Conference hosted by Rodman & Renshaw (New York) featured 240 companies, including 30 privately held firms, operating in the fields of drug-delivery technologies, medical devices, specialty pharmaceuticals, vaccines and gene therapy. The conference, formerly known as Techvest, brought together emerging growth biotechnology and medical technology companies, institutional investors and venture capitalists.

A review of companies that presented proprietary drug-delivery technologies, diagnostic and therapeutic medical equipment and devices follows.

Drug-delivery systems

NovaDel Pharma (Flemington, New Jersey) is developing formulations of currently approved drugs for administration as lingual sprays. The benefits of this approach are claimed to be faster onset of action by absorption through mucosal membranes, a lower dose which could mean reduced side effects and greater convenience for better patient compliance, especially among the pediatric and geriatric populations which may have difficulty swallowing pills or capsules. Six drug formulations are being developed using proprietary lingual spray technology. NovaDel intends to partner with pharmaceutical and biotechnology companies for development and commercialization of drugs for administration by lingual spray. Its lead product is a nitroglycerin spray for angina licensed to Par Pharmaceutical (Spring Valley, New York), for which a new drug application was filed with the FDA in June. The other lingual spray drugs in pilot pharmacokinetic studies include alprazolam (anxiolytic), propofol (anesthetic), sumatriptan (migraine headache), ondansetron (anti-nauseant) and zolpidem (hypnotic).

Sontra Medical (Franklin, Massachusetts) has developed the SonoPrep ultrasound-mediated skin permeation device for fast, painless and safe drug delivery. The ultrasonic energy disorganizes the lipid bilayer of the stratum corneum and creates microchannels in the skin through which fluids and analytes can be extracted and large molecules delivered. The company received FDA clearance in August for the SonoPrep device used with topical lidocaine for rapid skin anesthesia, reducing the onset of numbness from 60 to five seconds. The company recently announced promising initial clinical trial results of a 20-patient study that evaluated the immune response induced by using the company's SonoPrep skin permeation device to facilitate transdermal delivery of antigenic proteins, tetanus and candida albicans (yeast). Products under development at Sontra include a continuous non-invasive glucose monitor developed in collaboration with Bayer Diagnostics (Leverkusen, Germany) and the use of SonoPrep for the transdermal delivery of vaccines and large-molecule drugs.

DUSA Pharmaceuticals (Wilmington, Massachusetts) seeks to broaden the application of its photodynamic therapy (PDT) for light-activating drugs in the field of dermatology. The company currently markets Levulan (aminolevulinic acid) and PDT for the treatment of pre-cancerous actinic keratoses. Phase II multicenter clinical trials for use of Levulan and PDT for the treatment of moderate to severe acne vulgaris of the face and for the treatment of photodamaged skin are under way. In the latter study, three different light sources are being used. In addition to DUSA's BLU-U blue light, intense pulsed light from Lumenis (Yokneam, Israel) and a long pulsed dye laser from Cynosure (Chelmsford, Massachusetts) are used. A Phase II trial also was initiated earlier this year for use of Levulan and PDT for treating high-grade dysplasia in Barrett's esophagus.

Durect (Cupertino, California) reviewed its pipeline of drugs that incorporate novel delivery technologies and include several products for pain relief. A Phase II clinical trial was recently initiated for its post-operative pain depot using its patented SABER delivery system. It is a sustained-release formulation of bupivacaine that is administered, via injection, around an incision site following surgery for up to 72 hours of regional pain relief. A Phase I trial in Europe of its transdermal sufentanil patch was also just announced. The trial is a pharmacokinetic study in healthy volunteers. The patch is intended to provide relief of chronic pain for up to seven days, as compared to the three days of relief provided by Duragesic from Johnson & Johnson (New Brunswick, New Jersey), a transdermal fentanyl patch that recorded sales over $1.6 billion in 2003. Sufentanil also is the active ingredient in Durect's Chronogesic implant for patients with opioid responsive chronic pain that is being partnered with Endo Pharmaceuticals (Chadds Ford, Pennsylvania) for the U.S. and Canada. This clinical program is currently on hold. Durect is collaborating with Pain Therapeutics (South San Francisco, California) in the development of Remoxy, a long-acting oral formulation of oxycodone that uses the Oradur oral gel-cap technology.

MacroChem (Lexington, Massachusetts) is developing drug formulations that utilize SEPA, its patented absorption enhancer. The company is conducting a Phase I study of EcoNail, a topical lacquer treatment for onychomycosis, a fungal nail infection. In August, MacroChem announced top-line results of a pharmacokinetics study of Opterone, a topical cream for male testosterone deficiency which showed that testosterone is delivered into the bloodstream within the first few hours. It had a more sustained delivery over 24 hours than the prior gel formulation. The cream vanishes rapidly after being rubbed on. The Endocrine Society estimates that only 200,000 of the nation's 4-5 million hypogonadal men are currently being treated. The company's much-touted Topiglan topical cream for erectile dysfunction failed to meet primary clinical endpoints in a Phase II pharmacodynamic study that compared efficacy to a placebo cream.

Cytomedix (Rockville, Maryland) featured its AutoloGel system which produces, under the direction of a physician, an autologous platelet gel composed of multiple growth factors and fibrin matrix for the treatment of chronic, non-healing wounds. AutoloGel is prepared by harvesting a patient's platelet-rich plasma and mixing it with ingredients that stimulate activation of the fibrinogen and platelets and also causes the liquid to become a gel. Clinical trials are underway for use of this system to treat diabetic foot ulcers.

INyX (New York) has proprietary aerosol drug delivery technologies for private label as well as internal use with prescription and over-the-counter pharmaceuticals. The non-ozone depleting hydrofluoroalkane is used as the gas propellant. The company also has expertise in hydrocarbon aerosol foams, which can be used to replace cream and lotion formulations in dermatological and topical applications. INyX recently acquired a patented platform technology that uses a lipid-binding matrix for delivering incompatible or unstable drugs. It will be used to improve the delivery of inhalation therapy drugs and overcome aerosol delivery incompatibility for combination drugs. Research and development and production are conducted at its subsidiary, INyX Pharma Ltd. (Manchester, UK). INyX's initial products are expected to be introduced next year.

LAB International (Laval, Quebec) produces drugs for use in inhalation therapy to treat respiratory diseases as well as for pulmonary delivery for systemically active drugs. Its LABhaler is a disposable single-dose dry powder inhaler and Taifun is a multi-dose powder inhaler. The company operates two business units. LAB Pharma develops novel therapeutics and LAB Research provides contract research services to the pharmaceutical and biotechnology industries. Its lead product, a formulation of fentanyl for treating breakthrough cancer pain, uses the company's Taifun dry powder inhaler technology and is expected to enter a Phase IIa clinical trial before year-end. LAB International expects to launch the bronchodilator, salbutamol, in a Taifun dry powder inhaler, in Europe in 2005. The company's pipeline also includes growth hormone releasing hormone for growth hormone deficiencies and calcitonine gene-related peptide for asthma.

Aradigm (Hayward, California) is developing systems for the delivery of drugs through the lungs and skin surface. Its AERx pulmonary drug inhalation device utilizes the lung's ability to rapidly absorb and transfer drugs and the proof-of-concept has been shown in more than 50 human clinical trials for multi-sized molecules. The AERx delivery system electronically guides the patient through the inhalation process, converts the drug into a highly-reproducible fine particle mist and releases the drug only when the patient inhales correctly. Novo Nordisk (Bagsvaerd, Denmark) is in Phase III clinical trials with the AERx insulin diabetes management system and has assumed all development and manufacturing responsibilities for this product with Aradigm to receive royalties on future sales. Aradigm recently acquired the Intraject technology, which uses a disposable needle-free system to deliver liquid drug formulations into the subcutaneous tissue. A pre-filled volume of a drug is contained in a glass capsule and nitrogen gas is used to power the drug through the skin surface. Aradigm recently reported that the IntraJect device has met its initial primary endpoint of injection performance in clinical verification trials.

Bioject Medical Technologies (Bedminster, New Jersey) is a major supplier of needle-free drug delivery systems for injectable medications. Its lead product, Biojector 2000, is a gas-powered device used for subcutaneous and intramuscular injections. VitaJet is a spring-powered injector used for subcutaneous self-injection in the home. The SeroJet and Cool.click spring-powered injectors were developed for Serono (Geneva, Switzerland) for delivery of growth hormones for AIDS wasting and recombinant human growth hormone for pediatrics, respectively. Iject, a gas-powered, disposable and lightweight needle-free device, is being developed for delivery of injected drugs and vaccines. The Iject-R is a gas-powered, reusable device that is capable of multiple injections with pre-filled disposable syringes. It is being developed for home use. Bioject has a collaboration agreement with PATH to develop a needle-free, single dose cartridge immunization system. PATH is an international nonprofit organization whose mission is to improve the health of people by advancing technologies and encouraging healthy behaviors.

Diagnostic, therapeutic equipment

EP MedSystems (West Berlin, New Jersey) manufactures a line of cardiac electrophysiology products used for diagnosing, monitoring and visualizing arrhythmias. These abnormalities in the heart's rhythm are caused by disturbances in the electrical activation of the heart muscle that causes the heart to pump less efficiently. They result in more than 1.2 million hospitalizations and 400,000 deaths each year in the U.S. and account for about 20% of all chronic heart conditions. Earlier this year, EP MedSystems launched three new products. Its ViewMate intracardiac ultrasound catheter imaging system consists of a ViewMate ultrasound imaging console and Viewflex intracardiac imaging catheters for high-resolution, real-time ultrasound capability and improved visualization of the inside of the heart chambers. The EP-WorkMate electrophysiology workstation integrated with the RPM real-time position management navigation technology from. Boston Scientific (Natick, Massachusetts) is approved by the European Notified Body for sale in 15 European countries. The ALERT system is used to treat atrial fibrillation. It uses a patented electrode catheter to deliver measured, variable, low energy, biphasic electrical impulses directly to the inside of the heart to convert atrial fibrillation to a normal heart rhythm.

International Medical Innovations (IMI; Toronto) is developing non-invasive and minimally invasive tests for the detection and monitoring of cardiovascular disease and the detection of early-stage cancer. Its Prevu Point of Care coronary artery disease predictor is a three-minute professional test that is approved for sale in the U.S., Canada and Europe. The test provides a quantifiable color-change reaction that indicates the amount of cholesterol in the skin. It is licensed to McNeil Consumer Healthcare, a subsidiary of Johnson & Johnson, and will soon be launched in the U.S. and Canada. The Prevu Home test has a consumer format for use in the home. It yields a semi-quantitative measure of cholesterol and is not yet approved for sale. IMI is conducting clinical trials of Colorect Alert, a minimally invasive screening test for the detection of colorectal cancer that is claimed to have five times fewer false positive results than existing tests for colorectal cancer. LungAlert, a non-invasive screening test, is in clinical trials for lung cancer. A breast cancer test performed on nipple aspirate has been shown in initial studies to detect early stage disease. IMI has 20 clinical trials in progress in Canada, the U.S. and internationally.

Grant Life Sciences (Research Triangle Park, North Carolina) is a newly formed company that is developing patented protein-based diagnostic products that measure antibodies for cervical cancer and cervical cancer precursors. Its AbReact analyte-specific reagents Elisa test will be sold as an adjunct to existing technologies. It is based on detecting antibodies to E2, E6 and E7 that are found in women with cervical cancer but not in healthy patients. The QuickStrip physician's office test is being developed for sale outside the U.S., especially in undeveloped countries. A single drop of blood is used and results obtained in 12 minutes. The products are claimed to possess higher sensitivity and greater reliability than currently available tests. Results from preliminary experiments have shown 97% sensitivity and 85% specificity.

Celsion (Columbia, Maryland) is developing cancer treatments using focused-heat energy. Its Prolieve Thermodilution System for the treatment of benign prostatic hyperplasia (BPH) was recently launched by its marketing partner, Boston Scientific. Celsion is conducting a Phase I prostate cancer dose escalation study using ThermoDox, lisposome-encapsulated doxorubicin, in combination with Prolieve which provides heat to trigger drug release. This heat-activated liposome technology was licensed from Duke University (Durham, North Carolina). A Phase I trial was recently initiated, in collaboration with the National Institutes of Health (Bethesda, Maryland), for the use of ThermoDox and radiofrequency ablation for the treatment of liver cancer. The use of ThermoDox and heat for the treatment of breast cancer is also being investigated. Two heat sources – adaptive phased array focused microwave technology licensed from Massachusetts Institute of Technology (Cambridge, Massachusetts) and advanced phased array radiofrequency system licensed from Duke – are under consideration. The heat-activated liposomes offer the advantages of making the tumor vasculature more "leaky," rapid drug accumulation in the tumor, and reduced side effects due to targeted delivery.

RITA Medical Systems (Mountain View, California), which recently merged with Horizon Medical Products (Manchester, Georgia), manufactures oncology devices. These include radio frequency ablation (RFA) systems for treating tumors and percutaneous vascular and spinal access products (VAP) used to deliver drugs to patients undergoing infusion therapy. The RFA system consists of a radiofrequency generator and disposable electrosurgical devices that deliver controlled thermal energy to the targeted tissue. It has FDA clearance to treat liver cancer and metastatic bone cancer.

The VAP line of products include implantable ports, safety infusion sets, high-flow tunneled central venous catheters, and peripherally inserted central catheters used in cancer treatment protocols. The company's proprietary Vortex technology is incorporated in its line of vascular access ports and has been clinically shown to reduce complications and interventions resulting from the build up of residues in the port chamber. RITA Medical Systems' products are sold to over 2,000 hospitals and cancer centers in the U.S., Europe and Asia.

MicroMed Technology (Houston) is a private, venture capital-funded company that has developed a miniaturized heart pump or ventricular assist device, known as the MicroMed DeBakey VAD. The National Aeronautics and Space Administration (Washington) and Drs. Michael DeBakey and George Noon were instrumental in the development of this axial flow heart pump. Compared to currently marketed VADs, the DeBakey VAD is about one-10th the size and one-eighth the weight (4 ounces vs. 2 pounds). It is capable of pumping in excess of 10 liters per minute.

According to the American Heart Association (Dallas), only 2,000 to 2,200 donor hearts are available each year and more than 4,000 patients are listed to receive a transplant. The number of patients that can use a mechanical support device is estimated at between 50,000 and 100,000.

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