BBI Contributing Editor

NEW YORK – A total of 302 public and private companies made presentations at the annual Techvest healthcare conference sponsored by Rodman & Renshaw (New York). The large majority of these companies were pharmaceutical and biotechnology firms with offerings in all the major disease categories. This report covers many of the companies that featured proprietary drug delivery technologies by the oral, transdermal, mucosal and pulmonary routes, as well as several of the biomaterials and medical equipment companies.

Depomed (Menlo Park, California) uses its patented gastric retention technology for the oral delivery of its own products and for collaboration with pharmaceutical and biotechnology companies. This technology is de-signed for drugs that are absorbed in the upper intestinal tract and can keep drugs in the stomach for up to 12 hours. Drugs that utilize the gastric retention technology are glumetza, an extended release form of metformin for Type 2 diabetes that is marketed by Biovail (Mississauga, Ontario, Canada) and proquin, an extended release form of the anti-infective ciprofloxacin that received FDA approval earlier this year. Depomed has collaborations with Boehringer Ingelheim (Ingelheim, Germany) and New River Pharmaceuticals (Radford, Virginia) on undisclosed drugs. The company is in clinical trials with gabapentin, a generic version of Pfizer’s (New York) Neurontin.

Vyteris Holdings (Fair Lawn, New Jersey) has developed the LidoSite Topical System for dermal anesthesia. It is used to reduce the pain of venipuncture and IV cannulation in patients aged five and older. The single-use, pre-filled LidoSite patch contains lidocaine and epinephrine. It is used in conjunction with a controller that allows for precise dosing. This iontophoretic system is branded the Actyve transdermal drug delivery technology. It delivers drugs through the skin using low-level electrical energy and has precise control over the rate and amount of drug infused, thereby duplicating the performance of an IV infusion pump. The LidoSite system was recently introduced in the U.S. by Vyteris’ marketing partner, B.Braun Medical (Bethlehem, Pennsylvania), a subsidiary of B. Braun (Melsungen, Germany). The company’s development pipeline includes products for the treatment of female infertility, migraine and Parkinson’s disease.

Unigene (Fairfield, New Jersey) is a developer of oral and nasal delivery systems for peptide drugs used to treat osteoporosis. It has developed the Fortical (recombinant calcitonin-salmon) nasal spray, which is claimed to be the first drug approved in the U.S. for the treatment of postmenopausal osteoporosis. It was launched in August 2005 by Upsher-Smith (Maple Grove, Minnesota). Also under development for treating osteoporosis are Unigene’s oral calcitonin which is in a Phase I/II trial and oral parathyroid hormone which is in a Phase I trial and is licensed to GlaxoSmithKline (London).

The company recently announced its acquisition of exclusive rights to inventions that it had jointly owned with Yale University (New Haven, Connecticut) for new methodologies to treat and prevent fractures. One invention is for accelerating bone growth in precisely targeted locations using a simple surgical procedure that can be performed with minimal intervention on an outpatient basis in combination with one or more therapeutic compounds. Another invention covers unique devices that could be used to facilitate bone repair or to create novel prostheses.

Products for hormonal and sexual disorders

Vivus (Mountain View, California) develops proprietary products to restore sexual function for men and women. It markets the MUSE transurethral delivery system for alprostadil for treating erectile dysfunction. The company licensed from Acrux (Melbourne, Australia) a metered dose transdermal spray (MDTS) that is being used in a Phase II study to deliver testosterone for the treatment of low libido in premenopausal women, and in a Phase III 400-patient study of Evamist (estradiol MDTS) for the treatment of vasomotor symptoms associated with menopause. Vivus also is conducting a Phase IIB clinical trial of Alista, a topically applied patented formulation of alprostadil, for the treatment of female sexual arousal disorder.

Columbia Laboratories (Livingston, New Jersey) is developing a series of vaginal gel products that contain a patented bioadhesive delivery system comprised of the mucoadhesive polymer, polycarbophil, and an active ingredient. It markets Prochieve 8% progesterone gel as part of an assisted reproductive technology treatment for infertile women. This product also is in a Phase III trial for use in the prevention of pre-term birth.

Prochieve 4% progesterone gel is being marketed for the treatment of secondary amenorrhea and is under evaluation by a third party for the treatment of endometrial hyperplasia. A Phase II trial was recently initiated on a lidocaine vaginal gel for the prevention and treatment of dysmenorrheal and pelvic pain. The company is in discussion with outside partners on the development of a testosterone vaginal gel or tablet for fibroid reduction and sexual dysfunction and for a desmopressin buccal tablet for treating nocturnal enuresis.

Antares Pharma (Exton, Pennsylvania) has assembled several proprietary drug delivery technologies. It markets the Medi-Jector Vision reusable needle-free injection device in more than 30 countries to deliver insulin or human growth hormone. The company is developing the Vibex disposable mini-needle injection device and is exploring the possibility of having its own drug/device combination products using this device. Its ATD (advanced transdermal delivery) system containing ibuprofen is being sold in several foreign countries for treating pain. An ATD gel containing oxybutynin is in a Phase II trial for use as a treatment for an overactive bladder.

Antares Pharma has licensed to BioSante Pharmaceuticals (Lincolnshire, Illinois) LibiGel, an ATD transdermal gel containing testosterone that is in a Phase II clinical trial for treating female sexual dysfunction. BioE-Gel, an ATD gel containing estradiol and norethindrone has completed a pivotal Phase III clinical trial for treating women with menopausal symptoms such as hot flashes. It is licensed to both BioSante Pharmaceuticals and Solvay Pharmaceuticals (Brussels, Belgium). Antares Pharma’s Easy Tec fast-melt oral-disintegrating tablets are designed for use by patients, such as the elderly, that have difficulty swallowing pills, tablets or capsules.

BioSante Pharmaceuticals also is developing Bio-T-Gel, a once-daily transdermal gel containing testosterone for the treatment of hypogonadism in men. Bio-E/P Gel (estradiol + progestogen) is being developed as a once-daily transdermal gel for treating menopausal women. The progestogen serves to reduce the risk of endometrial hyperplasia. BioSante has also developed what it believes to be formulations for the oral delivery of proteins. Pre-clinical trials of oral insulin are under way.

Inhalation therapy systems

There is increasing interest today in medication delivered through the lungs, which provides faster delivery than oral pills because, as with an injection, it bypasses the digestive tract.

Aradigm (Hayward, California) has developed two drug delivery systems. Intraject is a needle-free, single-use pen-sized system that delivers liquid drug formulations to the subcutaneous layers of the skin. A pilot pharmacokinetic study using the Intraject device to deliver sumatriptan for treating migraines yielded positive results. Aradigm is seeking a commercial partner for this product.

The company’s AERx breath-activated device is for the pulmonary delivery of liquid drugs. The drug is converted into a fine-particle mist that is released only when the patient inhales correctly. Its most advanced program is a collaboration with Novo Nordisk (Bagsvaerd, Denmark) using the AERx device for delivering insulin to diabetic patients.

Aradigm recently reported a development agreement with United Therapeutics (Silver Spring, Maryland) for use of the AERx system to deliver a liposomal formulation of treprostinil as a treatment for pulmonary arterial hypertension. The company also entered into an agreement with an undisclosed global pharmaceutical company in the area of smoking cessation using its inhalation system for delivering nicotine into the bloodstream via the deep lung.

LAB International (Laval, Quebec) is focused on the inhalation market using its patented TAIFUN dry powder inhaler, a multi-dose, reservoir-based system that consistently delivers a uniform dose into the deep lungs. Its lead product is a fast-acting fentanyl formulation in Phase II clinical trials for the treatment of breakthrough cancer pain. The TAIFUN inhaler has been approved in 10 European countries for the delivery of the asthma drug salbutamol.

LAB International is in a small Phase I trial using inhaled calcitonin gene related peptide for treating asthma. It also is conducting a Phase II trial on an inhaled 29-amino acid peptide analogue of growth hormone releasing hormone for the treatment of wasting in patients with late pre-dialysis chronic renal failure. In addition, the company’s development pipeline includes therapeutics for chronic obstructive pulmonary disorder (COPD) and other growth hormone deficiencies. LAB International also operates a contract research organization.

Mannkind (Valencia, California) is in Phase III clinical trials in the U.S. and Europe for its inhaled Technosphere insulin system that is being used to treat patients with Type 1 and Type 2 diabetes. The therapy consists of a dry powder Technosphere formulation of insulin that is inhaled into the deep lung using the company’s proprietary MedTone inhaler, which provides a rapid transfer of insulin into the blood. The company also is investigating the use of its inhaler for the pulmonary delivery of drugs to treat metabolic and immunological diseases.

Inyx (New York) has niche drug delivery technologies that are used for treating respiratory, allergy, dermatological and cardiovascular conditions. It is one of only several companies with expertise in non-ozone depleting aerosol pharmaceuticals which is mandated by many countries including the U.S. More than 90% of the asthma inhalers sold in the U.S. last year contained ozone-depleting chlorofluorocarbon (CFC) propellants that will need to be converted into non-CFC inhalers.

Inyx has proprietary technology in hydrocarbon aerosol foam pharmaceuticals that can be used to replace conventional dermatological creams and liquids. The company’s platform of inhalation drug delivery products includes dry powder inhalers, metered dose inhalers, metered dose nasal sprays and oral sprays. Inyx also has a patented technology that utilizes a lipid-binding matrix for delivering incompatible or unstable drugs. In September, Inyx reported a collaboration with King Pharmaceuticals (Bristol, Tennessee) to develop new formulations using hydroalkane, a non-ozone depleting propellant, for two of King’s inhaled anti-inflammatory agents.

Novel biomaterials

Bacterin International (Belgrade, Montana) is a private biomaterials company that is developing anti-infective coatings that it licenses for medical applications. The bioactive coatings are based on knowledge of the physiological changes made by microbes as they sense and adapt to changes in their environment. The company recently began clinical trials of OsteoSponge, a bone filler used for spinal fusion and dental applications.

Bacterin has a development contract with Baxter (Deerfield, Illinois) to coat peripheral vascular access devices. It also is developing an antimicrobial coating for orthopedic medical devices for the U.S. Department of Defense (Washington) and has additional projects for applying its technology to surgical wound drains and for developing natural scaffold matrices used in regenerative medicine applications. Its coatings are claimed to provide controlled release of therapeutic agents with the duration of release ranging from hours to several months.

Protein Polymer Technologies (San Diego) uses protein-based biomaterials to develop products for use in soft tissue augmentation, tissue adhesives and sealants, wound healing support and drug delivery devices. It is developing for Spine Wave (Shelton Connecticut) an injectable disc nucleus for the repair of damaged spinal discs for treating lower back pain.

The company is in pilot clinical trials with a urethral bulking agent for female stress urinary incontinence and an implant for correction of dermal contour deficiencies. Pre-clinical studies are underway on a surgical sealant that is designed to prevent air and fluid leaks following lung, gastrointestinal and cardiovascular surgery.

In July, Protein Polymer Technologies reported its intention to acquire Surgica (El Dorado Hills, California), a company that develops and markets embolization products and has three FDA-approved polyvinyl alcohol foam embolization particles.

Medical equipment

Curon Medical (Fremont, California) is a developer and marketer of products that use radiofrequency (RF) energy for treating disorders of the gastrointestinal tract. The company reported strong sales growth for its Secca system, which delivers RF energy into the muscle of the anal sphincter for the treatment of bowel incontinence. Its Stretta system is used to perform a minimally invasive outpatient endoscopic procedure for the treatment of gastroesophageal reflux disease (GERD). The Stretta system consists of a flexible and disposable catheter and the Curon Control Module. It is used by a physician to deliver temperature-controlled RF energy that creates thermal lesions in the muscle of the lower esophageal sphincter and the gastric cardia (uppermost portion of the stomach), thereby improving GERD.

Somanetics (Troy, Michigan) markets the INVOS (in vivo optical spectroscopy) cerebral oximeter, the only commercially available monitoring system that continuously and non-invasively monitors changes in a patient’s regional brain blood oxygen saturation. This device is used in situations where there is a high risk of brain oxygen imbalances, such as cardiac surgeries and other major surgeries involving elderly patients.

Somanetics reported that it had just received 510(k) clearance from the FDA to market INVOS technology to monitor changes in blood oxygen saturations in regions of the body other than the brain. A new application could be as an adjunct trend monitor of hemoglobin oxygen saturation of blood in skeletal muscle tissue beneath the sensor in infants, children and adults at risk of reduced flow or no flow ischemic states in critical care settings.

The company also markets the CorRestore system, an implant used in cardiac repair and reconstruction including during surgery for ventricular restoration, a procedure that is performed on patients with certain types of severe congestive heart failure

Medicsight (London) develops computer-aided detection (CAD) software that is used as an aid in the early detection of diseases. Its software solutions help clinicians identify, measure and analyze suspicious pathology, such as colorectal polyps and lung lesions. It has received clearance from the FDA for ColonCAD, the first high-performance medical imaging software tool designed to assist radiologists in searching for potential colorectal neoplasia (polyps) with CT colonography (virtual colonoscopy), and for LungCAD, used to evaluate pulmonary nodules on CT scans of the lung and chest. These systems are in the process of being launched in the U.S. They already are sold in Europe and China.

Medicsight recently reported non-exclusive agreements with Viatronix (Stony Brook, New York) for incorporating its ColonCAD and LungCAD into Viatronix’ V3D medical imaging workstations, and with TeraRecon (San Mateo, California) to allow users of its Aquarius medical imaging products to add the ColonCAD and LungCAD image analysis software tools.