BB&T Contributing Writer

SAN DIEGO — Interest in device/drug combinations has grown with the enormous commercial success of drug eluting stents from Johnson & Johnson (New Brunswick, New Jersey) and Boston Scientific (Natick, Massachusetts), and the Infuse bone graft that contains recombinant human bone morphogenetic protein (rhBMP-2) from Med-tronic (Minneapolis), which has annual sales of $600 million and is projected to become a $1 billion product by 2009.

Among the many differences in developing combination device/drug products is the length of their approval processes, estimated at three to five years for devices and eight to 10 years for drugs, and their commercial viability after patent expiration with a sharp decline occurring in drug sales, but not with devices.

These were just some of the issues explained, debated and generally mulled over at the Drug-Device Summit in San Diego. The conference — sponsored by Biotechnology Industry Organization (Washington), the Advanced Medical Technology Association (also Washington), BIOCOM (San Diego) and Windhover Information (Norwalk, Connecticut), featured predominantly early development-stage companies that were seeking capital and/or corporate partners

Undifferentiated devices sought

At a Plenary Session on combination products at the Drug/Device Summit, Tom Bailey, CFO of Angiotech Pharmaceuticals (Vancouver, British Columbia), explained that his company seeks undifferentiated devices for addition of a biological agent to add value and enhance performance. As one example, he cited biopsy needles, whereby the coating of a chemotherapeutic agent could be used to treat any stray cancerous cells that may be left behind in the track created by the needle upon its removal.

Jonathan Rigby, VP of business development at Zogenix (Hayward, California), reviewed his company’s Intraject needleless subcutaneous disposable drug delivery device, being developed for use in treating migraine headaches and other CNS disorders. Zogenix’s business model differs from other companies that have had only limited success marketing their needle-less injection devices because its product is prefilled with drug and is disposable.

Paul Buckley, senior director of licensing at Wyeth (Collegeville, Pennsylvania), acknowledged significant challenges — many of a regulatory nature — when a drug company co-develops a product with a medical device company, as was the case with Wyeth’s rhBMP-2 and the bone matrix from Medtronic that are employed in the Infuse bone graft. Current efforts are focused on the use of BMPs for soft tissue repair, such as cartilage, for instance.

Proprietary coatings and biomaterials

Affinergy (Research Triangle Park, North Carolina), a spinoff from Duke University (Durham, North Carolina), is developing site-specific biological systems using biofriendly linkers that selectively adhere to proteins, drugs, cells and biomaterial surfaces. Its biologic coatings can be used to control the interface between therapeutics and surfaces and to deliver drugs and cells to surfaces as diverse as metals, polymers, tissues and biomaterials.

The company is focused on the application of its technology to medical devices. It has development and licensing agreements for use in orthopedic spine and trauma devices with Synthes (Oberdorf, Switzerland), and in bone allografts with Musculoskeletal Transplant Foundation (Edison, New Jersey). It also has research agreements with Boston Scientific for use in coronary stents, and with DuPont (Wilmington, Delaware) in an undisclosed product area.

PolyMedix (Philadelphia) is developing biomimetics for acute diseases. It focuses on novel small molecules, oligomers and polymers as non-peptide protein mimetics. They have the activity of peptides, but are easy to produce and have drug-like properties. PolyMedix’s computational platform has a wide range of capabilities, from in silico de novo drug design, to generating proprietary crystal structures of membrane-bound protein receptors, for rapidly accelerating drug discovery. The company’s preclinical programs include: development of antibiotic drugs (defensin mimetics) for ophthalmic, intravenous and topical use for the treatment of MRSA and VRE, and other resistant bacterial infections; self-sterilizing bactericidal polymers for use as coatings on plastics and textiles; and an anticoagulant antidote for heparin and low molecular weight heparin.

Topical formulations and transdermal patches

Trans-Pharma (San Diego) is a new company that seeks to develop applications of its patented Transdel site-specific topical delivery system. Initial efforts are for developing Ketotransdel, a topical NSAID formulation that combines its Transdel delivery system with ketoprofen. The Transdel cream formulation has a very low plasma concentration of the drug which avoids potential gastrointestinal, cardiovascular and renal complications. The product was shown to be efficacious and safe in a Phase I/II clinical trial using Ketotransdel as a topical treatment for soft tissue pain and soreness. There are no topical NSAIDs approved in the U.S.

Nuvo Research (Mississauga, Ontario) has developed Pennsaid, a topical NSAID formulation (diclofenac in dimethyl sulfoxide) that is licensed for sale in Canada by Paladin Labs (Montreal) for the treatment of osteoarthritis. Nuvo resubmitted its NDA to the FDA in July 2006 in its ongoing effort to gain market clearance in the U.S.

Iomai (Gaithersburg, Maryland) uses transcutaneous immunization technology developed at Walter Reed Army Hospital (Washington) to protect the skin from pathogens by targeting specialized Langerhans cells in the skin. These cells link the outer layers of skin with the lymphatic system and can carry immune-stimulating antigens and adjuvants from a patch on the surface of the skin directly to the immune system. Patients receiving the vaccines and immunostimulant patches are less likely to suffer systemic side effects.

The company is in a Phase II trial with its immunostimulant patch for treating traveler’s diarrhea and in a Phase I trial of a flu vaccine patch.

Altea Therapeutics (Tucker, Georgia) is developing its patented PassPort patch system for sustained transdermal delivery of water-soluble drugs, proteins and peptides. The PassPort system is comprised of a single-use disposable patch and a reusable handheld applicator. It can deliver up to 2 mg of protein and 10 mg of peptide and has shown to be bioequivalent to subcutaneous injection. Phase 1 clinical trials have been completed for a 12-hour insulin delivery patch for patients with Type 1 and Type 2 diabetes and for a Fentanyl citrate patch to treat moderate/severe pain.

Preclinical programs are underway using the PassPort system for treating schizophrenia and as a preventive for deep vein thrombosis. In January 2006, Altea Therapeutics signed an exclusive licensing agreement with Japan’s Teikoku Seiyaku for developing and marketing a transdermal patch containing apomorphine for the treatment of advanced Parkinson’s disease. It is in a Phase 1 clinical trial.

Novel biomaterials for drug delivery

Lux Biosciences (Jersey City, New Jersey) is using polyacrylate technology in its development of ophthalmic drug delivery systems. Polyarylates are a family of bioerodible polymers made from the amino acid tyrosine and diacids, such as glutaric acid or adipic acid. The polymer matrix allows for hydrogen bonding and other stabilizing interactions with the drug molecule and is suited for use with peptides. On exposure to body fluids, the polymer breaks down to naturally occurring metabolites. It biodegrades in about one year, which is longer than can be achieved using PLGA polymers.

Polyarylates were developed in the laboratories of professor Joachim Kohn at Rutgers University (New Brunswick, New Jersey). This polymer is used as a coating on the Pivit hernia mesh marketed by TyRx Pharma (Monmouth Junction, New Jersey). Lux Biosciences’ LX211 is a next generation calcineurin inhibitor licensed from Isotechnika (Edmonton, Alberta) for ophthalmic applications. It will be developed in an oral formulation for the treatment of uveitis. Other products to be developed are LX212 for dry eye syndrome and LX213 for aged-related macular degeneration.

Micromuscle (Link ping, Sweden) is developing electro-active polymers for use in medical devices. The behavior of these polymers can be electrically controlled, such as their ability to swell and contract in response to low voltage. The applied potential induces an electrochemical reaction that makes the polymer switch between a deactivated state and an activated state. Swelling is caused by ions and water entering the polymer. When the voltage is removed, ions and water leave the polymer, causing it to contract.

The company is focused on products used in interventional cardiology, such as guidewires, catheters, balloons and stents, and it has a collaboration with an undisclosed U.S. medical device manufacturer. Micromuscle’s technology can be used for electrically controlled release of substances contained in the polymer. Electro-active polymer technology has been researched for almost 20 years at Link ping University and its discovery was awarded a Nobel Prize in 2000.

Devices and instruments for drug delivery

Mercator MedSystems (San Leandro, California) seeks to establish adventitial therapeutic delivery as the standard of treatment for vascular and other diseases, through the successful commercialization of a novel catheter-guided, site-specific delivery device. Its minimally invasive Adventa Micro-Infusion Catheter delivers drugs and biologics directly to the passageway wall to the adventitia. It has 510(k) clearance for vascular applications. It is similar to an angioplasty catheter and is inserted through a tiny puncture to access vessels and uses a wire-guided balloon for exact placement within a body vessel. The balloon unfurls and locks the device at its desired location, pushing a micro-needle through the vessel wall and providing delivery to the adventitia without injury.

A similar system is being developed that can be inserted into open, non-vascular passageways such as the sinus, urethra and bronchi.

Ichor Medical Systems (San Diego) has developed a patented TriGrid Delivery System (TDS) that utilizes electroporation technology for the delivery of DNA drugs for use as therapeutic cancer vaccines and for therapeutic proteins and vaccines to treat infectious diseases. TDS is a handheld device that uses electrical fields to increase DNA drug delivery by up to 1,000 fold over conventional injection. The TDS electrode array for intramuscular delivery consists of four penetrating electrodes arranged in two equilateral triangles to form a diamond shape around an integrated central injection needle. The multiple and simultaneously active electrodes enhance electrical field uniformity at the site of application, thereby improving efficiency and minimizing the risk of focal tissue damage.

Ichor is about to initiate a Phase I trial on a melanoma vaccine to be conducted at the Memorial Sloan Kettering Cancer Center (New York). Ichor seeks to out-license its TDS device to companies with proprietary genes and DNA compounds.

NeoVista (Fremont, California) has developed an intraocular epiretinal radiation device for the treatment of the wet form of age-related macular degeneration. The technology consists of an intraocular probe that delivers and directs ionizing radiation to the choroidal neovascular lesion developing beneath the retina. The localized delivery of radiation permits selective treatment of the neovascular lesion while minimizing neosensory degeneration from secondary radiation exposure.

The company said it planned to present one-year data from its feasibility trial at the Royal Hawaiian Eye Meeting in mid-January. It has completed enrollment in a trial utilizing an anti-VEGF agent concomitantly with radiation in the eye. NeoVista’s device can potentially also be used for the treatment of diabetic retinopathy. The product includes a reusable radiation device, a disposable procedure pack and a multi-channel tester for source verification.

Drug/biosensing combo

MicroCHIPS (Bedford, Massachusetts) is developing drug delivery and biosensing devices for the diagnosis and treatment of various diseases. Key components of the company’s technology include proprietary reservoir arrays, hermetic sealing techniques and wireless communication technologies. Any combination of drugs or biosensors can be stored in the sealed reservoirs.

Preprogrammed microprocessors, wireless telemetry or sensor feedback loops actively control the opening of the reservoir to initiate drug release or expose the enclosed biosensor. MicroCHIPS’s technology provides improved clinical oversight and management in the fields of diabetes, cardiology, orthopedics and cancer. A MicroCHIPS-implanted device containing leuprolide has been successfully demonstrated to release the drug over a six month period, as reported in the April 2006 issue of Nature Biotechnology. Boston Scientific and Medtronic have invested in MicroiCHIPS and Medtronic has a joint product development program.

Application of light for drug delivery

Vascular Reconditioning (Snoqualmie, Washington) — currently in the process of being spun off from Lightsciences (also in Snoqualmie) — uses the combination of a photoreactive drug, talaporfin sodium (LS11), and activating light generated by an endovascular LED catheter to create site-specific, singlet oxygen-mediated effects on certain pathologic and iatrogenic targets in patients. This light-activated treatment has application as an adjunctive procedure for the prevention of restenosis following intervention in the superficial femoral artery in patients with peripheral artery disease. The development of a prototype catheter for its peripheral artery disease program has been completed and a Phase 2a trial is planned.

The company is also exploring the use of light in an endovascular procedure for stabilizing vulnerable plaque in patients with coronary artery disease that are at risk of acute coronary syndrome.

Nanospectra Biosciences (Houston) is developing minimally invasive photo/thermal cancer therapies for solid tumors using its proprietary AuroShell particles, licensed from Rice University (Houston). These particles are comprised of a thin gold shell surrounding a silica core and a new class of materials designed to absorb near-infrared and other wavelengths of light. The metal shell converts absorbed light into heat. The particles can be combined with antibodies to target specific cell types or the vasculature of tumors. The optically tunable particles are delivered intravenously and activated by a laser to generate localized areas of heat sufficient to ablate nearby tumor cells without damage to healthy tissue.

The company plans to shortly file an investigational device exemption. Its initial target is for the treatment of head and neck cancer.

GeriGene Medical (Elkhart Lake, Wisconsin) is developing the Cellagen process, a cell therapy technology platform that uses a person’s cells obtained by biopsy to grow tissues in a laboratory which are injected for replacement of damaged tissue in a variety of age-related conditions. Its products are: DermaCellagen for wrinkle removal, KeloCellagen for scar revision, UroCellagen for urinary incontinence and GastroCellagen for acid reflux. The Cellagen process is claimed to be low cost and provide long-lasting results. The company has collected six-year data on DermaCellagen which will enter a Phase II trial, pending availability of funds.