Converging medical technologies, which broadly speaking bring drugs and devices together, are becoming so important that the companies involved now need their own forum for discussion and partnering. EDB Group responded by recently setting up the first-ever “BioDevice Partnering” event in Edinburgh.
Richard Moore, director of horizontal legislation, innovation, and science at Eucomed, the Europe-wide organization for medical-device companies, said medical technology is especially relevant for the chronic diseases of the aging population.
Moore listed innovative trends in the sector, including nanotechnology, regenerative medicine, theranostics, imaging, and telemedicine. “Most medical technologies involve the convergence of different branches of science and technology. That is why companies must partner.”
“Converging technologies are key to success in healthcare,” added John Padfield, Ph.D., speaking for Scottish Enterprise, which supported the meeting, since Scotland has a well-established medical technology sector. Dr. Padfield, who is also chairman of Optos (www.optos.com), said that the company’s Panoramic200 Scanning Laser Ophthalmoscope (P200) is an example of the innovation that typifies the biodevice industry.
The standard retinal exam covers only 5% of the retina so that many disorders linked to hypertension, aging, and diabetes are missed. The P200 provides a high-resolution digital image, the optomap® Retinal Exam, which captures 80% of the retina in a quarter of a second. This offers eye-care practitioners greatly enhanced diagnostic capabilities and represents an estimated $2-billion recurring market opportunity, said Dr. Padfield.
Convergence between drugs and devices has its origins in drug delivery technology but now encompasses much more, explained David Cassak, managing partner at Windhover Information. “There are multiple ways of thinking of convergence. It is a real challenge for companies, because device and pharma companies are different in terms of scale, timelines, and other matters. There is a lot of interest among device companies in partnering with pharmas, but I am not sure if it is reciprocated.”
“Convergence is clearly here, but the drug-eluting stent may have created false expectations—it is actually hard to find winning combinations of products,” stated Richard Dakers, vp business development in the medical device and diagnostics group at Johnson & Johnson (www.jnj.com).
The first drug-eluting stents were developed by big companies, but now smaller ones are getting involved and they need help, especially with the regulatory side, which is challenging even for a large organization. There are also issues with getting physicians and surgeons to adopt new medical technology, more so in Europe than in the U.S., and with reimbursement.
The FDA’s new Office of Combination Products has yet to prove itself—while a conventional device may get through, they may be too risk-averse to deal with anything more innovative. Despite the challenges, the expert panel believed biodevices (a new term, defined loosely as a product or platform where the pharma/drug and device components were both important) could be transformational, with regenerative medicine and electrical stimulation technologies thought to be particularly promising.
Trends in Biodevices
The major trends in biodevices are in the areas of orthopedics, cardiology, biomaterials, and regenerative medicine.
Organogenesis (www.organogenesis.com) is focused on regenerative medicine products, involving collagen, fibroblasts, and keratinocytes.
Apligraf, a skin replacement product for burns and wound healing, launched in 1998 and is now selling 700 units a week, according to the company.
Sales are increasing, said vp Dario Eklund, but the product is only reaching 2% of the applicable market at present, so there is still a lot of potential growth. Apligraf is bilayered—fibroblasts in a collagen matrix and a keratinocyte-containing top layer.
VCT-01™ , which is in development, is an improved form of Apligraf. It has a human rather than bovine matrix and is stronger.
TestSkin® is being used by cosmetic companies to test products. As animal testing is phased out, the market for this is likely to increase.
Intercytex (www.intercytex.com) is at various stages of clinical trials with its four cell therapy products for wound healing, scars, wrinkles, and hair regeneration. Lead product, ICX-PRO, for chronic venous ulcers and diabetic ulcers, is a clear competitor for Apligraf.
ICX-PRO and the scar and wrinkle products are based on allogeneic fibroblasts. The hair-regeneration product is based on autologous cells that are taken from the base of the hair follicle. “We want to set a new standard in ease of use and storage,” said Nick Higgins, CEO. “We are trying to make cell therapy appropriately priced, which will broaden the market.”
Cartilage and bone repair are other leading areas in regenerative medicine. Scil Technology (www.scil.com) is developing products for orthopedic and dental tissue regeneration with an emphasis on bone and cartilage repair. These products are composed of recombinant growth factors combined with biodegradable materials to stimulate the formation of new tissue.
The company has identified three growth factors; one of these, rhGDF-5, is a bone morphogenic protein that is being applied specifically to dental tissue and is the active pharmaceutical substance in lead product, MD05, a synthetic granulated bone substitute.
This product is intended for bone augmentation prior to dental implant and for treatment of severe periodontal disease, where the bone, as well as the surrounding tissue supporting the teeth has worn away and where there is no effective regenerative treatment currently available.
According to Weishui Weiser, Ph.D., managing director, it has proof-of-concept on the action of rhGDF-5 in animal models, and a Phase II trial of MD05 is currently being conducted in Germany.
The company also has ongoing projects in orthopedics. They have proof-of-concept for bone augmentation in spinal fusion procedure and for cartilage repair following both accidental damage and degeneration due to osteoarthritis.
Cartela(www.cartela.com) is working on an integrin, a type of cell-surface receptor found specifically on chondrocytes. This marker can be used to pick out cells with chondrocyte potential in mesenchymal stem cells.
TiGenix (www.tigenix.com) is focused on understanding the cell biology of stable hyaline cartilage and the pathogenesis of osteoarthritis in the hope of developing the first-ever durable repair for a worn-out or damaged knee joint. The company’s lead product, ChondroSelect™, an autologous cell therapy for cartilage repair, is in Phase III trials. This trial, at 15 centers, compares the therapy with microfracture, a standard surgical procedure for knee repair.
Adult stem cells express high levels of aldehyde dehydrogenase (ALDH). Aldagen (www.aldagen.com) has developed a substrate that makes stem cells emit a green fluorescence, based on the high expression of ALDH, and is the central component of their product Aldesort.
These cell populations are known as ALDH bright (ALDHbr) and can readily be isolated by Aldesort, according to the company. The ALDHbr cell population contains hematopoietic, mesenchymal, endothelial, and neural progenitors. The cells have the ability to revascularize, which has been shown in studies in a mouse model of hind limb ischemia. Additionally, ALDHbr cell populations are producing favorable comparisons with unfractionated bone marrow cells, with fewer ALDHbr cells being needed to produce a significantly better therapeutic effect in animal models.
“ALDHbr cells are more potent than whole bone marrow,” explained Tom Amick, chairman and CEO.
Aldagen has received FDA clearance to begin two clinical studies to the treat congestive heart failure and critical limb ischemia patients. Aldagen also has a third clinical trial under way to isolate ALDHbr cells from cord blood with the aim of decreasing platelet and neutrophil engraftment times.
Brain repair is also a hot area in regenerative medicine. ReNeuron (www.reneuron.com) is developing therapies, based on adult stem cells for stroke, Parkinson’s disease, diabetes, and diseases of the retina. The company’s c-mycERTAM technology is a stem cell expansion platform. It works by adding the c-myc gene to the cells via a retrovirus and then adding 4-hydroxytamoxifen that acts as a trigger.
“This is a highly effective technology for generating lots of cells,” said John Sinden, Ph.D., CSO. The cells produced in this way have been shown, in a rat model of stroke disability, to migrate into the damaged area.
Growing cells for therapeutic and other applications is labor intensive, for they have to be fed every day, which is challenging if the process is to be scaled up for commercial use.
To meet the need for automation NovaThera (www.novathera.com) created a bioreactor, the TheraMachine, and is a lead commercial partner in a U.K. Department of Trade and Industry-sponsored consortium on manufacturing issues in stem cell technologies.
One main aim is to decrease the amount of culture and plasticware needed, which will cut costs. NovaThera is focused on novel methods of culturing and differentiating human and mouse embryonic stem cell (ESCs). They have cultured a type II pneumocyte from human ESCs and human umbilical cord cells, which has already been applied in mouse models of lung disease.
A collaborative program with NovaLung (www.novalung.com), which makes an assisted lung device, led to the development of a miniaturized human lung containing the pneumocyte, which has great potential for preclinical testing of compounds.