CDU Associate

In an agreement that appears to bolster the growing trend toward medical device/biotechnology combination products, device giant Medtronic (Minneapolis, Minnesota) and Genzyme (Cambridge, Massachusetts), a large biotech company that focuses on rare genetic diseases as well as other disorders, have formed a joint venture to accelerate the development of new treatments for some of the most intractable forms of cardiovascular disease.

The new venture, which is to be named MG Biotherapeutics, will combine Medtronic's skill in creating devices that deliver targeted therapies and Genzyme's research in seeking biological approaches to treating disease, initially developing products for cardiac repair and the treatment of heart disease. The new operation will employ about 50 people in three locations.

According to Scott Papillon, senior public relations manager for Medtronic, the collaboration reflects an increasing interest by his company in developing therapies that combine drugs and medical devices. "We feel that is where the industry is heading," he told Cardiovascular Device Update, "this convergence of the two, biotech and med-tech, and even information technology as well."

Papillon noted that the two companies have been in discussions for close to five years. He added that Genzyme "has been seeking to partner for some time with a company that has strong skills like we have in delivery [platforms], and we've been seeking solutions for many of the disease markets that we are in, so it was a natural marriage."

A key component to this new j-v platform, according to Papillon, was Medtronic's acquisition last September of TransVascular (Palo Alto, California), developer of the FDA-approved CrossPoint TransAccess Catheter System, which is indicated to facilitate the positioning and placement of catheters within the peripheral vasculature. The system, approved in the U.S. in 2002, has the ability to deliver therapeutic agents including cells, genes and drugs to precise locations within the vascular architecture.

While specific financial terms were not disclosed, the companies said they would share 50-50 both the research costs and the profit if a treatment is successfully developed. The companies expect to enter a late-stage clinical trial in early 2008.

The first goal of the new venture is the continuation of clinical trials on use of cell therapy to repair damaged heart tissue. Genzyme is conducting its Myoblast Autologous Graft in Ischemic Cardiomyopathy (MAGIC) Phase II clinical trials in Europe, and the company has been studying whether skeletal muscle cells can help repair damaged heart tissue. These cells, called myoblasts, are harvested from a patient who is about to undergo heart bypass surgery. The cells are cultivated in a laboratory, and then injected back into a damaged portion of the patient's heart during surgery.

This clinical trial is using myoblasts, because heart cells involved in growing new heart tissue called cardiomyocytes have little ability to regenerate in adults, the companies said. Researchers want to know if this therapy can reverse heart damage or at least halt further damage to the heart muscle.

As this Phase II trial continues, the companies will work on a way of delivering the myoblasts to the heart using Medtronic technology. They also will collaborate on next-generation cell therapies and delivery.

Stephen Oesterle, MD, Medtronic's senior vice president of medicine and technology, said in a statement that the joint venture combines Medtronic with the "remarkable talents" of Genzyme's scientific staff and its expertise in biological engineering into what he termed a "formidable venture focused on 'combination' products."

The Phase II clinical trial, which is currently being conducted in Europe with partial funding from Assistance Publique-Hopitaux de Paris, will enroll up to 300 patients. This trial builds upon the work of Genzyme's European principal investigator, Philippe Menasche, MD, PhD, of Hopital Bichat (Paris), who was among the first to test whether autologous cell therapy could be used to stop or reverse the damage done to the heart muscle by a heart attack. The trial has enrolled patients in France and is currently expanding to sites in Belgium, the UK, Italy, Germany and Switzerland.

Because cardiomyocytes have limited regenerative ability in adults, the heart has minimal potential to heal itself after a heart attack occurs. Investigators in the Phase II trial harvest a patient's myoblast cells prior to bypass surgery through a small biopsy in the leg. These cells are multiplied many-fold in the laboratory over roughly 21 days using patented cell-culture techniques. The investigators then inject the cells into a damaged region of the heart during a coronary artery bypass operation. Investigators are examining the safety of this procedure, and are monitoring a range of outcomes designed to provide a meaningful indication of potential efficacy.

While the Phase II trial progresses, the companies will work to develop a catheter-based system to deliver cells to the heart using Medtronic's TransAccess system. This device has shown potential in pre-clinical studies to effectively deliver autologous cells to damaged areas of the heart.

Medtronic and Genzyme said they believe that catheter-based delivery could make cell therapy treatments less invasive, enabling access to the heart through a patient's vascular system. They also believe that this may greatly increase the number of patients who could benefit from cardiac cell therapy.

In addition to these efforts, the companies said they will pursue a longer-range joint research program focused on potential next-generation cell therapy approaches, including the use of genetically modified cells, allogeneic cells (cells from a donor or cell bank), and advanced biomaterials designed to enhance cellular engraftment and survival.

Medtronic noted that it already has a long and successful history of combining chemical compounds or biologics with medical devices to achieve improved therapeutic results. Some notable examples are steroid-eluting leads for pacemakers and defibrillators, bioactive coatings for heart valves and heparin-coated components used in open-heart surgery. More recent examples include an investigative drug-coated coronary stent, drug infusion systems and Infuse Bone Graft, a morphogenic protein used in conjunction with spinal instrumentation. Infuse was approved in May by the FDA for the treatment of acute, open fractures of the tibial shaft.

Dan Quinn, a spokesman for Genzyme, noted that most of the company's revenues are currently derived from products that are for rare genetic diseases, and cell therapy is a promising area that the company has expanded into at a research level over the past few years.

Genzyme, which already markets a cell therapy product called Carticel that helps repair damaged cartilage tissue in the knee and Epicel, a cell therapy for treating patients with severe burns, sees this new transaction as part of an ongoing effort to expand into markets with large commercial potential, and this vascular application would be the biggest one for the company to date.

"It's certainly a larger patient population," Quinn told CDU, noting that the company had been seeking a partner to develop catheter-based delivery systems, as part of its long-term development plan for cell therapy products.

Quinn also noted that Genzyme is expanding into the large field of oncology with its planned $1 billion buy of ILEX Oncology (San Antonio, Texas), a company that develops drugs for the treatment of cancer. That deal was first disclosed in late February.

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