News and issues that affect organ and tissue transplantation



Is the Transplant Drug Glass Half Empty or Half Full?

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There is optimism (and concern) regarding pharma's commitment to new transplant drugs

Although many transplant professionals worry that big pharma may be less committed to the development of new immunosuppressant drugs than in the past, some are optimistic, especially in light of new genetic findings and investigations of agents that target relevant cell surface molecules and intracellular pathways.

John Neylan, MD, senior vice president, Clinical Research, at Genzyme Corporation, understands the concern that fewer drugs are in development; however, he says, “I think it oversimplifies the situation. Clearly transplantation is still in evolution and I suggest that we are in one of the most exciting times in its entire history. The science has never been stronger. I think it all speaks to a very strong commitment to develop new therapeutics.”

Dr. Neylan and others agree that challenges persist, such as the very real difficulties of conducting meaningful clinical trials under the current regulatory constraints, mandating problematic comparators and study design endpoints of diminishing relevance.

Additionally, Randall Morris, MD, head of Therapeutic Sciences for Transplantation and Immunology at Novartis Pharma AG, notes that, “given the complexity, risk and costs of developing a new immunosuppressant, a significant barrier remains for companies that are first entering the field.

“The cost of necessarily complex trials and increasing emphasis on benefits versus risks by regulatory agencies are all barriers to entry,” continued Dr. Morris. “However, the quality and novelty of most of the immunosuppressants now in trials are greater than many of the drugs studied in the 1990s and first years of the 21st century. One would hope, therefore, that the attrition rate for immunosuppressants now in trials will be lower and that their potential will be greater.”

Clearly transplantation is still in evolution and I suggest that we are in one of the most exciting times in its entire history. The science has never been stronger. I think it all speaks to a very strong commitment to develop new therapeutics.—John Neylan, MD

Meanwhile, some of the former players in transplant drug develdevelopment may have changed their business focus. For example, while noting a continuing commitment to transplantation—including further studies with their product CellCept and investment in the Roche Organ Transplant Research Foundation (ROTRF)—Urs Schleuniger, vice president for Strategic Marketing, Inflammation, at Roche, says the company has decided to discontinue its investment in basic transplantation research. However, Roche “is still committed to evaluating potential new medicine for transplantation from biotech or other sources,” he notes.

Fewer Drugs in the Pipeline

As authors Flavio Vincenti, MD, and Allan Kirk, MD, point out in their comprehensive look at specific compounds in the pipeline (p. 1970), “the lack of novelty in transplant therapeutics is reflected in the trial registry”

Dr. Morris agrees, noting that there are only about half a dozen immunosuppressant drugs in substantial Phase 2 or Phase 3 transplant trials, despite the critical need for better immunosuppressants. Reasons for the decline are many and complex.”

He adds that an additional barrier “is the failure of the scientific and clinical transplant experts in academia to collaborate more closely with scientists and clinicians in industry.”

Another barrier to drug development is “technical challenges, because we don't understand all the immunology yet and some of the things we thought we understood have turned out to be more complicated biologically,” says Joe Camardo, MD, senior vice president of Global Medical Affairs at Wyeth Pharmaceuticals. “There's the technology hurdle and then there's the development hurdle. It's not an issue of commitment from the industry; there are several stumbling blocks.”

On the Verge of New Therapeutics?

Dr. Camardo says that, “I believe that science is going to come up with the answers that look pretty difficult now. You never give up hope. I believe we'll eventually get to something resembling tolerance. We thought we'd have it in the 80s, then in the 90s, and it's now the first decade of the next century. It's just taking longer than we anticipated.” Dr. Neylan says, “we're on the verge of new ways of working with many therapeutics, and in transplantation, like oncology, we may soon discover better markers of adaptive immune responses and other measures to individualize therapies depending upon genetic make-up or other phenotypic markers. These are heady days, and I would suggest that there's never been a more exciting time to be in drug development.”

Another reason for optimism, says Dr. Morris, is that, “since there is clearly a critical need for safer, more effective and less complex means to suppress rejection, the market for transplant immunosuppressants is far from saturated.” He continues, “despite the complexity of the field, we have an industry that is experienced with long-term commitment to transplantation and collaboration with academia. With these elements, we will be successful in creating therapeutics of great benefit to patients and in allowing a return on investment to support the discovery and development needed to create the next generation of transplant immunosuppressants.”