10 october 2010 1737© The American Society of Gene & Cell Therapy doi:10.1038/mt.2010.204 editorial Would-be gene and cell therapists have longed for the day when they could escape the
Trang 1Molecular Therapy vol 18 no 10 october 2010 1737
© The American Society of Gene & Cell Therapy
doi:10.1038/mt.2010.204
editorial
Would-be gene and cell therapists have
longed for the day when they could escape the sneer that their field was 5 years from success—and has been that way for 20 years Fortunately, our wish has been granted, for
an increasing number of reports of clinical success
in genetic diseases and cancer are appearing in high-profile journals and are being widely ac-knowledged But now that this first stage has passed, we are left with what is in many ways a more intractable problem How do we ensure that safe and effective complex biological therapies (CBTs) become licensed products that are suf-ficiently viable from a commercial standpoint to
be widely distributed as the standard of clinical practice? In a series of articles over the coming
year, Molecular Therapy will examine these issues
in more detail, but I will begin by outlining the problem here
Some gene and cell therapy approaches—for example, the use of plasmid or virus injection
or unmodified banked cells—may be relatively simple to develop, implement, and disseminate;
most, however, will not be Instead, they are true complex biologics that are almost impossible to fit into the standard model of drug development
on which modern medicine has come to largely rely Unlike small-molecule or even protein thera-peutics, CBTs are often individualized, may need multiple iterative early-phase clinical studies to optimize each component, have extensive embed-ded intellectual property, and are expensive to manufacture and distribute Moreover, CBTs are intended to be curative rather than ameliorative, and so a single treatment may substitute for the conventional chronic administration required for small molecules and proteins Of course, many of these same problems apply to preexisting complex biologics such as organ transplants, and in partic-ular to allogeneic hemopoietic stem cell transplan-tation (HSCT), that have long been established
as standards of clinical practice Unfortunately,
introduction of their modern equivalents has become much more difficult and complex, owing
to profound changes in the regulatory and medi-cal-economic climate If HSCT protocols were be-ing introduced now, they would be shut down on toxicity concerns long before their benefits could become apparent
Although the above concerns have discouraged commercial interest in developing CBTs, several factors are beginning to change this appraisal With the rise in the power of genomic/proteomic/ metabolomic analyses of diseased tissues and host responses, it is becoming feasible to design and develop more personalized therapeutics targeted
to the specific disease state of an individual As
a consequence, pharmaceutical companies are coming to appreciate that their standard model of drug development and marketing will no long ap-ply even to new “standard” drugs, giving them a strong incentive to develop creative approaches to individualized drug development Implementing these new approaches will require dialogue with drug regulatory agencies to establish new criteria for registration that increase access to effective agents while minimizing any increase in risk Once agreed on, these criteria could almost certainly be extended to CBTs Second, the development in the United States and Europe of an increasingly centralized payer system will favor introduction
of therapies that have the optimal pharmaco-economic profile—with fewest side effects, highest quality of life, and greatest persistence of benefit Comparative effectiveness/health-services analyses
of CBTs will almost certainly favor many of them over conventional agents and should lead to diver-sion of centralized funding to their support In the United States, this shift will probably be aided by the National Institutes of Health, which is already supporting or considering supporting registration trials for CBTs, albeit on a more limited scale than could be achieved either by industry or by the US Department of Health and Human Services as a
Clinical Success of Complex Biological Therapies:
Be Careful What You Wish For
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© The American Society of Gene & Cell Therapy
editorial
whole Finally, success breeds optimism, and the recent
approv-al of the Provenge vaccine for prostate cancer has undoubtedly
provided a fillip to industrial interest, although successful
com-mercialization of this approved CBT may be a challenge
In Europe, CBTs are called “advanced therapy med icinal
products,” or ATM-Ps Unfortunately, this is a misleading
acronym because, unlike the more familiar type of ATM, an
ATM-P can currently only consume rather than dispense
mon-ey Our desire for the next 5 years is that we will reverse this
tendency, and in subsequent issues of Molecular Therapy we
will discuss how this wish may be fulfilled
Malcolm K Brenner
Editor-in-Chief