Introduction
The treatment of hemophilia A and B has improved considerably in recent years. The
availability of hepatitis A and B vaccines, safer clotting factor concentrates (particularly
recombinant factor VIII and recombinant factor IX concentrates), and synthetic agents,
such as desmopressin,1 has resulted in earlier, more aggressive treatment and prophylactic regimens aimed
at preventing chronic, debilitating joint disease.2-8There have been no new cases of human immunodeficiency virus (HIV) disease attributable
to clotting factor in North America since 1987, and documented instances of hepatitis
transmission by clotting factor concentrates have been rare in the 1990s. Concerns
remain that certain nonenveloped viruses, such as human parvovirus B19 and hepatitis
A virus, can still be transmitted by some plasma-derived clotting factor concentrates,9and questions linger as to whether the agents causing Creutzfeld-Jacob disease (CJD)
and new variant CJD might also be transmitted. Overall, however, the products available
to treat hemophilia today are safer than ever before.
An increasing number of persons with hemophilia are receiving exclusively recombinant
(r) products, and manufacturers are now producing new, second-generation r-factor
VIII products that are stabilized with sugars, rather than albumin, or are smaller,
truncated molecules.10 Scientists are now designing specific changes into the factor VIII genes in an attempt
to derive unique and improved forms of r-factor VIII.11 The next logical areas of focus are to bring to fruition the promise of an “unlimited
supply” of r-factor VIII and r-factor IX products, to meet the needs of persons with
hemophilia, not only in developed countries, but throughout the world, and to be able
to cure hemophilia through gene therapy.
As gene therapy trials begin in humans with hemophilia, the scientists involved, the
United States Food and Drug Administration (FDA), and perhaps most importantly, members
of the hemophilia community must decide which categories of affected individuals should
be entered in these trials, particularly the earliest, Phase I trials. Who is most
likely to benefit if gene therapy proves to be both effective and safe? Who should
be the first patients to be enrolled in each new trial? Who is at greatest risk if
something unexpected happens? What would be considered a good outcome? Clearly, some
of these questions are more difficult to answer than others.
