The Wire

Abstract

Clinical wire

Aastrom Biosciences IMPACT-DCM Trial

The U.S. Food and Drug Administration (FDA) has lifted its clinical hold from the phase II IMPACT-DCM clinical trial being conducted by Aastrom Biosciences, Inc. The IMPACT-DCM trial is evaluating the use of cardiac repair cells (CRCs), a mixture of stem and progenitor cells derived from a patient's own bone marrow, for the treatment of dilated cardiomyopathy (DCM), a severe form of chronic heart failure. In May 2009 the trial was suspended after a patient died after treatment. On the basis of autopsy results and medical records, the FDA and Data Safety Monitoring Board have determined that the patient's death was due to progression of the disease and not the CRC treatment. Forty patients at five different clinical sites will be enrolled in the trial. (sk)

Targeted Genetics tgAAC94 Trial in Inflammatory Arthritis Subjects

A new report has been published in the New England Journal of Medicine, presenting the case history and autopsy results from a widely publicized Targeted Genetics-sponsored phase I/II AAV2 gene therapy clinical trial of rheumatoid arthritis that resulted in the death of a 35-year-old woman in July 2007. Dr. Karen Frank and colleagues ¹ conclude in the report that the cause of death was due to a disseminated, recrudescent infection with Histoplasma capsulatum, and not the gene therapy agent. “For most of her life, this patient lived in a region in which this fungus was endemic,” the authors wrote. “Although clinical manifestations occur in less than 1% of infected persons, viable organisms can remain in a latent state, and reactivation can occur when immunity is suppressed, such as when a person is being treated with a TNF-α antagonist.” The patient received concurrent anti-TNF-α and other immunosuppressive therapy throughout the duration of the trial. According to an editorial by Dr. Elizabeth L. Hohmann ² of the Partners Human Research Committee, “there are important lessons to be learned from this case that are relevant to several constituencies with interests in clinical trials.” Most notable of which is the importance of considering endemic infections when pursuing an immunosuppressive regimen in tandem with gene therapy. (sk)

Footnotes

Industry wire

Genentech announced that it is taking a stake in Bayhill Therapeutics, a California-based biotech that is built around the BHT-DNA antigen-specific immunotherapy platform used to induce tolerance to autoreactive proteins in autoimmune disease. Specifically, Genentech will pay $25 million up-front cash and equity for rights to use the biologic BHT-3021, which is being developed by Bayhill Therapeutics for type 1 diabetes. BHT-3021, a plasmid encoding proinsulin, is currently in a phase I/II trial in which it is administered intramuscularly.

NanoCor Therapeutics , a North Carolina-based company, received a cash infusion from Medtronic to the amount of $2.5 million. NanoCor focuses on a congestive heart failure treatment using biological nanoparticles (BNPs) and self-complementary AAV vector technologies, which are derived from human recombinant adeno-associated viral (rAAV) vectors. The funds will be used to develop and commercialize its gene therapy products.

Geron Corporation , the biotechnology company based in Menlo Park, California that received the first U.S. Food and Drug Administration (FDA) approval of a human embryonic stem cell-related clinical trial, now announces that it is partnering with General Electric (GE). The venture aims to develop commercial products from embryonic stem cells for toxicity testing in drug development. According to Konstantin Fiedler, general manager of cell technologies at GE Healthcare, the goal is not to sell actual stem cells but rather the stem cell-derived differentiated cells with the goal of minimizing animal trials.

Targeted Genetics , the AAV-based gene therapy company, announced that it will cut more than half of its workforce. The company also terminated the lease on the large manufacturing space it held but never occupied. These cost-saving measures are part of a plan intended to either continue operations or enable continued development of AAV-based gene therapeutic products through another entity, according to Susan Robinson, the president and CEO of the troubled firm.

Tech wire

References

Frank

K.M.

et al. 2009. N Engl J Med, 361:161–169.

Hohmann

E.L.

2009. N Engl J Med, 361:193–195.

Gitzinger

et al. 2009. Proc Natl Acad Sci USA, 106:10638–10643.