Endocrine Abstracts

The growth hormone receptor antagonist was discovered via expression of mutated GH genes in transgenic mice. Although we were attempting to generate potent GH analogs, our mouse studies indicated that the compound was ‘inhibiting’ GH action. We subsequently showed that it was a GH receptor antagonist, the first of its type. Many hurdles needed to be ‘jumped’ in the development of this compound into a drug including protection of intellectual property; funding for purification, preclinical, and clinical trials; and registration to and approval by the various regulatory agencies. Ultimately the compound was approved in the mid-2000s for the treatment of patients with acromegaly. The name of the drug is Somavert (Pegvisomant for injection). Pegvisomant treatment in a dose dependent manner results in normalization of IGF-1 levels in most patients and has been found to be safe and efficacious. Since the GH/IGF-1 axis has been implicated in the progression of several types of cancers, many have suggested the use of Pegvisomant as an anti-cancer therapeutic. In this talk, I will describe experiments in which the GHA was discovered, review results of Pegvisomant’s preclinical and clinical trials, and provide data suggesting Pegvisomant’s value in selected types of cancer.

Key Learning Points: • Unexpected experimental findings can, at times, be very promising.

• Trials and tribulations of translating laboratory finding to the patient.

• Serendipity played an important role in our drug development process.