To obtain an independent review of the risks and benefits of HPI, in February 1988, Lilly convened a consultant group that examined all relevant information on HPI available. These experts shared our concerns about the safety of HPI in light of the failure to demonstrate unique efficacy. Accordingly, clinical trials with HPI were suspended in February 1988. Experience with HPI demonstrates the challenge associated with the development of new drugs in general and insulin agonists in particular.

A dimer of biosynthetic human growth hormone (HGH) has been isolated and characterized. This entity, which is the predominant dimeric species in biosynthetic HGH, is chemically identical to monomeric HGH and exists in a noncovalent dimeric form which is dissociated to monomeric HGH on polyacrylamide electrophoresis gels or in aqueous solutions containing 30% acetonitrile. This substance, found in all production lots of pituitary HGH, biosynthetic HGH, and biosynthetic methionyl HGH examined, is much less biopotent than monomeric HGH and can be distinguished from monomeric HGH by a monoclonal antibody. These data demonstrate that polyacrylamide gel electrophoresis is not a valid method for measuring this dimer and that size-exclusion chromatography under aqueous conditions is required.

No abstract