Technology review

There have been two important hurdles to developing treatments for neurodegenerative conditions: the fact that many compounds in development are proteins - large molecules that are hard to deliver to the central nervous system - and the difficulty in getting neurons to regenerate.

Amgen Inc., which has several neurotrophic factors in development for neurodegenerative disorders, added a small molecule capability to its portfolio with the acquisition last week of rights to Guilford Pharmaceuticals Inc.'s neuroimmunophilin ligand program (see BioCentury Extra Aug. 22). AMGN could spend up to $465.5 million to expand its portfolio of neurological drugs, but with only $48.5 million guaranteed, the risk seems modest compared to the potential benefits of GLFD's compounds.

AMGN's overall pipeline is focused on three broad clinical categories: hematopoietic factors, inflammation, and neuroendocrine factors. Within the neuroendocrine branch, AMGN (Thousand Oaks, Calif.) appears to be almost exclusively concentrating on neurodegenerative diseases and conditions. The exception for AMGN is leptin, which has a neuroendocrine role in obesity, and has completed Phase I testing.

AMGN's core neurology program (excluding leptin) now consists of three protein neurotrophic growth factors and GLFD's neuroimmunophilin ligands, which are in preclinical development. The early-stage nature of AMGN's neurology pipeline raises the question of whether the company will forego development of some of its proteins if GLFD's small molecules prove to be superior.

AMGN acquired glial-derived neurotrophic factor (GDNF) in 1994 when it purchased Synergen Inc. for $240 million, and is developing the protein for Parkinson's disease and amyotrophic lateral sclerosis (ALS). Phase I data for GDNF in about 100 Parkinson's patients are expected in mid-1998.

AMGN's other two protein growth factors - brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) - are being developed with partner Regeneron Pharmaceuticals Inc. (REGN, Tarrytown, N.Y.). In a Phase III study, BDNF failed to show clinical efficacy in 1,100 ALS patients (see BioCentury Jan. 13).

The lure

Neurotrophic protein growth factors have given academic scientists enormous clues about the normal development of neurons and other tissues, and those findings created optimism over the last several years that the proteins could be used for medical applications.