The race for dominance in the development of anti-tumornecrosis factor to treat septic shock has become a big-companycontest, and its outcome is anybody's guess.
The field was considerably simplified by this week'sannouncement that Bayer AG has licensed Celltech Group plc'shumanized anti-TNF monoclonal antibody in a $47.8 milliondeal. The agreement solidifies Bayer's position as the dominantplayer in anti-TNF monoclonal antibodies and avoids a possiblepatent dispute between Celltech and Bayer/Chiron Corp. Bayeralready holds rights to Chiron's first-generation anti-TNFmouse MAb.
But at least three other companies are working on TNF-relatedproducts for shock, and the data are not yet in on whichapproach will be superior.
There is room for several TNF-based products, as long as theyavoid patent disputes, said analyst David Webber of Alex.Brown & Sons. Inc. He estimates the U.S. sepsis market at600,000 cases per year, with an annual growth rate of 10percent.
Among the competing TNF-based approaches, furthestadvanced in the clinic is Centocor Inc.'s CenTNF chimericantibody. European Phase III trials will begin in July, with amarketing application anticipated for 1993, said James Woody,senior vice president and director of R&D.
Centocor (NASDAQ:CNTO) has said it would delay CenTNF'sdevelopment if necessary while it does further trials of itsCentoxin MAb, which is directed against gram-negativebacterial endotoxin. That has prompted some analysts tospeculate that the drug doesn't work as well as the companyhoped and that its patent position is weak.
"Since anti-TNF is at least as viable as an anti-endotoxinstrategy at this point, one wonders why Centocor would bepicking Centoxin," said Cowen & Co. analyst David Stone. "Thedirection the market is going is for a broad factor like IL-1 orTNF. We believe that Centocor's relatively weak patent positionon CenTNF may be a factor in their willingness to delay CenTNFin favor of Centoxin."
"There have been more than a few hints from Centocor thatCenTNF has problems, although they haven't been specific,"said Webber.
"In our clinical studies, we've found TNF is more complex thanour animal models predicted," said Centocor's Woody. "It'sharder to tell exactly what's going on with the patients andmore difficult to evaluate efficacy than with other antibodies."
In earlier development is Immunex Corp.'s soluble TNFreceptor. The Seattle company (NASDAQ:IMNX) plans to beginPhase I trials in early summer, said spokeswoman ValoreeDowell.
"The interesting point about this is that Immunex is uniquelyable to compare soluble IL-1 receptor and soluble TNFreceptor, and they've chosen the latter," said Stone. "They thinkthe TNF receptor is better for sepsis."
Genentech Inc. in December reported in the Proceedings of theNational Academy of Sciences that its TNFR-IgG preventeddeath in a mouse model of septic shock. The drug links theouter portion of the human cell receptor for TNF to part of theImmunoglobulin G antibody.
That drug is being developed by Roche, which owns 60 percentof the South San Francisco, Calif., company (NYSE:GNE).
Webber figures that the sepsis market will be split during thenext four to five years, with anti-endotoxin products holdingabout 15 percent to 25 percent of the market and cytokineinhibitors holding the rest.
He's splitting the cytokine segment evenly between TNF andinterleukin-1 inhibitors until one establishes clear superiority.Filings for marketing approval of the Bayer/Chiron monoclonaland for Antril IL-1ra by Synergen Inc. (NASDAQ:SYGN) areboth likely in the first half of 1993, "so the question will behow they stack up against each other," Webber said.
"My intuitive feeling is that IL-1 inhibition will turn out to bethe better approach because even if TNF is a more importantmediator in the septic cascade, as a medical strategy it may belimited by the short visibility of TNF as a target forintervention," Webber said.
-- Karen Bernstein BioWorld Staff
(c) 1997 American Health Consultants. All rights reserved.