Research from Thomas Jefferson University scientists suggests theobese (ob) gene, which Amgen Inc. licensed for $20 million last year,may yield an effective treatment for only a small percentage ofclinically overweight people.

Robert Considine, of Thomas Jefferson University, in Philadelphia,told BioWorld Today the study conducted by him and his colleaguesrevealed obese people have much more leptin, the protein from theob gene, than lean people.

The findings, published in this week's New England Journal ofMedicine (NEJM), counter previous research indicating that adeficiency of the leptin hormone _ which signals the brain to stopeating and to increase metabolic rates _ may be a major contributingfactor in obesity.

The NEJM study, which measured leptin levels in the blood of 275obese and lean people, was an expansion of data Considine and hisfellow researchers published last year in the Journal of ClinicalInvestigation. (See BioWorld Today, June 6, 1995, p. 1.)

"The obese people had four times more leptin than the lean people,"Considine said. "But about 5 percent to 10 percent of the obesepeople had leptin levels lower than the average."

For the subgroup of overweight people with lower leptin levels,Considine said, injections of leptin may be an effective treatment tohelp blast the "stop eating" signal. The principle is similar to therapyfor Type II diabetes sufferers, who produce insulin but are givenmore of the hormone to get their bodies to respond to its message forcontrolling glucose levels.

The vast majority of obese people in the Thomas Jefferson study,Considine observed, have suitable amounts of leptin. "They'reinsensitive to leptin," he said, "and it is less likely that leptin therapywould benefit them."

Obese News Had Little Affect On Stock

Although the NEJM report suggests Amgen's leptin may not be assignificant as first thought in the battle against obesity, Amgen'sstock (NASDAQ:AMGN) was unaffected by the news.

Shares rose $2.87 to $63 Thursday on the strength of Amgen's year-end earnings report, which showed a 23 percent jump in net incomefor 1995. The increase was fueled by $1.8 billion in sales of its twomarketed products, Epogen and Neupogen.

David Kaye, spokesman for Amgen, said the NEJM study was notsurprising. "Obese people have higher levels of leptin in their bloodthan lean people because leptin is manufactured in fat cells," he said."We did the same experiments and found the same things."

It has not been proved, Kaye added, that obese people are resistant tothe leptin hormone's signal.

The ob gene and its leptin expression created considerableexcitement last year when it was revealed that obese mice, which hada defective ob gene, lost weight dramatically after receivinginjections of leptin. (See BioWorld Today, July 27, 1995, p. 1.)

The scientists studying the leptin concluded the hormone was anappetite suppressant, which not only told the brain to stop eating, butalso to increase activity to burn off calories.

Amgen, of Thousand Oaks, Calif., licensed the ob gene in March1995 from New York-based Rockefeller University where it wasdiscovered and expects to begin clinical trials by the end of this yearusing leptin as a weight-reducing treatment.

Considine said the Thomas Jefferson University research suggeststhat another significant target for battling obesity may be the leptinreceptor, which apparently is not responding to the "stop eating"signal carried by the hormone.

Millennium Pharmaceuticals Inc., of Cambridge, Mass., and itscorporate partner, Roche Holdings Ltd., of Basel, Switzerland, areworking on the receptor approach. In December 1995, theirresearchers identified and cloned the leptin receptor in the brain. (SeeBioWorld Today, Dec. 29, 1995, p. 1.)

More Than One Potential Treatment

Because obesity is a polygenic disease, Considine said, it isunrealistic to think that an effective treatment for all overweightpeople could come out of one gene.

The research, he added, allows scientists for the first time to identifydifferent groups of obese people.

"All we have had up to now is a scale that says you're obese," heobserved.

Considine said he and his Thomas Jefferson University colleagueswill continue measuring leptin levels in people, but they also areworking with the receptor.

Amgen, in addition to paying a $20 million licensing fee for the obgene, agreed to make milestone payments to Rockefeller Universitytotaling as much as $70 million.

However with more than $1 billion in cash and annual revenuesapproaching $2 billion, the company's investment in the ob gene wasnot considered significant. In 1995, Amgen spent $451 million onresearch and development, a 40 percent increase over the $323million in 1994.

Amgen's 23 percent jump in net income to $538 million was $102million more than the $436 million profit the previous year. Per shareearnings for 1995 were $1.92 compared with $1.56 for 1994. The1994 earnings' figures do not include a $116 million charge relatedto Amgen's buyout of Synergen Inc., of Boulder, Colo.

Total revenues for 1995 increased 18 percent to $1.9 billion from$1.65 billion the year before. Annual sales of Epogen, the red bloodcell booster used to treat anemia in kidney disease patients, rose 22percent to $883 million from $721 million in 1994. Neupogen, whichenhances white blood cell production in cancer chemotherapypatients, accounted for $936 million in sales, a 13 percent jump overthe $829 million in 1994.

For the fourth quarter of 1995, Amgen reported net income of $146million, or 52 cents per share. The earnings included a charge of $10million, or 2 cents per share, for licensing rights to Norcalcin fromNPS Pharmaceuticals Inc., of Salt Lake City. Norcalcin is an agonistto the calcium receptor on the parathyroid gland.

The 1995 fourth quarter net income was an 18 percent increase overthe last three months of 1994 when Amgen earned $121 million, or44 cents per share, excluding the Synergen charge.

Revenues for the fourth quarter in 1995 jumped 16 percent to $514million from $443 million in 1994. n

-- Charles Craig

(c) 1997 American Health Consultants. All rights reserved.