Amgen Inc.'s Neupogen was approved for its third indication, severechronic neutropenia (SCN), the Thousand Oaks, Calif., companysaid Thursday.

SCN, a blood disorder in which the body fails to manufacturesufficient white blood cells, afflicts about 1,000 to 2,000 people inthe U.S., mostly children, Amgen said.

Neupogen, a recombinant granulocyte colony-stimulating factor, wasapproved in 1991 in various chemotherapy regimens and last July foruse in bone marrow transplantation.

Worldwide Neupogen sales were $719 million in 1993, and expectedto be some 10 percent higher in 1994. But the SCN approval is notexpected to impact sales figures.

"We expect it to be revenue-neutral, at best," David Kaye, Amgen'smanager of product communications, told BioWorld. "We are settingup an international disease registry which will track the course ofthese patients' treatments, and help physicians better under stand thiscondition. Any patient who participates will receive Neupogen at nocost."

Those with SCN do not produce enough neutrophils and are subjectto infections.

In clinical trials, 90 percent of those treated with Neupogendemonstrated complete or partial recovery of normal neutrophillevels. Kaye said the 120-person trial, which had a median age of 12,showed a 60 percent reduction in infections and 59 percent reductionin the need for antibiotics.

"The real significance is not the sales," Kaye said. "It's the impact onpatients' lives, and the fact that the FDA has approved the safe andeffective use of Neupogen in a chronic condition." Previousapprovals were in acute settings. _ Jim Shrine


By David N. LeffScience Editor

Gold and silver weren't the only treasures that the Spanishconquistadors brought back from the New World. Among the novelfoods they introduced to Europe in the the sixteenth century was thetomato.

In a typical recent year, the U.S. tomato crop sold for $1.626 billion.And genetically engineered Lycopersicon esculentum aims tobecome big business some day, with Calgene Inc.'s Flavr-Savrtomato already on the market and other companies moving in. (SeeBioWorld Today, May 19, 1994, p. 1.)

A chance discovery just reported in the current Proceedings of theNational Academy of Sciences (PNAS), dated Dec. 20, may or maynot resonate among biotech tomato cloners. It's title: "High a-tomatine content in ripe fruit of Andean Lycopersicon esculentumvar. cerasiforme: Developmental and genetic aspects."

The article's first author, plant cytogeneticist Charles Rick, whodirects tomato genetics resources at the University of California inDavis, found the unique cherry tomato genotype growing wild in anarrow valley on the eastern foothills of Peru's Cordilleranmountains. These pongos, or steep transverse gorges, cut through theAndean ranges to reach the Amazon basin.

Bitter Fruit From Peru's Outback

Rick had been systematically surveying Peruvian tomatoes duringthe 1980s, but until a road opened, he had no access to the remoteRio Mayo gorge, which runs for some 25 miles to join the larger RioHuallaga.

His PNAS paper notes that the one-of-a-kind plant variant he foundthere "deviates from the typical form of the entire species, includingcultivated tomatoes, in possessing high levels of . . . the steroidalalkaloid a-tomatine in its ripe fruits."

Rick deduced that this metabolite gives that local mutant fruit itspronounced bitter flavor, and "does not appear to affect adverselyeither the natives, among whom the bitter types are popular, orindividuals, including myself, who sampled the ripe, raw fruits inthis survey." He observed to BioWorld Today that "This experienceis reminiscent of the consumption in certain regions of `fried greentomatoes' without any manifestations of toxicity."

The plant scientist explained that, "as we determined in this research,all tomatoes have a fair amount of a-tomatine in the fruit, up untilthey start to ripen. Then the alkaloid degrades, and by full ripeness isdown to zero level. So eating green tomatoes is a way of ingestingtomatine."

This presumed ecological mechanism is missing in the Peruvianmutant, he pointed out, "and its persistent high tomatine levels wouldbe a detriment to the animals that would normally ingest and dispersethem."

The exotic Peruvian cherry tomato that Rick describes synthesizeshigh levels of tomatine early in setting its fruit, apparently to wardoff fungi and insects, as do tomatoes generally. But the wild RioMayo variant, unlike domesticated strains, doesn't decrease itsbitterness factor after ripening, to encourage predators to disperse itsseeds.

Hence, Rick concluded, "We don't deduce any evolutionary purposefor this kind of mutation _ unless there might be something subtlethere that we just don't know about."

Given its "very restricted geographic distribution," he commented,"mutation to this form appears to be a random event of doubtfulevolutionary significance." He found that its genetic determination"is totally recessive . . . and probably monogenic."

Rick observed that, besides its presumed anti-fungal and anti-insectproperties, "Tomatine may be of some interest for investigations onthe nature of tomatine catabolism, and it might have some potentialas a source of the alkaloid." But he added, "It has not got really intocommercial channels, and I don't see any big prospects for it." n

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