THOUSAND OAKS, Calif. -- Neupogen, Amgen Inc.'s drug fortreating neutropenia, is on a pace to become biotechnology'sbrightest star. Beyond its sole FDA-approved use as an adjunctto cancer chemotherapy, Neupogen is being cast for a widerange of roles, from fortifying HIV-infected individuals totreating autologous bone marrow transplant patients.

Already the third-ranked biotechnology product in terms ofsales behind Genentech Inc.'s Activase and Amgen's Epogen,Neupogen is stirring perhaps the greatest excitement amongresearchers and physicians for its potential to reduce durationof neutropenia that afflicts many AIDS patients. Neutropenia isa condition characterized by a dangerously low level ofinfection-fighting white blood cells.

The drawback is that clinical trial results that might proveNeupogen's case as an AIDS treatment won't be complete forseveral years, analysts say. They don't expect Neupogen as anAIDS treatment to boost sales in the near term.

Besides AIDS, the drug is now in various clinical trials,involving more than 10,000 patients, for treating at least fourother conditions. Just 17 months since the FDA approvedNeupogen as an adjunct to chemotherapy, the drug generated$100 million in first-quarter sales. It is quickly closing in on itssister product, Epogen, which debuted in 1989. Epogenproduced comparable 1992 first-quarter sales of $111.1million.

"Epogen is well at maturity, with a 94 percent to 95 percentmarket penetration rate, but Neupogen is only at the beginningof its growth cycle," said analyst Franklin Berger of Joseph PhalLyon and Ross in New York.

At its current growth rate, Neupogen will likely overtakeEpogen's sales before year's end, Berger told BioWorld. Andthat projected sales gain for Neupogen is being driven by thedrug's sole approved use in chemotherapy.

Analysts have predicted that U.S. sales of Neupogen will reachroughly a range of between $425 million to $475 million in1992, with an additional $95 million to $130 million comingfrom overseas sales. By 1996, many analysts forecast U.S.Neupogen sales will surpass $1 billion, with total sales possiblyreaching $1.5 billion.

"Neupogen is successful because it has proved to be a safe drugthat is relatively easy to use both in research and incommercial use, " said Amy Berler, an analyst with of Alex.Brown & Sons in New York. "It will continue to be successfulbecause, unlike it's competitors, it has almost no side effects."

"The sheer quality of the product and the broad label for whichNeupogen is approved is making a big difference to salesfigures we are seeing for this drug," said Jacqueline Siegel, ananalyst with Hambrecht & Quist Inc. in New York. Sheestimates that $40 million of her projected figure of $475million for 1992 Neupogen sales includes uses of the drug otherthan cancer chemotherapy.

Berger of Joseph Phal figures that 15 percent of the $425million he predicts in 1992 Neupogen U.S. sales will come fromoff-label uses. Much of these off-label prescriptions may bewritten by physicians for AIDS patients. Such treatment costsabout $160 per week for the average AIDS patient, according tophysicians.

"There are huge numbers of HIV patients nationwide using it,"said Steven Miles of the UCLA Medical Center. Miles has usedNeupogen for AIDS patients since last December in clinicaltrials. "Used as an adjunct drug, Neupogen is the drug ofchoice," he said.

AIDS patients sustain damage to their bone marrow both fromHIV virus itself and treatments that are aimed at slowingprogression of the disease. According to Miles, Neupogenincreases tolerance to larger doses of drugs such as AZT andraises the white blood count.

Amgen expects to release early-stage results late this yearfrom HIV trials that it is conducting with the National Instituteof Allergies and Infectious Disease (NIAID), but GeorgeMorstyn, Amgen's vice president of clinical and medical affairs,predicted that it will take several years to obtain conclusivedata from the current Phase III trials.

Encouraging results from a National Cancer Institute study,using Neupogen as an adjunct therapy to the AIDS drug AZT, isscheduled for publication in the September edition of theJournal of Pediatrics. Phillip Pozzi, who conducted the study,declined to give details, but told BioWorld that it was successfulin determining optimum dosages of AZT that could be safelygiven to the children while maintaining white blood cell levels.

Children require higher dosages of AZT because the HIV virus,which causes AIDS, is more damaging to a child's centralnervous system (CNS) and can delay development. AZT canhelp children catch up developmentally, and higher AZTdosages are necessary to ensure that the drug enters the CNS.

According to Pozzi, the 19 children in the study could nottolerate the recommended four-per-day dosages of 120milligrams per kilogram of AZT without causing a decline theirneutrophil counts to less than 500. Using Neupogen allowed fulldoses of AZT to be administered.

Amgen officials are excited about Neupogen's potential, butnote that tapping that potential will require more clinical tests,most of which are being carried out independently of thecompany.

"Although it is primarily used in chemotherapy, it's a productwith great potential," said Gordon Binder, Amgen's chairman.

"Neupogen's a great drug which does exactly what it's meant todo," said Berger of Joseph Phal Lyon.

"Not only does it treat the side effects of chemotherapy well,but it also addresses dose-intensification-therapies, thosewhich allow increased chemotherapy due to Neupogen's abilityto maintain neutrophil count, thus enhancing doses of cancerdrugs. ... It's an exciting prospect for Amgen because aschemotherapy doses are able to be increased, so will the use ofNeupogen, "Berger said.

Neupogen still has plenty of relatively untapped sales potentialbeyond the oncology market, where Berger estimates about 85percent of specialists are familiar with the drug. Nowhere nearthat number of general physicians are, he said.

ADDITIONAL INDICATIONS FOR NEUPOGEN

Amgen intends to extend Neupogen's label to includeapplications for malignant therapeutics. Among the usesAmgen is pursuing in clinical trials are:

-- A protocol for Phase III trials is under way in patients withAIDS malignancies, such as lymphoma.

-- In Europe, HIV patients receiving AZT are being treated withNeupogen for neutropenia, a decrease in the number ofneutrophilic leukocytes in the blood.

-- Studies using Neupogen in infectious diseases are movinginto Phase III. Patients with low neutrophil count aresusceptible to serious infections. Early research has shown thatNeupogen improved neutrophil count and enhanced the use ofantibiotics.

-- Phase III trials are under way to look at the efficacy andsafety of Neupogen in myeloid leukemic colony stimulatingreceptors. Myleodystlastic syndrome and myeloid leukemiaaffect blood cell formation in bone marrow.

-- Neupogen is in U.S. clinical trials for use in autologoustransplantations. European regulatory agencies haverecommended approval of Neupogen for both autologous andallogeneic (from siblings) transplantation. The use of Neupogenin autologous transplantations can reduce recovery time ofneutrophils from three to four weeks to nine to 10 days.

-- Applications for approval for use of Neupogen in severechronic neutropenia have been made worldwide. Severe,chronic neutropenia is a rare disorder affecting small childrenand young adults who have low neutrophil counts andconstantly suffer from serious infection.

-- Michelle Slade Associate Editor

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

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