After years of waiting, the U.S. nuclear medicine profession hasbeen granted access to tumor-targeted monoclonal antibody imagingagents for routine clinical use. Apart from its diagnostic benefits,monoclonal antibody technology offers the potential of
After years of waiting, the U.S. nuclear medicine profession hasbeen granted access to tumor-targeted monoclonal antibody imagingagents for routine clinical use. Apart from its diagnostic benefits,monoclonal antibody technology offers the potential of expandednuclear medicine procedures and equipment sales. Use of monoclonalscould be limited, however, by their high cost.
The Food and Drug Administration included approval of Cytogen'sOncoScint in its year-end flurry of activity. The monoclonal antibodyimaging agent is certified for use in detecting colorectal andovarian cancer. OncoScint is indicated for staging known cancersand monitoring suspected recurrent cancers (SCAN 1/29/92).
OncoScint thus becomes the first monoclonal antibody-basedproduct to win FDA approval for use in nuclear imaging. But althoughCytogen has won a head start on its biotechnology competition,the company must navigate a course fraught with obstacles to winclinical acceptance for monoclonal agents.
The FDA issued its ruling on OncoScint over three years afterPrinceton, NJ-based Cytogen filed its product license applicationfor colorectal applications of the product. The FDA pored overthe PLA for so long that some industry observers were beginningto wonder if monoclonals would ever win the agency's approval.
The novelty of monoclonal agents was undoubtedly a factor inthe FDA's cautious review of Cytogen's product. That the reviewended successfully is a stamp of approval not only for OncoScintbut also for monoclonals in general, according to George W. Ebright,Cytogen chairman and CEO.
"I believe the FDA understood that they were setting theparameters and approving in principle a whole platform of newtechnology," Ebright said. "I think they knew they neededto be very careful and look at this closely."
OncoScint garnered regulatory approval in several Europeancountries in 1991, but Cytogen and its European marketing partner,EuroCetus, a European unit of U.S.-based Chiron, found that lastyear's product sales of about $500,000 did not meet expectations(SCAN 10/21/92).
While oncologists and oncologic surgeons were enthusiasticabout OncoScint, nuclear medicine specialists were reluctant toperform procedures because of their unfamiliarity with monoclonalagents, Ebright said. The marketing campaign for OncoScint inthe U.S. will focus on familiarizing nuclear medicine specialistswith the product, through workshops and additional clinical trials.
Cytogen's marketing partner for OncoScint is Knoll Pharmaceuticalsof Whippany, NJ. Knoll is the U.S. subsidiary of Knoll AG of Germany,which in turn is owned by BASF AG (SCAN 5/22/91). Knoll has 45salespeople to handle hospital accounts and about 300 to sellto general practitioners. Cytogen fields a sales force of 20 dedicatedto hospital accounts.
Cytogen received a one-time milestone payment from Knoll forrights to co-promote OncoScint shortly after the agent was approved.The payment's size was not disclosed.
The payment increased Cytogen's 1992 revenues to $16.5 million(end-December), up 51% from the $10.9 million reported the previousyear. The company reported a loss for the year of $12.9 million,16% lower than the $15.3 million loss reported in 1991. The losswas 75 cents per share on 19 million shares outstanding.
Concerns about OncoScint's price tag could also present obstaclesfor the product. OncoScint kits will be priced at $425 a dose.The antibody must be linked to the indium-111 radioisotope Indiclor,which is sold separately and is manufactured by Amersham. Indicloris the only radioisotope licensed for use with OncoScint.
Indiclor will initially be priced at $350 to $380 a dose, accordingto an Amersham spokesperson. That is a discount on the regularlist price of $450 for the radioisotope. The discount price isbeing offered as an incentive to use the monoclonal.
The costs for the monoclonal antibody and radioisotope willbe added to existing charges for a nuclear imaging exam. The finalprice tag for an OncoScint procedure will put the monoclonal beyondthe reach of many nuclear medicine departments, according to Dr.Carol S. Marcus, director of the nuclear medicine outpatient clinicof Harbor-UCLA Medical Center in Torrance, CA. Marcus was a guestpanelist for the FDA's biological response modifiers advisorycommittee during its discussion of OncoScint.
"The problem with OncoScint is that it's going to be soexpensive that few people will be able to afford it," Marcustold SCAN. "My hospital does not have the money to buy OncoScint.I'm not going to be able to use this product."
Ebright maintains that OncoScint is relatively cheap for abiotechnology product and that OncoScint's ability to identifyand stage cancer is unmatched by any other imaging modality.
Cytogen must also deal with questions about human anti-mouseantibodies (HAMA), which are produced by patients who receivemonoclonal agents like OncoScint that are made using mouse antibodies.Studies have shown HAMA to reduce the effectiveness of subsequentmonoclonal doses, and about 30% to 35% of patients who receiveOncoScint develop HAMA.
Cytogen has submitted data to the FDA on repeat usage of OncoScintthat indicate that HAMA levels tend to decline over a six to eight-weekperiod, Ebright said.
"We don't really see that the HAMA is a big deterrentfor the use of this product," Ebright said. "We havedemonstrated that (OncoScint) is very effective in repeat useand we have even imaged in cases with existing HAMA."
What impact will monoclonal agents have on the number of nuclearmedicine procedures performed each year? It's too early to tell,but the impact could be significant, according to Mark Lamp, vicepresident of marketing and sales for nuclear medicine at cameravendor ADAC Laboratories.
"One agent won't cause a huge groundswell of proceduralvolume," Lamp said. "But this and other products combinedwill have a positive effect for nuclear medicine."
Other companies with monoclonal agents waiting behind OncoScintfor FDA approval were heartened by the agency's decision. Whilefew drug makers anticipate a torrent of FDA actions on monoclonals,many believe that OncoScint's days as the only approved monoclonalimaging agent are already numbered. One agent nearing the finishline is NeoRx's OncoTrac for small-cell lung cancer and melanomaimaging (SCAN 6/3/92 and 12/16/92).
"This approval is a clear signal that (FDA reviewers)are comfortable, that they've seen enough of (monoclonal agents)for a long enough period of time that they are confident thatpassing these things for approval makes sense," said PaulG. Abrams, NeoRx president and CEO. "I would expect thatthe approvals for other agents would follow without undue delay."