OctreoScan becomes first peptide imaging agent to win FDA approval

Mallinckrodt product targets neuroendocrine tumors

Mallinckrodt Medical won Food and Drug Administration approval this month forOctreoScan, the company's peptide-based imaging product for detectingand localizing neuroendocrine tumors. Mallinckrodt thus becomesthe first company to receive regulatory approval for a peptideimaging agent.

Peptides have been promoted as cheaper, more effective alternativesto monoclonal antibody-based imaging agents such as Cytogen'sOncoScint (SCAN 6/30/93). Since its release last year, OncoScinthas suffered lackluster sales and many nuclear medicine physiciansbelieve peptides have the potential to succeed where OncoScinthasn't. The reality is likely to be more complicated. AlthoughOctreoScan faces fewer hurdles to commercial acceptance than OncoScint,the agent's success is by no means assured.

Mallinckrodt Medical of St. Louis received word of the FDA'saction on June 2, just three days before the Society of NuclearMedicine meeting in Orlando. Despite the short notice, the companywas ready to promote its new agent with a large booth displayand product literature.

It took the FDA 19 months to sign off on OctreoScan. This wasa relatively speedy review time compared to the agency's pacewith monoclonal antibody agents, some of which have languishedat the FDA for more than three years. The FDA gave OctreoScanpriority review because of the agent's ability to detect tumorsthat are difficult to diagnose with conventional imaging methods,according to Randy McBeath, senior product manager at Mallinckrodt.

OctreoScan is indicated for scintigraphic localization of primaryand metastatic neuroendocrine tumors bearing somatostatin receptors.The agent is composed of a synthetic version of the hormone somatostatin,which is linked to the radioisotope indium-111.

OctreoScan works by binding to somatostatin receptors producedby certain types of neuroendocrine tumors. These include pituitarytumors, islet cell tumors and paragangliomas. Mallinckrodt estimatesthat there are more than 80,000 new cases of neuroendocrine andsmall cell lung cancers a year.

OctreoScan will probably be used in cases where neuroendocrinecancer is suspected but has not been localized, according to Dr.Eric P. Krenning of University Hospital in Rotterdam, the Netherlands.For example, use of OctreoScan would be indicated if a patient'sblood chemistry test indicates a high level of certain types ofhormones produced by tumors, such as insulin or gastrin.

Because it is a peptide-based agent, users of OctreoScan willavoid several problems encountered with monoclonal antibodies.Peptides are much smaller than monoclonals, so they clear fromthe body more quickly and produce images with less backgroundnoise. In addition, peptides, being synthetic agents, do not sufferfrom human anti-mouse antibody (HAMA) response, in which the body'simmune system produces antibodies that can limit the effectivenessof repeat doses of monoclonals.

Peptides, like monoclonals, can be used in conjunction withtherapy agents that carry cancer-killing payloads directly totumor sites. OctreoScan's twin is Octreotide, a therapy agentthat also binds to neuroendocrine tumors. Octreotide has beenon the U.S. market for several years.

Despite the obvious benefits of peptides, Mallinckrodt stillfaces the challenge of winning the acceptance of the nuclear medicinecommunity. Like Cytogen, Mallinckrodt will launch an extensivecampaign to educate both nuclear medicine specialists and referringphysicians about targeted radiopharmaceuticals. There is no assurance,however, that Mallinckrodt will be any more successful than Cytogenin educating physicians about what is still considered an exotictechnology.

Mallinckrodt is also likely to encounter resistance to OctreoScan'sprice. Peptides have been touted as potentially cheaper than monoclonals,but OctreoScan will sell for $800 a dose -- only $25 less thanOncoScint. The medical community's resistance to the price ofOncoScint has been a major factor in the product's sluggish sales,according to Cytogen.

Even if Mallinckrodt does succeed with OctreoScan, potentialrevenues from the product will remain modest due to the limitedincidence of neuroendocrine tumors. The jackpot could come inexpanded applications for OctreoScan. Mallinckrodt is conductingclinical testing to support the use of OctreoScan for breast cancerand lymphoma.

Mallinckrodt's experience in moving OctreoScan through theFDA should pay off in receiving quick approval for expanded indicationsof OctreoScan, as well as winning regulatory clearance for newpeptide-based agents in development, according to J.L. Vanderheyden,associate director of nuclear medicine R&D.

"We hope that we have developed a path to fast approval.The material itself does not need to be reformulated at all tostart evaluating these indications," Vanderheyden said. "Webelieve we can apply a similar approach with other agents."