OncoScint MoAb skirts regulatory red tape

No one ever said being a pioneer was easy. Cytogen learned thisfirsthand after its most recent brush with radiopharmaceuticalregulations rendered obsolete by the development of monoclonalantibodies.

Cytogen was granted Food and Drug Administration approval latelast year for OncoScint, a monoclonal antibody-based nuclear imagingagent targeted at colorectal and ovarian cancer (SCAN 1/27/93).OncoScint remains the only monoclonal imaging agent on the U.S.market, despite expectations that the FDA's action would leadto a flood of other monoclonal agent approvals.

The responsibility for approval of monoclonal antibody imagingand therapy agents was transferred several years ago to the FDA'sCenter for Biologics Evaluation and Research from the Center forDrug Evaluation and Research. OncoScint was the first imagingdrug reviewed by CBER and received a product license application(PLA) instead of an investigational new drug (IND) or new drugapplication (NDA) certificate.

The fact that OncoScint received a PLA set the product at oddswith some state radiopharmaceutical regulations. Those regulationsare based on Nuclear Regulatory Commission rules stipulating thatonly products possessing INDs or NDAs can be used by licensednuclear medicine physicians, according to Dr. Carol S. Marcus,director of the nuclear medicine outpatient clinic at Harbor-UCLAMedical Center in Torrance, CA.

Marcus was a guest panelist for the FDA's biological responsemodifiers advisory committee during its discussion of OncoScint.

Because OncoScint uses an accelerator-produced radioisotope,indium-111, regulation of the product falls to state radiationcontrol agencies instead of the NRC. Some state regulations arebased on IND and NDA criteria, and a handful of states--includingTexas, Tennessee and Georgia--refused to allow physicians to useOncoScint until they paid a fee for a license amendment, Marcussaid.

The hold-out states eventually relented last month after publicpressure by the Conference of Radiation Control Program Directors,an association of the heads of state radiation control agencies.The NRC also advised states to approve OncoScint.

Since then the NRC has moved to rectify the problem by changingits policies. The NRC this month published proposed regulationsthat would allow NRC-licensed physicians to use drugs that areFDA-approved, regardless of the type of certificate granted, accordingto Marcus.

Since its FDA approval, Cytogen has taken a methodical approachto marketing OncoScint in the U.S. The company is building onits experience in Europe, where OncoScint received regulatoryapproval in 1991. EuroCetus, a European unit of U.S.-based Chiron,markets OncoScint in Europe. EuroCetus found early on that Europeannuclear medicine specialists were reluctant to perform monoclonalprocedures because of unfamiliarity with the agent (SCAN 10/21/92).

Cytogen and its U.S. marketing partner for OncoScint, KnollPharmaceutical of Whippany, NJ, sought to familiarize nuclearmedicine specialists with monoclonals by conducting an extensiveeducation campaign in the first three months after OncoScint'sU.S. approval.

The companies conducted 65 workshops across the U.S., trainingmore than 3500 nuclear medicine physicians, technologists andpharmacists in the use of monoclonals, according to James H. Geddes,group vice president of sales and marketing for Cytogen.

"The key to OncoScint's (future) success in the marketplacewas the need to do medical education with the nuclear medicinecommunity before we widely disseminated information and promotedthe product to referring surgeons and oncologists," Geddestold SCAN. "If (nuclear medicine physicians) don't know howto do the test correctly, we're not going to get the kind of resultswe know the test is capable of giving."

Cytogen has now begun actively marketing OncoScint to referringoncologists and oncologic surgeons, Geddes said. Cytogen has alsoapplied to the FDA to extend the shelf life on the product from24 to 36 months, but Geddes said that aging stockpiles are nota major problem for the company.

"I don't think the shelf life is a particular problem,and the reason is that most of the product is being ordered ona per-patient as-needed basis," Geddes said. "Thereisn't a lot of inventorying in the marketplace now."

BRIEFLY NOTED:

• Hitachi Medical Systems this month received Food and DrugAdministration 510(k) marketing clearance for its MRH-1500 1.5-teslaMRI system. It's been a long wait for the Japanese vendor: thesystem has been displayed as a works-in-progress at the last twoRadiological Society of North America meetings.

The MRH-1500 is an actively shielded superconducting magnetcapable of performing high resolution/high definition MR angiography,as well as fast spin echo and rapid gradient echo. The system'ssmall footprint allows it to be sited in an area as small as 650square feet, according to the company.

The first installation of the high-field unit is scheduledin August for a Florida-based radiology group, according to SheldonSchaffer, director of marketing for Hitachi Medical Systems America,Hitachi's U.S. joint venture company focusing on MRI and high-endultrasound sales.

Despite a tightening U.S. MRI market, HMSA's sales were stablein the first half of 1993 relative to the same period of 1992,Schaffer told SCAN. Although HMSA continues to install magnetsat freestanding imaging centers, the vendor's proportion of salesto hospitals has increased. Freestanding centers that purchaseMRI equipment are often owned either by national center chainsor hospitals, he said.

• Interspec reported this week that it has received FDAclearance to market the premium Apogee RX400 radiology ultrasoundscanner. RX400 is key to the Ambler, PA, vendor's drive into general-purposeradiology ultrasound sales from its primarily cardiovascular imagingbase.

The color-flow Doppler system offers high-resolution gray-scaleimaging with a series of wide-bandwidth transducers. Interspecis a supplier of transducer technology through its Echo Ultrasoundsubsidiary. Shipments of RX400 are expected to begin late thisyear.

• Berlex's Ultravist (iopromide) nonionic x-ray contrastagent was recommended for approval by the FDA's Medical ImagingDrugs Advisory Committee last month. The committee recommendedUltravist for eight indications, including CT imaging of the headand body and intra-arterial digital subtraction angiography.

Ultravist is the company's first nonionic low-osmolar agent.When approved, it will compete with Sterling Winthrop's Omnipaqueand Squibb Diagnostics' Isovue. Ultravist has regulatory approvalin 59 countries worldwide, according to the company. Berlex isthe U.S. subsidiary of Germany's Schering.

In other action, the committee also recommended for approvalDu Pont's technetium-tagged Neurolite single-photon emission computedtomography agent. Neurolite is indicated for brain perfusion studiesin stroke patients.

Amersham's technetium-labeled Ceretec is presently the onlybrain SPECT agent being actively marketed. Another brain SPECTagent, iodine-labeled Spectamine, has FDA approval but is no longerbeing marketed after supplier IMP shut down due to financial difficulties(SCAN 6/16/93).