13 June 2012. Lilly is getting ready for prime time—and to cash in. Amyvid, the first FDA-approved Aβ imaging ligand, is now available to researchers within reach of 16 manufacturing sites across the United States, according to a June 1 press release by Eli Lilly and Company and Avid Radiopharmaceuticals, Inc. Online training for use of the ligand is now up and running, and in-person training began 11 June 2012, starting in Miami. Manufacturing, distribution, and the FDA-stipulated user training are gearing up, even as a task force convened by the Society of Nuclear Medicine and the Alzheimer's Association scrambles to formulate some expert guidelines on how amyloid imaging technology should be used in the clinic (see Part 2 of this series).

Amyvid—aka florbetapir—is the first to receive the agency’s nod among several imaging ligands that burst onto the clinical scene in the past eight years (see ARF related news story). Others include florbetaben from Piramal Healthcare, flutemetamol from GE Healthcare (see ARF related news story and ARF related update), and AZD4694 by AstraZeneca (see ARF related news story).These 18F-based ligands reveal amyloid plaques in positron emission tomography (PET) scans. The original compound, Pittsburgh Compound B (see ARF related news story), is widely used in research, but requires a nearby cyclotron because of its very short half-life.

States that manufacture the 18F-labeled compound at present include Arizona (Phoenix), California (Palo Alto, Colton), Connecticut (Hartford), Georgia (Atlanta), Florida (Fort Lauderdale, Orlando, Jacksonville), Illinois (Chicago), Missouri (St. Louis), North Carolina (Charlotte), Ohio (Columbus), Pennsylvania (North Wales), Texas (Dallas, Houston), and Washington (Seattle). With its half-life of 110 minutes, Amyvid must go directly to imaging centers from special radiopharmacies where it is produced. Imaging centers within a reasonable distance will be able to get the drug for now. (For instance, Boston centers will get their Amyvid from the Hartford center.) In the future, more sites will manufacture the compound.

An FDA advisory panel first rejected Amyvid back in January of 2011 (see ARF related news story) on the condition that Lilly improve the reliability among readers of the PET scans. In response, Lilly and Avid devised an online training program that takes some three hours. The company also teamed up with the American College of Radiology to train readers in person. A three- to five-hour program was launched in Miami on 11 June, with future sites to be announced later. Each program trains radiologists and nuclear medicine physicians who will read the PET scans. The company warns that physicians should not read the scans unless they have been trained; even then, some error may still occur when estimating plaque density, they say.

Amyvid's actual indication, as it appears on the product label, is "to estimate beta-amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer’s disease (AD) and other causes of cognitive decline." But big insurers have not yet decided whether, and in what instances, they will cover the scan. For example, if all diagnostic signs point to AD, will they pay for the scan? Will they reimburse for those in whom an AD diagnosis is uncertain?

Insurers usually follow the lead of the Center for Medicare and Medicaid Services (CMS). "We are aware of Amyvid and are having internal discussions about it, but have nothing to share publicly just yet," said a representative of the U.S. federal agency, based in Baltimore, Maryland.

Amyvid and other amyloid PET ligands will best be used to diagnose patients who present with confusing symptoms of dementia, said Andrew Budson, Boston University. "With some patients, it is difficult to figure out whether they have Alzheimer's disease or another disorder," he said. A scan of a person with documented memory problems showing little to no plaque would rule out AD. On the other hand, a positive scan does not automatically mean AD is the only etiology, Budson said. For example, a subdural hematoma could cause additional cognitive impairment even in the presence of AD plaques, and amyloid plaques are found in people who appear cognitively normal (see ARF related news story). For that reason, primary care physicians especially must be aware that this scan should be used in conjunction with, not in lieu of, other tests already in use for AD, said Budson. He stressed that, given the lack of disease-modifying treatments and a dearth of data on whether or not normal people with amyloid later become demented, those without memory problems should not get this diagnostic at this time. Despite inquiries from a reporter, Lilly would not divulge how it plans to market Amyvid. The Society of Nuclear Medicine (SNM) and the Alzheimer's Association have set up a task force to develop guidelines for using this technology (see Part 2 of this series).—Gwyneth Dickey Zakaib.

This is Part 1 of a two-part series. See also Part 2.