Only one amyloid PET scan will be covered to aid in the diagnosis of Alzheimer’s disease (AD), according to an official CMS decision on Friday. Limited coverage is offered with the stipulation of ‘coverage with evidence development’ (CED), which kicks off an undisclosed period of official CMS observation.

This CMS coverage decision follows the proposed decision memo that was released in July to the same effect. The new statement initiates a data-gathering phase through appointed CED clinical trials and perhaps through a registry much like NOPR (the National Oncologic PET Registry).

The memo states this decision was made due to insufficient evidence that amyloid PET provides a real benefit in the process of diagnosing AD and other neurodegenerative disorders. CED trials were presented as a way to expand on two areas of potential benefit: that amyloid imaging could help rule out AD in complicated scenarios that threaten misdiagnosis, for example in the case of frontotemporal dementia, which has similar symptoms, and to spur clinical trials in general for the development of new imaging agents and potential therapies for dementia.

"Based on a review of the medical literature, we feel that the evidence is insufficient to cover florbetapir unless patients participate in a CED trial," read a CMS statement regarding coverage of Amyvid, the first FDA-approved amyloid PET imaging agent, provided to Molecular Imaging via email.

The decision was based on the following factors as outlined by CMS:

• Florbetapir was able to demonstrate plaque, but plaque alone is not sufficient to document AD. There also must be neurofibrillary tangles and cognitive impairment in order to meet the gold standard of AD and florbetapir does not detect neurofibrillary tangles.
• Some studies showed the presence of plaque, indicating possible AD, but no post-mortem exam was done to confirm it, and some patients have tested positive for plaque, but don’t have AD.
• Even with the presence of plaque, the management of patients was inconsistent based on this finding. Some studies revealed that patients with positive test where not treated appropriately with AD drugs. Also studies showed that some patients who had a negative test, but were on AD meds prior to test, were kept on the AD meds.
• Some of the studies had a low number of participants, with not enough subjects to show the true degree of association between AD and the imaging studies.   

Statements expressing disappointment are being released by a number of amyloid imaging stakeholders, including the Society of Nuclear Medicine and Molecular Imaging and Eli Lilly, makers of Amyvid.

While noting that at least the CED is a start that offers some coverage, SNMMI reiterated there is extensive research already available from the development of appropriate use criteria by a taskforce of leading researchers.

“SNMMI appreciates that in its final decision, CMS included CED with short-term outcomes related to changes in management,” wrote SNMMI officials. “A test that can rule out Alzheimer’s disease can result in patients being taken off powerful medications that can be costly and are not indicated for their condition. That is a positive outcome. Although Alzheimer’s disease is the leading cause of memory loss, several other factors—such as other neurodegenerative diseases, strokes, thyroid problems or medications—can cause similar symptoms.”

The producers of Amyvid took a harder line, accusing CMS of overstepping its own authority.

"This final decision is not only contrary to expert opinion and published Appropriate Use Criteria previously recommended by the Alzheimer's Association and the Society of Nuclear Medicine and Molecular Imaging, but contradicts the statutory authority CMS has over coverage determinations for diagnostics,” wrote Eli Lilly company officials via release. “Denying appropriate patient access is also in conflict with the administration's National Alzheimer's Project Act. CMS participated in creating this plan aimed at developing new and innovative ways to diagnose, support and treat patients suffering from Alzheimer's Disease—yet the same agency is challenging the value of the only technology approved by the Food and Drug Administration (FDA) for estimating beta-amyloid neuritic plaque density in the living brain, which can aid in helping doctors make a more informed diagnosis."

After a period of data collection, during which amyloid imaging will be analyzed for its value in improving health outcomes across different patient cases and demographics and for its ability to engender new research and avoid futile treatments, CMS will announce a new coverage decision.

The Alzheimer’s Association and other stakeholders will be conducting a teleconference regarding the CMS decision on Thursday.