Piramal Hopes Depth Of Neuraceq Data Will Provide Contrast For Third Alzheimer’s Imaging Agent

Neuraceq will be the third entrant into the beta-amyloid imaging market, a space already limited by concerns about the clinical utility of PET scans in Alzheimer’s disease management.

Piramal hopes the depth of the data on Neuraceq, including the first regional histopathology analysis submitted in a beta-amyloid tracer NDA, will provide contrast with Lilly’s Amyvid and GE’s Vizamyl as it becomes the third drug to enter the Alzheimer’s imaging market.

Neuraceq is the first FDA approval for Piramal Imaging SA, the business established by the Indian firm following its acquisition of Bayer AG’s molecular imaging business in 2012.

FDA approved Neuraceq ([18F] florbetaben) March 14 for the same indication as Amyvid and Vizamyl: a radioactive diagnostic agent for Positron Emission Tomography imaging of the brain to estimate beta-amyloid neuritic plaque density in adults with cognitive impairment who are being evaluated for Alzheimer’s disease or other causes of cognitive decline.

Piramal touts the depth of its clinical trials as a point of differentiation. Like Amyvid and Vizamyl, Neuraceq’s NDA included comparisons of in vivo PET imaging data with post-mortem brain tissue. But Piramal went “one step further,” the company says, “providing a regional histopathology analysis as part of the application for the first time.”

“Defined regions obtained post-mortem were exactly matched to the images and assessments on tracer uptake were made in identical sections,” Piramal explained. By showing that Neuraceq binds to beta amyloid on both a regional level, by brain section, and at the whole brain, or subject, level, the trials produced more data points than other PET tracer trials.

“While not all of the data made the label, [FDA] included the subject-level (whole brain) visual analysis results and compared it with the regional histopathology analysis,” Piramal said. A scan is classified as positive if beta-amyloid neuritic plaques are “more than sparse” in any of the six regions, or is considered negative if none of the regions contains plaques assessed as more than sparse. A negative scan indicates a reduced likelihood of Alzheimer’s disease, but a positive scan does not establish a diagnosis.

The clinical usefulness of this information is still in doubt. While FDA has established and followed a pathway for approval of beta amyloid tracers, Office of Drug Evaluation IV Deputy Director Shaw Chen noted that “the correlations of amyloid imaging findings with the diagnosis, prognosis and response to treatment of Alzheimer’s disease have not been investigated” in a Vizamyl review memo (Also see "FDA Review Of GE’s Vizamyl Shows Caution In The Face Of Alzheimer’s Disease Unknowns" - Pink Sheet, 19 Feb, 2014.).

CMS has limited reimbursement of beta amyloid imaging agents to clinical trial patients under a “coverage with evidence development” process that aims to accumulate outcomes data (Also see "CMS Denies Lilly’s Request For Broad Medicare Coverage Of Amyvid In Draft Memo" - Pink Sheet, 8 Jul, 2013.). Despite opposition from patients and industry, CMS finalized its coverage decision Sept. 27, 2013.

Despite the tough reimbursement climate, the amyloid tracers keep on coming – Amyvid was approved in 2012, Vizamyl in 2013, Neuraceq in 2014. Navidea has another F18-labeled candidate, NAV4694, in advanced development. A Phase III autopsy-based trial started in the first half of 2013.

The radioactive PET tracers are manufactured and distributed by specialty radiopharmacies. Piramal partnered with IBA Molecular for Neuraceq in August 2012. IBA Molecular operates a network of 49 PET isotope facilities worldwide, 13 of which are in the U.S. Amyvid is partnered with PETNET Solutions, a Siemens subsidiary with 50 locations worldwide, and Cardinal Healthcare. GE operates its own GE Healthcare Nuclear Pharmacies network, which will launch Vizamyl in the U.S. in early 2014.