Last week on January 20, 2011, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee decided not to recommend approval of Lilly’s Amyvid™ (florbetapir) in a 13:3 vote. Florbetapir is an imaging agent used with Positron Emission Tomography (PET) to show accumulation of beta-amyloid plaque in the brain. I previously wrote about Lilly’s acquisition of Avid Radiopharmaceuticals for florbetapir on this blog.
This imaging approach aids in the early detection of Alzheimer’s disease, as a negative scan, not showing any beta-amyloid plaque, would rule out Alzheimer’s disease. Given that it is currently, hard to distinguish age related memory less and different types of dementia, diagnostic imaging tools have an important role to play.
The FDA advisory committee’s decision would probably have come as a surprise to Lilly, since the clinical trial data showed clear efficacy and no safety concerns. While the committee rejected immediate approval, they did recommend approval (16:0), conditional on a training program to show that radiologists and readers of the scans could be accurate and consistent in their image interpretation. The FDA is not bound by the Committee’s recommendations but is required to take them into consideration when deciding whether to grant approval.
Imaging is becoming increasingly important in clinical trial design. In therapeutic areas such as osteoporosis, rheumatoid arthritis and oncology, imaging end points are often surrogates for drug efficacy.
The challenge that emerging biotechnology companies face in linking imaging to drug use, is the variability of readers outside a controlled clinical trial environment where images may be read centrally. Standardization of image acquisition and reading needs to take place, so that a radiologist in different hospitals can come up with the same findings. Those involved with imaging clinical trials know how hard this can be, even within the controlled clinical trial setting.
The recommendation of the FDA advisory committee that Lilly needs to put in place a training program to show accuracy and consistency of readers is a valid concern and one that all biotechnology companies and pharmaceutical companies should take note of when developing imaging agents.
A company I have been watching for a while is Philadelphia based Avid Radiopharmaceuticals, now a wholly owned subsidiary of Lilly. They have a novel imaging biomarker, florebetapir (18F-AV-45) in development for the detection of Alzheimer’s disease.
In a press release last week, Lilly announced that the FDA had assigned a priority review to the marketing application of florebetapir. The Peripheral and Central Nervous System Drugs Advisory Committee of the FDA meet on January 20, 2011.
Bayer have a competitor product in development, forebetapen (BAY 94-9172). Both florebetapir and florebetapen are 18F radiolabelled imaging biomarkers that bind to amyloid plaque in the brain. When used in conjunction with a Positron Emission Tomography (PET) scan, they enable the accumulation of amyloid that occurs in Alzhemeir’s disease to be visualized.
Phase 3 trial results for florebetapir published earlier this year showed that the brain amyloid burden seen in the PET scans positively correlated with the plaques seen in autoposies of the same patients. Proof that what the imaging biomarker shows is an accurate representation of the underlying pathology.
What makes the use of florebetapen and florebetapir interesting is that it is already common practice to use imaging tracers with PET scans. Fluorodeoxyyglucose (FDG) is widely used in the diagnosis, staging and treatment of oncology patients as a result of its ability to show the intense glucose uptake that occurs with most cancers.
Both Avid and Bayer products are most likely to be approved based on the clinical data presented to date. It will be interesting to see the prices that they intend to charge.
As for the market opportunity, they are likely to have a role to play in the early diagnosis of patients with mild cognitive impairment, since at present it is difficult to diagnose these patients and differentiate Alzheimer’s disease from other forms of dementia. Most likely, models will be developed that look for a correlation between accumulation of amyloid plaque and decline in cognitive function, from which a probability of developing Alzheimer’s disease can be calculated.
Imaging biomarkers are likely to place an increasingly important role in the development of new products by biotechnology companies and in the design of clinical trial endpoints.