Penn faculty Daniel Skovronsky and Hank Kung received approval for their drug Amyvid on April 6. The drug will be used as a tool in diagnosing Alzheimer’s.

But Amyvid has received strong criticism from within Penn. Mateen Moghbel, a College junior and biological basis of behavior major, drafted an editorial backed by prominent researchers that questioned whether the drug can work.

The editorial challenged a mainstream theory in the field of Alzheimer’s: the amyloid hypothesis.

The tracer’s main purpose relies heavily on the theory. If amyloid plaque didn’t cause Alzheimer’s, there would be little use in testing patients for it.

And though the theory has a consensus among many scientists and doctors, it has yet to be proven. “At this point it’s likely that there’s some association but we can’t establish a causal relation between amyloid and the disease process yet,” Moghbel said.

Professor of Radiology Abass Alavi is also skeptical. “Amyloid hypothesis is only a hypothesis,” he said.

Moghbel pointed to disappointing results from several anti-amyloid drugs, putting the theory in question. “The anti-amyloid drugs that have been produced haven’t reversed cognitive decline,” he said.

Skovronsky admitted he wasn’t sure if removing amyloid plaque could really stop the progression of Alzheimer’s disease. In fact, he said, his own company produced a drug targeting amyloid plaque that actually hurt patient.

Development for the drug, which was intended to treat Alzheimer’s disease, had to be halted because it turned out to accelerate the disease’s symptoms and increase the risk of skin cancer.

According to Alavi, another challenge to the hypothesis is that some people with high levels of amyloid plaque, about 10 to 20 percent of them, never develop Alzheimer’s. “A lot of people who are perfectly normal are found to have amyloid deposits in their brain,” he said.

Moreover, the function amyloid plays in the human brain is still unclear.

Jorge Barrio, a specialist in imaging techniques for Alzheimer’s at the University of California, Los Angeles, argues that amyloid is actually necessary. “Amyloid is a normal component of the human brain,” he said. “Do you know any harmful things that you have naturally in your body?”

But Kung argued, amyloid is like cholesterol: though cholesterol does not necessarily lead to heart attack, it is still harmful, and a risk factor.

He said, drugs aimed at eliminating amyloid plaque will be beneficial, whether the plaque is a direct cause of Alzheimer’s disease or not. “There are at least 100 years of accumulated data, now we know amyloid is a very bad thing in your brain.”

Kung has high hopes for the future of Amyvid and amyloid imaging. “I certainly think this will eventually change the practice of how AD will be diagnosed.”

Penn professor of medicine and active member of the Alzheimer’s Disease Center Jason Karlawish is also cautiously optimistic. “I think, in the future, after more experiments are done, it could be revolutionary,” he said.

Still, in 2010 Avid decided to modify its FDA application, deleting a phrase that says amyloid plaque is a “defining pathology of Alzheimer’s disease.”

Skovronsky worries the tracer’s capacity to help diagnose Alzheimer’s may prove disappointing. “If there’s failure [people] will lose their excitement,” he said.

A lot of money has been invested in the amyloid hypothesis. According to the Wall Street Journal, the “lion’s share of financial support” in Alzheimer’s research focuses on amyloid.

In Dec. 2010, Eli Lilly bought Avid for $300 million. One condition of the sale was that Avid stockholders would receive $500 million in bonuses, conditional on Amyvid’s approval.

This may be a mixed blessing for investors. According to Forbes magazine, “Lilly shares have fallen 1.3 percent along with the broader market” after Amyvid obtained FDA approval.

The main reason, according to Forbes, is that the Centers for Medicare and Medicaid Services have not yet agreed to pay for the drug. Eli Lilly is pushing for a faster approval process for the reimbursements. Right now, the drug is poised to cost $1,600 a dose plus over $3,000 for a PET scan which will not be reimbursed either.

Another reason may be the lukewarm blessing from the FDA, which only approved Amyvid as a diagnosis tool in very particular instances. Forbes calculates the drug will produce less than $100 million in revenue per year.

Penn itself has stakes in Amyvid. It will receive “single-digit” royalties from the sales every year, until its patent runs out in about 10 years, according to Michael Cleare, the Executive Director of the Penn Center for Technology Transfer. “The money is secondary compared to the social benefit,” Cleare said.

Now that Amyvid is ready to enter the market, doctors are considering how the drug could change the way they treat and diagnose Alzheimer’s patients.

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