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Amgen Migraine Decision Looms, Maybe the Next Drug Price Fight, Too

Xconomy National — 

For some migraine sufferers, bright lights or loud sounds are enough to touch off an attack. For others, stress sparks the onset of pain. Bright lights, loud sounds, stress: Migraine triggers vary from one patient to another. But a common element is the abundance of a pain-inducing protein in the blood.

During a migraine attack, nerves release this protein, called calcitonin gene-related peptide (CGRP). A number of companies are developing drugs to block CGRP and stop migraine pain before it starts. The most advanced of these experimental migraine prevention drugs, from Amgen (NASDAQ: AMGN), is expected to receive an FDA decision Thursday. An approval will likely trigger the latest debate over pharmaceutical costs.

The last new class of migraine drugs entered the market nearly three decades ago. Estimates place the number of Americans who suffer from migraines at 28 million. Depending on coverage decisions that insurance companies make, many could be eligible for the CGRP blockers. But migraine is a chronic condition, and a drug to prevent migraine attacks would need to be taken on a regular basis—at considerable expense—for an extended period, perhaps even for life. Those factors have patients, physicians, and insurers paying close attention to emerging data.

“I imagine that these are going to be expensive,” says Gary Jay, a neurologist at the University of North Carolina at Chapel Hill. “I can’t imagine that an insurance company would say ‘no.’ But I also can’t imagine how much money a patient is going to have to pay.”

On Amgen’s heels are CGRP blockers from Eli Lilly (NYSE: LLY), Teva Pharmaceutical (NYSE: TEVA), and Alder BioPharmaceuticals (NYSE: ALDR), whose CEO unexpectedly stepped down two months ago as the company was working to bring its migraine drug to the finish line.

Some in the field believe competition could tamp down high prices. Jay was involved in clinical trials for sumatriptan, the first among the triptan class of drugs that were approved a generation ago. Jay recalls that sumatriptan carried a high price tag when it launched in 1991. Subsequent triptan approvals brought prices down, he says.

An influential drug-price watchdog notes that competition doesn’t always work that way in the drug industry. David Rind, chief medical officer of the Institute for Clinical and Economic Review, says physicians who treat hemophilia tell him that every time a new drug formulation becomes available, the prices go up. He also points to the 2015 launch of two cholesterol-lowering PCSK9 inhibitors, which were meant to be an improvement over widely prescribed statin drugs. The presence of a market competitor did not bring prices down. Instead, both drugs carried the same $14,000 price tag—which many insurers balked at paying.

“I don’t know what will happen with this,” Rind says of the new migraine drugs.

Some estimates that ICER has reviewed place the annual cost of a CGRP drug at $10,000 a year, Rind says. ICER has run a preliminary analysis, which found these drugs help patients reduce migraine attacks but, assuming an $8,500 annual price tag, would only be cost effective for patients who have more frequent migraines and have also exhausted other treatment options.

Healthcare expenses and lost productivity due to migraines cost an estimated $36 billion annually in the U.S., according to the Migraine Research Foundation, which is backed by Amgen, Lilly, and other drug companies. Rind acknowledges that migraine does have an impact on employers, but he says ICER’s analysis of the CGRP drugs focused on their value to patients. ICER plans to release a final version of its report, along with firmer pricing details, by the end of May.

Rind says Amgen and its peers aren’t saying yet how much they plan to charge for them. He has also spoken with insurance companies, who “are pretty nervous about these drugs,” Rind says. “Migraine is a common condition and if a drug comes on the market at many thousands of dollars per year, that will have significant budget impacts.”

EXPENSIVE PROTEINS

The expected higher price of the new injectable migraine drugs has another parallel to the new anti-cholesterol drugs. Both are proteins—monoclonal antibodies—aiming to replace or supplement pills, which are far cheaper to produce.

German firm Boehringer Ingelheim was the first to develop a CGRP-blocking migraine drug, but the company’s compound never advanced past mid-stage studies. Merck (NYSE: MRK) also developed CGRP drugs for migraine, but stopped work on them after Phase 2 results showed liver problems.

Amgen’s drug erenumab (Amovig) is a once-a-month subcutaneous injection. In Phase 3 studies lasting six months, patients experienced a 50 percent reduction in the number of migraines per month compared to patients given a placebo.

Triptans, the last new class of migraine treatments, were approved in the 1990s. Taken at the onset of pain, they reduce inflammation and constrict blood vessels to relieve symptoms. They do not work for everyone, and they do not prevent migraines from starting.

FDA-approved therapies for prevention are available, though none were developed specifically for the condition. Divalproex sodium (Depakote), initially approved in 1983 to treat epilepsy and later, bipolar disorder, is one such drug, as is the anti-seizure topiramate (Topamax). Beta blockers, a class of drugs for high blood pressure, have also gained additional approvals for migraine prevention. Botulinum toxin (Botox) injections offer yet another alternative, though the FDA has approved this therapy only for chronic migraine, defined as 15 or more headaches per month.

These drugs come with risky side effects, including nausea, fatigue, weight gain or loss, depression, and birth defects. They also take a while to kick in. Patients may need two or three Botox injections before they see any benefit, says Deena Kuruvilla, a neurology professor at Yale University. Anti-seizure and blood pressure drugs can take six to eight weeks to work.

“That’s a long time to be disabled by a migraine,” Kuruvilla says. “Our patients have to get back to work, get back to school.”

ASSESSING THE DATA

In clinical trials, all four of the new CGRP antibodies have produced relatively mild side effects, such as redness at the injection site. One of the lingering concerns has been cardiovascular risks posed by the drug. Those concerns appear to be eased by preliminary data Lilly released this week from a Phase 3 study testing its drug in episodic cluster headaches. Patients with cluster headaches tend to have greater heart risks, RBC Capital Markets analyst Brian Abrahams wrote in a research note. That no such problems were observed in the Lilly study offers “additional reassurance on safety for the CGRP class,” he added.

What’s more, these drugs also appear to have the advantage of working quickly. Kuruvilla notes that clinical trial results showed patients responded quickly to CGRP treatment. A subset of “super responders” who saw a benefit even faster would be particularly suited for CGRP therapy, says Wade Cooper, a neurology professor at the University of Michigan at Ann Arbor. The problem is, drug companies don’t yet know how to identify them ahead of time.

ICER’s analysis follows similar observations that CGRP treatment won’t be appropriate for all patients. Yale’s Kuruvilla says they’ll likely become one of many choices, perhaps as part of combinations, to treat patients. Patients could take a CGRP drug for prevention, she says, but when they need immediate treatment for an attack, triptans would offer an option, she says. Cooper says more options will help more patients.

“It’s such a different approach to treating migraine than we’ve had before, and the hope is it will help people that haven’t responded to other treatments,” he says.

Photo by Flickr user r.nial bradshaw via a Creative Commons license