Wednesday, May 23, 2018

ALS patients losing time and hope as they wait for insurers to cover a pricey new drug


MAY 21, 2018
For the past two years, Sarah Benoit has been getting around with the help of a walker, waiting for a medicine that’s out of reach.

Benoit, a former congressional aide, has ALS, a fatal neurological disease that gradually causes muscle weakness and paralysis. As it progresses, she struggles to maintain a normal life, but holds out hope that a drug called Radicava — the first new treatment in 22 years — will slow her deterioration.

Unfortunately, she can’t get the medicine, even though her doctor prescribed it last fall.

Like an untold number of ALS patients, Benoit faces a conundrum. She can’t afford the $145,000 price of the drug
without insurance, but her insurance provider has denied access to the drug, even though it was approved by the Food and Drug Administration last fall for all ALS patients. And as time goes by, Benoit knows that she is losing a chance to delay the inevitable.

 “I’m getting slower and weaker. It’s becoming harder to shampoo my hair or use a pencil. My disease is progressing slowly, but it is progressing,” said Benoit, 36, who lives in San Bernardino, Calif., and was diagnosed with ALS nearly six years ago. “I think the drug would make it possible to be with my family longer. So, it’s frustrating.

“I do understand that it’s business. I’m realistic. The drug company wants money to cover research, which we need and I support,” she said. “And the insurance company wants to keep costs down. I get all that. But I am shocked at the cost.
There’s no two ways around it. And the last thing an ALS patient needs is hoops to jump through. Everyone is wasting valuable time talking to insurance companies.”

Certainly, there is nothing new about a high-priced medicine or insurers acting as impenetrable gatekeepers. In this case, the manufacturer of Radicava, MT Pharma, maintains that years of research expense must be recovered. And for their part, various insurers argue that coverage decisions, while nuanced, reflect legitimate criteria.

But the sort of battle facing patients like Benoit serves as a cautionary tale. Costly medicines can give rise to misplaced expectations for patients and doctors navigating America’s Byzantine health care system. And the problem is compounded by well-intentioned regulators trying to help desperate patients whose medical needs are unmet.

“The problem is the way the system creates incentives for both drug makers and insurers to act as they do,” said I. Glenn Cohen, a Harvard Law School professor who is an expert in bioethics and health law policy. “When you allow private insurers to make decisions with only a patchwork of state regulations, they will choose not to cover every drug approved by the FDA. And drug companies are for-profit entities that set prices based on market conditions. This is why you have debates over coverage.”

There is little debate, though, that Radicava marks a turning point in treatment.

ALS, or amyotrophic lateral sclerosis, attacks brain cells controlling muscle movement. Initial symptoms can vary. Some people experience weakness in their legs, or have difficulty grasping things or swallowing. There is no cure and the mean survival time is three to five years, although some patients live 10 years or more. About 20,000 people in the U.S. have the disease at any given time.

Radicava is far from a cure, though. The drug was originally approved as a stroke treatment more than a decade ago in Japan, where Mitsubishi Tanabe Pharma later tested it for ALS. The trial indicated the medicine could slow the decline in function — by about 33 percent — although as with many medications, the results can vary among patients.

The FDA, which has been under increasing pressure to approve drugs for unmet medical needs, was convinced to greenlight the intravenous medication in May 2017 as an effective treatment. Given the dearth of new ALS medicines for nearly a quarter-century, the approval was a big deal for patients and their families, who have been yearning for a salve.

“Understandably, this created a lot of excitement,” said Calaneet Balas, who heads the ALS Association, a national advocacy group, which receives funding from the manufacturer and launched the celebrated Ice Bucket Challenge four years ago to raise research money and awareness about the disease.

But for some ALS patients, the excitement has given way to frustration and bitterness as they encounter roadblocks to obtaining the drug. Over the past few months, a few patients have responded by creating online petitions to shame insurers. Others visit a Facebook page devoted to Radicava, where questions about cost and insurance coverage are interspersed with advice about usage and side effects.

Why is this happening? Let’s start with the price.

In Japan, the drug costs $38,000. The drug maker argued the $145,000 price tag in the U.S. reflects years of research and development investment, including clinical work used to win FDA approval for a small patient population, when compared with the number of stroke victims in Japan. And a follow-up study required by the FDA as a condition of approval may cost up to $125 million, which has to be recouped.

“We feel the price we came to was done very carefully, very thoughtfully, and fairly reflects out-of-pockets costs spent on this clinical journey, not opportunity costs,” explained Kevin O’Brien, vice president of market access at MT Pharma, the U.S. unit.
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He maintained internal estimates indicate about 90 percent of patients who are seeking Radicava have, so far, been able to obtain the drug, although this could not be independently verified. O’Brien also noted the drug maker offers a patient assistance program that provides up to $20,000 to patients who cannot obtain the drug through private insurance.

The price of the drug, however, does not tell the whole story.

Radicava must be infused 20 times a month indefinitely, which adds to the cost for insurance coverage, especially if infusion takes place at a clinic or infusion center. But one insurer maintained that the price is not the deciding factor in whether to cover the drug or how much coverage to provide in such circumstances.

“Are there drugs far more expensive than we think they should be? Yes,” said Dr. Michael Sherman, chief medical officer at Harvard Pilgrim Health Care, the second-largest health plan in New England. “But where there is an unmet need and clinical efficacy, we won’t deny drugs based on cost alone. Where you do see perceived inconsistent responses or flat-out denials are in cases where evidence is weak.”

This brings us to the FDA approval.

The agency relied on that one small clinical trial involving patients in Japan — not the U.S. — and then issued a blanket endorsement for the drug. Whether a patient is in the earliest or latest stages of the disease, the product labeling simply indicates the medicine is for ALS patients — period. In other words, all comers are welcome, or so it would seem.

But there are differing opinions about the value of the drug because the clinical trial had only 137 patients and it took place over just six months. Although the drug generated statistically significant results when compared with a placebo, the findings relied on a functional rating scale, which some health care providers argue is a largely subjective metric that is too imprecise to be wholly reliable.

“Can it slow down the disease? For some people, possibly,” said Dr. Jonathan Glass, an Emory University neurology professor. “But initially, it didn’t work so [the company] had to do a post-hoc analysis [of a smaller, secondary trial using a subset of patients]. I’m not arguing that it’s bad data. It’s just minimal data. And the key question is whether the data is good enough to approve the drug for everybody.”

Private insurers, however, are not always obligated to cover a drug or provide a set level of coverage following FDA approval. And in an age in which drug prices keep increasing — and price tags for the newest medicines seem to reach ever-higher levels — some say insurers are simply using well-honed gatekeeping skills in response to the cost for Radicava.

 “One can’t assume it’s not part of their calculus,” argued Balas of the ALS Association. “There are private payers that have not been following the label [in determining coverage]. Payers have not said to us informally or formally that cost is the issue. They point to the trial design. But if it were a third of the price, might they cover it? I don’t know.”

Right now, she said, the clinical trial “does give them cover.”

Nonetheless, one benefits expert suggested the barriers to Radicava coverage are out of the ordinary.

“Typically, what’s going to happen is carriers will follow guidelines associated with FDA approval, but they have the ability — if patients don’t meet criteria — to deny coverage,” said David Dross, the managed pharmacy practice leader at the Mercer benefits consulting firm. “But I haven’t seen that to a great extent. It does seem unusual if FDA approval was that broad.”

Many insurers are, in fact, approving Radicava — but only for ALS patients whose functioning matches some or all of the characteristics of the trial participants, whose disease is not as advanced. Their functioning is measured using a scale that rates the ability to conduct 12 different activities, including dressing, speech, swallowing, handwriting, walking, climbing stairs, and turning over in bed.

There is another hurdle. One criteria cited by insurers for determining coverage is when a diagnosis was made. Some insurers will pay for Radicava only if a patient was diagnosed within two years of seeking the medication. This automatically excludes patients, however slow or fast their disease may be progressing.

Sarah Benoit, for instance, was twice denied Radicava by Blue Cross California, which administers the Federal Employee Program through which she receives coverage. The insurer, which requires prior approval before agreeing to cover the drug, did not respond to requests for comment. The reason was that she did not pass yet another functional rating scale that is used in Japan, which her physician finds frustrating.

“It’s a piece of information that we can’t give them, because we don’t use that scale in this country,” explained Dr. Jeffrey Rosenfeld, a neurologist at Loma Linda University. “It was tested in another country so we have no experience at all with this drug. So when I get a denial, I will point out the FDA didn’t approve the drug with stipulations.

“I think they’re denying it because it’s costly — they’re trying to be prudent and provide the drug to patients who might benefit most. But we don’t have the experience to say it’s not worth the cost. Unfortunately, this fits into a pattern, perhaps, of a non-sustainable expense to the health care community.”
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Harvard Pilgrim, meanwhile, denied Radicava to John Welch, a former elementary school teacher from Medford, Mass., three times between September and March. The insurer said it initially did not have a coverage policy in place when it issued the first two denials. But the reason appeared to be his vital lung capacity, according to staff at Massachusetts General Hospital, where he is treated. At the time his physician first prescribed the drug, his reading was 78 percent, just a smidgen below the 80 percent cutoff.

Numerous appeals were filed. Ironically, by the time he was approved in March, his lung capacity had fallen to 63 percent.

This perplexing approach to coverage infuriates not only patients, but also health care providers.

In a letter to Anthem Blue Cross of California concerning one of her patients who was denied Radicava, Dr. Abirami Muthukumaran of the Cedars-Sinai Medical Center in Los Angeles wrote in vain that “there is no evidence that Radicava will not slow the progression of her disease in people who would not meet the inclusion criteria of the clinical trial.

 “The reason the trial was only able to see an effect in the rapidly progressing, recently diagnosed patients is because [the drug maker] only used a six-month follow up time, which would not be long enough to detect slowing of disease progression in patients who were declining more slowly either because that is the nature of the disease, or they were more advanced,” she wrote.

“The criteria cited by insurers, in some ways, do make sense — but for research reasons,” said Jennifer Lynne Scalia, associate site director at the Neurological Clinical Research Institute at Massachusetts General Hospital. “The company needed to study people who could live longer, breathe better, and function better to see how the drug performed.

“But for clinical practice, it does not make sense. John Welch is an example. Yes, there are some changes for the worse in his [lung] capacity, but he remains high functioning. Clinically, he might have benefited sooner if Radicava does slow the progression and his loss of breathing function. Theoretically, he could have remained high-functioning for a longer period of time. That’s why the FDA approved it.”

For Welch, the approval was bittersweet.

“I’m excited to finally get the drug, but my body is getting weaker and it won’t make a comeback,” he told us.

“Hopefully, it will stabilize. But I felt much better last September. I had strength in my legs. I think I would have had a better quality of life if I’d gotten it then. And I blame the companies. The drug company is going in for the kill. And the insurer looks at this like actuaries.”

His physician, Dr. Haatem Reda, a Mass. General neurologist, explains the frustration this way: “I don’t know that the drug has made a big impact in patient lives, but it’s a bit of hope. Unfortunately, the [insurance] process is difficult. He’s not unique. It’s been a struggle for a lot of my patients to get Radicava. Even for those who are eventually approved, they go through a grueling process.”

Others simply give up.

Jan Daily, 66, a former nursing professor at Capital University in Columbus, Ohio, was approved for treatment last fall, but could not find an infusion center to treat her for very long. Why? Some centers are unwilling to accept reimbursement levels from Medicare Part B, which covers specialized injectable and infused medicines, according to Peggy Clary, who heads patient care services at the ALS Association chapter in central and southern Ohio.

So Daily, who was already experiencing paralysis in her legs, considered home infusion and turned to Medicare Part D, but this meant she would be responsible for more of the expense — both the nursing services and the drug. And in this instance, Radicava is at a higher tier on the plan formulary administered by SilverScript, a unit of CVS Health. As a result, she despaired at the out-of-pocket costs.

“I thought, what did I have to lose? I was approved and I hoped the drug would slow the progress” of the disease, Daily explained. “But the copay would have been $7,000 per month. It was too much. I can’t afford that. It was a huge disappointment. Now, I’m kind of worn down. I worked hours and hours on this, and finally had to accept it wasn’t going to happen. Meanwhile, I’m progressing so quickly.

“The drug company drew a line in the sand, which then means my insurance company draws their line.”
For its part, MT Pharma maintains things are changing. As of this month, more than 2,500 patients have been treated with Radicava, according to a company spokeswoman. “We are making progress with these insurers,” said O’Brien.

One physician, meanwhile, describes the situation this way.

“In our system, I would contend that it’s justifiable to deny funding the drug for people who don’t fit into the categories that were studied by the manufacturer,” said Dr. Kenneth Patric, who sits on the medical policy committee at Blue Cross Blue Shield Tennessee, which covers Radicava but if only certain criteria are met.

“Or if the FDA uses a broader scope for approval, we may still disagree and say we’re not going to pay for it that way. FDA approval is a first step, but only one step.

“That said, I think our approach to the whole health care system in the U.S. sucks. In a different setting that’s not so profit driven, the rationale would be different and you’d have a different answer” for Radicava, he continued. “But it’s a money-driven system.”

This story was updated to note that MT Pharma provides funding to the ALS Association.

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