I

t looked like a surefire way to make billions.

A year ago, two new drugs that used a novel mechanism to drive down cholesterol levels came on the market, and were promptly crowned as blockbusters in waiting. Analysts estimated sales at more than $3 billion a year.

But the two drugs have been commercial flops, in part due to a complicated reimbursement system that has frustrated doctors, confused patients, and left the biotech industry worried about the implications for other high-priced drugs in the pipeline.

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“These launches so far are close to, if not the biggest, wastes of development and commercial investment in recent industry history,” said Geoffrey Porges, a biotech analyst at Leerink.

The companies behind the drugs — Amgen and the partnership of Sanofi and Regeneron — are spending hundreds of millions to promote their products but have reaped a mere fraction of that in revenue. “You don’t need to be in finance to know that that’s not a sustainable business proposition,” Porges said.

No one disputes that the new drugs, Repatha and Praluent, are excellent at lowering bad cholesterol, or LDL. They often succeed where the traditional treatment — an inexpensive class of drugs called statins — fails. The problem boils down to doctors who are reluctant to write prescriptions, insurers who are unwilling to pay for them, and drug companies that have failed to understand a fast-changing marketplace.

The failures could send a chill through the still-booming biotech business, which relies on the idea that the risky, expensive process of developing new drugs can one day pay off big.

The new treatments work by blocking a protein called PCSK9, thereby freeing up the body to clear out LDL lingering in the blood. In clinical trials, PCSK9 blockers were able to slash LDL cholesterol by more than 50 percent, even when added to a maximum dose of statin drugs like Pfizer’s Lipitor.

Cardiologists say the drugs could save lives. An estimated 15 percent of the roughly 74 million Americans with high cholesterol have alarmingly high LDL levels despite taking other drugs. Many would be candidates for the new treatments.

And yet the new therapies have only been prescribed about 120,000 times, according to data from QuintilesIMS, grossing just above $150 million combined in the past year.

Why aren’t they flying off the shelves?

For one, some doctors are hesitant to prescribe them until there’s more information said Dr. Pradeep Natarajan, a cardiologist at Massachusetts General Hospital.

Yes, the treatments lower cholesterol, but does that actually ward off heart attack and stroke? Long-term results on how PCSK9 blockers affect broader health and mortality won’t be available until next year.

Another hurdle: Getting insurers to pay for the drugs, which both have list prices of about $14,000 a year.

To secure coverage for a single patient, doctors must submit pages and pages of documentation to prove that patients have already tried at least two statin drugs to no avail, or that they have an inherited disorder that results in sky-high LDL levels. In some cases, the paperwork has more than 40 questions.

And insurers almost always say no.

Payers have denied more than 88 percent of first-time prescriptions for patients with commercial insurance in the past year, according to Symphony Health Solutions. For those on Medicare, the first-time rejection rate was about 77 percent.

And even after an average of five appeals, more than two-thirds of prescriptions still aren’t getting covered, according to Amgen.

“There’s absolutely frustration among my colleagues,” said Natarajan, who specializes in treating patients with particularly high cholesterol. “They’re writing prescriptions where they think [PCSK9 drugs] are indicated, and then payers are saying no.”

But the people doing the rejecting say they’re justified.

When PCSK9 drugs first won approval, doctors were writing prescriptions for patients who didn’t fall in the categories that the drug was approved to treat, according to Dr. Steve Miller, chief medical officer of Express Scripts. Companies like his are paid by insurers and employers to negotiate drug prices and determine which treatments get reimbursed.

PCSK9 therapies are expensive, and if the likes of Express Scripts don’t limit their use, it could cost society upward of $100 billion a year, Miller said.

That figure is “absurdly off-base,” responded Dr. Joshua Ofman, Amgen’s head of value and access. Payers cooked up a doomsday economic scenario to help negotiate rebates from drug manufacturers, Ofman said, and they’ve since instituted “a very onerous practice designed to keep patients from getting these drugs.”

If data that will roll out in the next few years prove that PCSK9 drugs save lives, both payers and drug makers expect them to be more widely used. Cardiologists say they’ll be quicker to write prescriptions if they can confidently say patients will be less likely to suffer heart attacks or strokes. And the price might even come down, as Pfizer expects to debut a PCSK9 inhibitor of its own next year, looking to steal market share from Amgen, Sanofi, and Regeneron.

But the squabble over cost, access, and availability is unlikely to end any time soon. And the fear among biotech insiders is that the commercial disappointment of PCSK9 therapies will imperil new cardiovascular therapies.

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The Medicines Company, a New Jersey biotech, is at work on a next-generation PCSK9 drug that could be dosed just twice a year instead of monthly or every two weeks. And Esperion Therapeutics, headquartered in Michigan, is developing a pill that attacks LDL cholesterol through another mechanism.

While each is years away from approval, the companies have been operating under the assumption that their drugs will be profitable if they can simply show they reduce cholesterol. The uphill battle with first-generation PCSK9 treatments suggests otherwise.

“The interesting question is whether the industry will continue to invest — and whether investors will continue to support — further development of drugs for these metabolic targets where very large studies [of health effects] are required at tremendous cost, and where the commercial return is disappointing,” said Leerink’s Porges. “I think there’s going to be some reconsideration of that if this trend continues.”

And that could have a downstream effect on patient care, said Dr. Steven Nissen, a cardiologist at the Cleveland Clinic.

“If I were the CEO of a major pharmaceutical company, and I knew I could not recover the cost of developing an innovative medicine, I wouldn’t do it,” Nissen said at the Cleveland Clinic’s Medical Innovation Summit this week.

Stuck in the middle are physicians and patients, waiting on the industry to prove its drugs are effective and wading through payer bureaucracy to actually use them.

“Limiting access because of cost is reasonable from insurer’s perspective, but from the patients’ perspective, they should be getting these medicines,” said MGH’s Natarajan. “I don’t think we’ve achieved that balance yet.”

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  • Still looking in the wrong areas after all these years. The whole cholesterol lowering bullshit industry is a scam. Look at the real culprits: processed food elavated blood sugars insulin resistance.

    • Agreed! These drugs are terrible but for some reason that thinking took hold among medical professionals. Once that “bull” gets taught in medical schools docs have a hard time letting go of the statin dispensing habit. There’s plenty of documentation out there discrediting statins but patients are afraid to stop taking that junk. Now the drug companies have come up with an “off-label” use by calling statins anti-inflammatories. After all, inflammation is bad for you. It certainly is,and is causative in coronary artery disease due to smoking, not fats. Spacedoc.com is a great website for info.

  • Shrinking middle class, jobs by the thousands headed to other countries, people with or without health insurance are choosing between food or NEW medications.
    Statins came out with serious side effects of cooking the liver and later stripping the body of CoQ10 enzyme.
    Rhabdomylosis has caused more harm than good by Statins. Hence pain management with opioids.
    Hype, marketing, we have this new drug, people aren’t buying into it as there was harm. Look no further than Baycol!

  • Keep in mind the market demand to lower cholesterol is changing. As time passes fewer and fewer patients buy into the LDL bad cholesterol theory in heart disease. Plus memories of bad side effects from statins are still fresh in the public mind. Nobody wants to be a lab rat for these new drugs.

  • The article says refusal to pay will cause drug companies to not fund the cost of development of new products. However, it previously says that the high cost is due to the cost of promoting the drugs, which often outstrips the development costs. If their product performs well, it shouldn’t need hundreds of millions in promotion costs.

    • Isn’t that the truth—another thing the writer forgot–isn’t advertising tax deductible, so maybe they’re digging into our pockets several ways–findling ways to not pay taxes-which leaves us to basically pay for their roads or how anybody wants to think- then digging into our pockets so their CEOs can have a golden parachute

  • No proven life benefit. Ten times the price of statins when they were under patent. Burnt once by unreported, severe side-effects of statins. Twice shy. What’s the surprise?

    • If it’s not recorded, it doesn’t happen. I kept going in, and they wouldn’t do a urine test, no bun-creatine. They just put general vague muscle complaints.
      Months later the doctor ordered a urine test- and he screamed what did I do to have black urine. He was putting down that I had rhamdomylisis from hiking and sent me to a specialist that sent me to PT. By that time, I couldn’t walk without assistence. Then I had a seizure in front of my PCP. He put down that I’m allergic to statins. That was removed from my chart this June. And I live in a state that is almost impossible to sue in and with liability caps.

  • As a sufferer of familial hyperlipidemia, PCSK9 inhibitors were an exciting development. Unfortunately, the main reason I haven’t been able to begin taking them is that my insurance provider denied coverage. Also of note is the means of administering PCSK9 inhibitors: they are injectables. This can be a turn off for some who are uncomfortable with consistent injection – although anyone with chronically high cholesterol would be used to getting blood drawn every six weeks or so.

    It should also be pointed out that while two versions of generic rosuvastatin were released in the past year, Harvard Pilgrim simply priced them at the same price as Crestor and increased the cost of Crestor – resulting in no savings for opting for the generic version. Overall, the price of having high cholesterol with no control over it (as is such with genetics) has been skyrocketing over the past year.

  • As a retired nurse who has communicated with patients for over 35 years, I agree that the heart of medication refusal is mainly due to costs especially for the middle class who are continually being squeezed out of the Middle! Something has to give in our medical treatments that would allow these new drugs and not only the stains but many others to become more affordable for the average patient. It is sad when Medicaid patients can get them and we are paying for that as well but we can’t afford. I hope in the near future change will take place with radical Government change of power!

    • Medicare does not pay for everything, and we have co-pays that are sizable.. A medicine must be on the Medicare Pharmetical Formulary list. Then many Advantage Plans have pharmetical formulary boards that feel free to modify a doctor’s prescription-change it to something else. Then a pharmacy gets a script for a high priced self-pay, and the pharmacy tries to do you a favor by getting your plan to pay for it. Then the medicine is disapproved by the local advantage plan formulary board, and the script gets lost. Hey, I needed that med! meanwhile my doctor and I are trying other self pays that just don’t work too well, and even put you in the ER and referred to a specialist.

      This is one of my favorites–GI clinic having meds scripts audited by the formulary board in an opiate witch hunt and reduce the NetWorks and Medicares costs. OK, I had a self-pay that was being prescribed by my GI. 6 weeks later, the GI nurses took it on their own to apprise this patient—I passed the phone to a student while I was on hold- I called GI 3 times a day, and my pharmacy twice. My PCP wasn’t supposed to take charge of this non-opiod script. I was in the ER, my classes left substitutes crying–My PCP wrote the scripts for me after that.
      This is just the tip of the medicare iceberg

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