Repatha’s Path to Patients: Via Value?

amgen repatha

Amgen’s Repatha is “well tolerated” and a “welcome alternative” for some, admits the U.K.’s National Institute for Health and Care Excellence (NICE).  Yet, the British cost watchdog this week told Britain’s National Health Service (NHS) not to pay for the new super cholesterol reducer.

Repatha, one of the new class of biologic specialty drugs called PCSK9 inhibitors, reduces ‘bad’ low-density lipoprotein (LDL) cholesterol by 54 to 77%.  The European Commission and the U.S. Food and Drug Administration (FDA) approved Repatha and another PCSK9 drug, Praluent, this summer.

More Repatha Data

In a draft guidance set for final review in January, NICE disagreed with some of Amgen’s economic calculations and assumptions.  More significantly, it said direct evidence of Repatha’s impact on cardiovascular disease (CVD) outcomes was lacking and thus an “important limitation” and “key area of uncertainty.”

NICE could have used Repatha’s cholesterol-reducing results as a surrogate for CVD outcomes, based on biologic and epidemiologic studies of statins’ cholesterol-lowering impact on these outcomes.   In fact, the draft guidance allowed, “it was reasonable to infer that evolocumab (Repatha) would reduce CVD.”

However, NICE instead proposed a guidance review for February 2018, when results will be available from the long term, FOURNIER study documenting Repatha’s impact on CVD outcomes.   Short-term- study meta-analyses suggest considerable Repatha CVD effectiveness, possibly reducing mortality odds by 50%.

Pay for Performance

Meanwhile, a week earlier, back in the U.S., Harvard Pilgrim Health Plan decided not to wait for documented CVD outcomes.  In an exclusive agreement with Amgen, the plan negotiated a discount on the drug’s annual $14,100 wholesale price, plus additional discounts if Repatha delivers LDL reductions less than those observed during clinical trials.

Further discounts accrue if utilization exceeds certain limits, incenting Amgen to focus on patients who have an inherited disorder resulting in high levels of LDL cholesterol or have high-risk atherosclerotic cardiovascular disease conditions, such as heart attack or stroke, that have been resistant to treatment.

Harvard Pilgrim’s chief medical officer, Michael Sherman, told the Boston Globe that slightly less than one percent of the plan’s 1.2 million members would be eligible for Repatha.  He added that it was likely that even fewer would opt for the drug because it comes as a once or twice monthly injectable rather than a once daily pill.  The plan will also deploy rigorous utilization controls.

Sherman was coy when EP Vantage asked for more details on Harvard Pilgrim’s Repatha discount.  Was it close to an annual ‘care value price” – $7,735 for a cost effectiveness threshold of a willingness to pay $150,000 per quality adjusted life year (QALY)calculated by the Institute for Clinical and Economic Review (ICER) for the New England Comparative Effectiveness Public Advisory Council in which Harvard Pilgrim participates?1

“We’re not anywhere near that,” Sherman told Jon Gardner of EP Vantage.  “Ultimately, it was more about a negotiation, versus fundamentally agreeing that there’s a dollar value to [a QALY], which is where I’d like to be.  Maybe when there are other drugs on the market and more competition, we may get there.”

Express Scripts’ Deals

Mum, too, about exact pricing has been Express Scripts, which placed both Praluent and Repatha on its National Preferred Formulary in October after securing discounts from Amgen and the makers of Praluent, Sanofi and Regeneron.

This was after a July declaration by Express Scripts President Tim Wentworth, “while these drugs are being viewed as breakthroughs, they also have the potential to wreak financial havoc on clients who do not proactively manage.”

At Express Scripts, utilization management will come through a new Cholesterol Care Value program featuring “rigorous documentation” to ensure use only by clinically appropriate patients, who will get help with properly injecting the drugs and remaining adherent.

For plan sponsors enrolled in the CCV program, Express Scripts will cap total 2016 costs for the drugs.  It expects to spend $750 million on the drugs next year, lower than previous forecasts.  Among those earlier predictions was a ‘sky is falling’ alarm from CVS, which said costs could reach $150 billion annually if all coronary disease patients were included.

Before Express Scripts struck its PCSK9 deals, the company’s chief medical officer, Steve Miller, said the company would reference the ICER findings in its “negotiations with manufacturers.”  Apparently pleased with the result, Miller said the company received the best price possible and complimented the manufacturers for “collaborative discussions.”

During negotiations, Amgen, Sanofi, and Regeneron presumably repeated for Express Scripts their critique of the ICER methodology, specifically that it underestimated CVD risk, was not applicable to the population most likely to receive PCSK9’s and overestimated the population size likely to be treated with PCSK9’s.

Value Controversies

Amgen also explained that an alternative cost effectiveness model, which it is developing in alignment with the NICE model, confirms PCSK9 as cost effective at a QALY threshold of $150,000 or below.  In other words, Amgen believes the ICER ‘care value price’ of $7,735 (see above) should more accurately be $14,100.  The company notes that $150,000 is the value threshold recommended by the American College of Cardiology and the American Heart Association.

Meanwhile, back in the U.K., differential pricing is in play where the Repatha list price is £4,448.60 ($6,802.13), excluding an undisclosed patient access scheme discount.    Including the discount, the price Amgen proposed to NICE resulted in value thresholds ranging from a high of £78,879 ($119,903) to a most cost effective low of £22,902 ($34,813), depending on patient subpopulation and indication.

In stark contrast to the U.S., the QALY threshold over which NICE is less likely to recommend treatments for use in the NHS is typically between £20,000 ($30,393) and £30,000 ($45,590).  For the potential Repatha patients where the QALY threshold was within this range, NICE still decided to wait two years for more studies, the results of which are highly likely to show a CVD benefit.

Perhaps there is another reason for caution at NICE.  It is coming under pressure to lower the threshold to £13,000 ($19,759) – very different from the increasingly standard $150,000 in the U.S.  University of York’s Prof. Karl Claxton says that the current NICE threshold diverts funds from local health authorities and medical procedures, which he claims are more cost effective than new, expensive drugs.

Value or Values

NICE chief executive Sir Andrew Dillon countered, saying, “We need to think carefully about what’s being valued.”

“Concentrating only on QALYs means we are in danger of losing sight of other things that people, health systems and the government value very highly. This includes encouraging an innovative UK research base, or perhaps valuing more highly specific treatments that may be the only option for people with certain conditions,” Dillon added.

To advance Sir Andrew’s point, what is being valued depends on our values.  On that score, the negotiators at Amgen, Sanofi, Regeneron, Express Scripts and Harvard Pilgrim appear to have struck the right balance.

They are ensuring that the patients clinically most in need of Repatha and Praluent get the drugs by focusing on just those patients, while also providing financial support to those who might not otherwise get the drugs because of economic need.2

In human terms, only 28 people would need to be treated over five years to prevent a heart attack, stroke or death.  A “relatively low” number ICER admitted in its report.  Viewed another way by ICER, among CVD patients with high cholesterol, taking a statin and a PCSK9 together would prevent 5,621,800 heart attacks, strokes or deaths over a lifetime horizon.

Meanwhile, the U.K. waits.

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  1. When ICER initially announced its findings in early September, it highlighted and got the most headlines for an even lower, “value based price benchmark” of $2,177.  The key constraining assumption:  That health care costs should not grow any faster than growth in the overall national economy, which it estimated at +1% GDP growth.  After a series of calculations and further assumptions, ICER declared that the total annual cost of any single new drug could not exceed $904 million.  In other words, rationing.
  2. Groups such as AARP and editorial writers call for more public transparency in pricing agreements between payers like Express Scripts and manufacturers like Amgen.  However, the confidentiality to which buyers and sellers agree helps sustain a sort of differential pricing and access system within the U.S., i.e. ensuring the patients in clinical and financial need get the drugs they need.  Express Scripts negotiating with a manufacturer surely is a fair match.  However, where the match is not fair, i.e. when the buyer is a consumer, such as a consumer with a high deductible, then transparency is needed along with financial assistance.
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