CASE STUDY: Pharma, payers partner on real world anticoagulant analyses

If health care payers are going to cover the costs of novel therapies rather than generics then they need real world evidence to justify the expense – data that show paying for a higher cost drug will lower health care costs generally – and makers of novel oral anticoagulants (NOACs) have accepted the challenge.

Boehringer Ingelheim has partnered with US payer WellPoint to study the health care economics of NOACs and best practices for the treatment of patients with non-valvular atrial fibrillation (NVAF). And both Boehringer and its competitor Janssen presented real world data showing the treatment and cost benefits of their anticoagulants versus the decades-old generic blood thinner warfarin in mid-November during the American Heart Association (AHA) Scientific Sessions in Chicago, Illinois.

Johnson & Johnson's Janssen subsidiary and Bayer HealthCare co-developed Xarelto (rivaroxaban) and Janssen markets the factor Xa inhibitor in the US. Boehringer developed and sells the direct thrombin inhibitor Pradaxa (dabigatran). Both NOACs are approved to reduce the risk of stroke and systemic embolism in patients with NVAF.

Janssen's and Boehringer's analyses are crucial, because their real world data could be used to sway doctors comfortable with warfarin's well-established clinical history and to convince payers that there are both health care and economic benefits to reimbursing their drugs' costs. The ongoing reviews of real world data for NOACs serve as a case study, of sorts, for therapies in other major indications.

"If you are prepared to look past just pharmacy costs, it is possible for pharma and for payers to come to a mutual conclusion that innovation is worth investing in," Jeff Huth, Boehringer's senior vice president of managed markets, told Scrip in an interview regarding the German pharma company's new partnership with WellPoint and the payer's subsidiary HealthCore.

Boehringer and HealthCore, which helps pharma and medical device companies sift through WellPoint's real world data for research purposes, will look at how health care is managed for NVAF patients. It's the first project under a five-year research collaboration to identify and address unmet needs in populations of mutual interest. The partners will look for gaps in care and best practices for treating patients that improve both the quality and cost of care.

"We want to make sure that patients are using right products and, if not, make them aware of others that are available. We want to understand the impact on the total cost of care of a therapeutic," HealthCore vice president of research Mark Cziraky told Scrip.

Health economics at AHA

NVAF patients treated with Xarelto had shorter hospital stays and lower associated costs than NVAF patients treated with warfarin, according to a review conducted between May 2011 and December 2012 of real world data from 4,500 patients in Humana's health insurance claims database, which Janssen presented on 18 November at the AHA Scientific Sessions.

The mean number of days that patients were hospitalized for any cause was 2.71 days for people treated with Xarelto and 3.87 days for warfarin (p=0.032), and the mean number of days in the hospital for NVAF-related reasons was 2.11 for Xarelto and 3.02 for warfarin (p=0.014) – about a day's difference in both instances.

The mean number of all-cause outpatient visits also was significantly lower at 25.26 versus 35.79 visits (p<0.001). and="" cost="" of="" care="" –="" including="" inpatient,="" outpatient="" and="" emergency="" room="" visits="" –="" was="" significantly="" lower="" for="" xarelto="" versus="" warfarin="" at="" $12,274="" per="" patient="" versus="" $16,056=""><>

The only data point higher for Xarelto than for warfarin was ER visits: a mean of 0.92 versus 0.72 ER visits for any cause (p=0.114) and a mean of 0.48 versus 0.26 ER visits for NVAF-related reasons (p=0.004).

"The bump in ER visits is attributed to natural progression of the disease state," Janssen's director of cardiovascular scientific affairs told Scrip, who noted that Humana's database didn't show specific reasons for why patients were going to the emergency room.

Given the rising cost of health care, Dr Crivera said the Xarelto versus warfarin comparison of hospital stays and the use of other health care resources is important for providers, patients and payers.

"The cost of hospitalization for all causes was a mean difference of $2,000. When you add in the drug cost, it's comparable between the two groups," she said. "It helps doctors understand the overall cost of care, because there's a perception that warfarin costs pennies, so it's cheaper. But when you look holistically, you see that costs are higher."

Fewer bleeding events, strokes

The results of two real world data analyses of Pradaxa versus warfarin were presented at the AHA Scientific Sessions.

First, a review of data from 38,378 atrial fibrillation (AF) patients in two US health insurance databases (MarketScan and Optum) found a significant 25% reduction in major bleeding events and a numerical 23% decrease in strokes for people treated with Pradaxa versus patients who received warfarin. This analysis is ongoing.

Second, an analysis of more than 25,000 patients in the US Department of Defense (DOD) Military Health System database showed a significant 27% drop in strokes (p=0.032) and a numerical 13% decline in major bleeding events for Pradaxa versus warfarin (p=0.094).

The data could allay some fears for prescribers worried about reports of major bleeds for Pradaxa-treated patients. Boehringer announced earlier this year that it will pay $650m to settle about 4,000 product liability lawsuits related to the drug's bleeding risks (scripintelligence.com, 29 May 2014).

While major lower gastrointestinal bleeding events were 30% higher for Pradaxa-treated patients in the DOD database analysis (p=0.021), there were 35% fewer heart attacks (p=0.024) and survival was 36% better for patients who were given the Boehringer drug (p<>

Boehringer's Mr Huth said the company has looked in the past at the cost of warfarin compared with Pradaxa in terms of how strokes and major bleeding events add to the cost of patient care.

"The good news is that payers have recognized that. If you look at reimbursement positioning for all of the NOACs, payers have recognized that," he said.

Payer partnerships

Boehringer's collaboration with WellPoint and HealthCore will look beyond the number of strokes and bleeding events or the length of hospital stays in the area of NVAF.

"Clearly there are gaps in understanding the appropriate patient type for the new oral anticoagulants and understanding how patients are handled in real world care," Mr Huth said.

Boehringer and HealthCore will take a look at which patients are being treated with NOACs and warfarin, and which patients are better suited to one drug versus the other. The partners will try to understand why even well-controlled NVAF patients end up in the hospital and how to best prevent or treat those events.

Boehringer also has a multi-year agreement with Humana related to chronic diseases, including chronic obstructive pulmonary disease (COPD) and cardiovascular disease, and the company is looking at additional opportunities to work with payers on joint projects.

HealthCore's Mr Cziraky said WellPoint also is looking to improve its research relationships with pharma. Boehringer is HealthCore's second major pharma partner. The WellPoint subsidiary signed an agreement with AstraZeneca in 2011 to examine real world data in chronic conditions.

"We will look at common areas of interest with our partners. We'll look at gaps in information to make sure we're bringing the best treatments to our patients," Mr Cziraky said. "Health economics is a big part of it, but not at the cost of clinical impacts."

Pharma partnerships are meant to generate real world solutions that can be put into practice by health care providers.

Future implications

The work that Boehringer and Janssen are doing now to quantify the health care value of their drugs, both on their own and in partnership with payers, may be required for all new drugs going forward as global prescription medicine costs escalate past the $1 trillion per year level, according to a recent analysis from the IMS Institute (scripintelligence.com, 19 November 2014).

And it's in the best interest of pharma companies to work with entities that decide which medicines to prescribe or reimburse before private or public payers make those decisions on their own.

Fortunately for Boehringer, the UK health care system's recent independent assessment of Pradaxa's value to patients went in the pharma company's favor.

The National Institute for Health and Care Excellence (NICE), the government agency that decides which new therapies will be paid for by the UK's National Health Service (NHS), recently determined that the efficacy of Pradaxa was similar enough to the previously-endorsed Xarelto in the treatment and prevention of recurrent deep vein thrombosis and pulmonary embolism to justify reimbursement for the Boehringer product (scripintelligence.com, 31 October 2014).

NICE said that Pradaxa and Xarelto are welcome additions to the list of treatments options, "because they avoid the need for the monitoring and dose adjustments associated with warfarin."

But Datamonitor Healthcare's Victoria Hudson noted at the time that UK doctors, who are comfortable with warfarin and know how to manage the drug's risks, are still trying to understand stroke, bleeding and kidney function risks versus the benefits of treating patients with NOACs – a group of therapies that also includes Pfizer's and Bristol-Myers Squibb's Eliquis (apixaban).

As opposed to oncology, where drug prices are rising without a lot of analyses of the cost of innovative treatments versus the benefits, companies with treatments for NVAF appear to be ahead of the game.

Due to the lack of cost versus benefit analyses for cancer drugs, the American Society of Clinical Oncology (ASCO) is running its own assessments of newer therapies and plans to recommend which products doctors should be using to treat patients (scripintelligence.com, 3 June 2014). It's an assessment that payers are likely to consider in future reimbursement decisions.