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Breast Cancer Test Makers React to Movement in German Reimbursement Process

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NEW YORK (GenomeWeb) – A contractor for the German government that evaluates new medical interventions has submitted the final draft of a report to regulators in that country, kicking off a review that could lead to reimbursement for gene expression-based breast cancer tests.

On Oct. 31, the Institute for Quality and Efficiency in Healthcare (IQWiG), an independent body that provides advice to the Federal Ministry of Health and to the Federal Joint Committee (G-BA), which decides what gets covered under Germany's statutory health insurance system, submitted its report on biomarker-based testing to inform treatment decisions for primary breast cancers.

The report is scheduled to be published approximately eight weeks after submission, or sometime in December, an IQWiG spokesperson told GenomeWeb in an email. Based on the report, some stakeholders expect the G-BA to make a decision about coverage of these types of tests, which include Agendia's MammaPrint, Genomic Health's Oncotype DX, NanoString Technologies' Prosigna, and Myriad Genetics' EndoPredict.

While the report's contents remain the subject of speculation, at least one test maker, Dutch molecular diagnostics firm Agendia, is expecting a positive general coverage decision next year and has moved aggressively to position its test accordingly. In January 2015, the G-BA already announced case-by-case reimbursement for gene expression-based breast cancers tests for select patients and in August, the committee approved reimbursement for genomic breast cancer tests when conducted in specialty outpatient centers.

Though a November 2015 preliminary report from IQWiG recommended the G-BA take no action on general reimbursement for the tests, due to a dearth of clinical data, representatives for Agendia and Genomic Health suggested that  there is more data available now.

In September 2015, researchers published preliminary data from the US National Cancer Institute's TAILORx breast cancer trial, suggesting Oncotype DX offered clinical utility in predicting which patients would benefit from chemotherapy. In line with the TAILORx early results, in August of this year, researchers behind the MINDACT trial published results in the New England Journal of Medicine, suggesting women with high clinical risk of recurrence, but low genomic risk, might be able to eschew chemotherapy.

In Agendia's eyes, the new data should lead the G-BA to approve general reimbursement. The MINDACT study used the firm's MammaPrint test to determine genomic risk of recurrence. "We have proven on the highest level of medical evidence that 46 percent of patients with high clinical risk have low risk with our test," Marion Wasmayr, Agendia's business development manager for Germany, Austria, and Switzerland, told GenomeWeb. "This probably will be the key necessary to turn this decision around. We are all very positive that this [reimbursement approval] will happen."

Wasmayr said that the firm expects a positive decision on reimbursement sometime in early- to mid-2017. With that in mind, the firm has launched a patient access program for patients covered by Germany's public health insurance, providing MammaPrint for free to patients who qualify.

Announced in October, but in effect since May, the Bridge program is meant to provide access to MammaPrint for patients who would not otherwise be able to afford the test. In Germany's healthcare system, patients covered by insurance companies, so-called sickness funds, under the public system, which covers approximately 90 percent of the population, do not currently have a way to get the test without paying out of pocket. Earlier this year, for example, recruitment into a clinical decision impact study (PRIMe) featuring the test had stopped much earlier than anticipated, leaving patients who could benefit from the test with few options to get it.

Agendia chose to implement a program to "bridge" the time period between the end of PRIMe study enrollment and implementation of reimbursement. It is working with the German firm Palleos Healthcare Services to administer the program, including the logistics of collecting samples from participating clinics and sending them back to Agendia for testing. As part of the Bridge program, Palleos is securing authorization from patients to pursue reimbursement for some cases that qualify under the per-case reimbursement strategy.

If Agendia is right about the G-BA's impending decision, the Bridge patient initiative could be a shrewd move to generate familiarity with the test in the German market. "It's a program enabling us to get business flying as soon as the reimbursement code is in place," Wasmayr said. "You have to invest in the market before you can get money out of this." The firm sees an opportunity to get key opinion leaders and patient advocates talking about MammaPrint.

Three other companies are positioned to compete with Agendia in Germany, should reimbursement become a reality. Genomic Health's Oncotype DX test would also come in backed directly by prospective study data from TAILORx. Myriad Genetics, which recently acquired Sividon Diagnostics and its EndoPredict test, and NanoString Technologies, which provides the Prosigna breast cancer classifier, are also potential competitors.

"We will see if all four will benefit from the [reimbursement] code or if it's just the tools that have prospective data," Wasmayr said.

NanoString CEO Brad Gray told GenomeWeb that he is "cautiously optimistic" the final report would lead to reimbursement, adding that the firm has seen progress for Prosigna uptake in Spain and France, which already reimburse for the test.

NanoString has previously noted that Prosigna has been included under treatment guidelines published by the German Association of Gynecological Oncology.

A Genomic Health representative added that Oncotype DX is the "first and only multi-gene breast cancer test with the highest (1A) level of evidence," under the AGO 2016 treatment guidelines.

Cologne, Germany-based Sividon, however, was "uninterested" in the Oct. 31 report, CEO Christoph Petry told GenomeWeb. As Myriad noted in a statement accompanying its third quarter financial results, beginning Aug. 10, the G-BA approved reimbursement for genomic breast cancer tests when conducted in specialty outpatient centers (ASVs). "The legal basis is there. The infrastructure is not quite there," Petry said. Breast cancer centers need to be designated as ASVs, but he expects "it's only a matter of a couple of months before a noticeable proportion of breast cancer centers are." Petry said Sividon is actively supporting clinics as they seek ASV designation.

If it happens, a positive decision for reimbursement would not be the end of the regulatory process. Another committee would still have to determine the reimbursement rate for genomic testing.

Wasmayr said that under the Bridge program, Agendia expects per-case reimbursement at several levels, from 100 percent reimbursement down to 30 percent coverage. MammaPrint's sticker price in Germany and Austria is €2,675 ($2,952). At best, the firm expects to receive reimbursement on a per-case basis for 20 percent of tests administered under the Bridge program, she said, with Agendia eating costs for all the rest.

"We cannot just sit back and wait until the code is there," she said. "Then we would be too late." According to market analysis performed by Agendia and shared with GenomeWeb, nearly 30,000 German breast cancer patients per year could qualify for genomic testing. There are approximately 75,000 new early breast cancer cases in Germany each year, Agendia said, with 70 percent being luminal type and 55 percent of those being high-risk luminal B cases. "All luminal high-risk patients should be tested with MammaPrint because 46 percent of them — about 13,000 — would not need chemotherapy, according to MINDACT results," the firm said.

Already, Agendia is seeing an uptick in samples processed worldwide since the MINDACT study was published. Wasmayr said the firm has had to scale up its laboratory capacity to cover the increased volume. "It's definitely growing," she said.