The Three “A’s” of Treatment Options:  Approved, Accessible and Affordable – Market Access Implications of Big News from ASCO 2014

By Debbie Warner
 

Over the course of five days during ASCO 2014, data from hundreds of clinical trials were shared.  Arguably, Phase III data garner the most attention as it usually answers the question: “Is there a new treatment option for cancer patients?” However, Phase III trial results provide only part of the answer until the FDA determines whether or not to approve the drug for the studied indication. Increasingly, the FDA doesn’t have the final say on whether the drug in question represents a viable treatment option for potential patients. Payers, too, are exerting influence over treatment options through prior authorization requirements that must be met for coverage to be approved, as well as patient cost sharing, which can threaten affordability of the treatment. In an era when the cost of a course of therapy with branded cancer drugs is typically measured in the tens of thousands of dollars and, not infrequently, over $100,000, FDA approval is no longer sufficient for treatment selection. Accessibility and affordability have become essential considerations as well.

In the May 2014 edition of OBR Green,1 Arnold DuBell, PhD, MBA, a consultant in Oncology Clinical and Scientific Assessment for Kantar Health, highlighted 10 abstracts anticipated to draw high interest at the conference. Among these were abstracts reporting of data on the currently marketed drugs Avastin®, Erbitux®, Yervoy®, and Imbruvica®. The range of outcomes represented by these trials, from the impressively positive data for Imbruvica in relapsed/refractory chronic lymphocytic leukemia (CLL), to the draw between Avastin and Erbitux, represent a range of market access implications as well as clinical ones.

CALGB 80405:  Fodder for Prior Authorization and Pathways?

The results of this large, Phase III trial were widely anticipated to elucidate conflicting data presented at ASCO in 2013, which demonstrated a survival benefit of Erbitux over Avastin in the first-line treatment of KRAS wild-type colorectal cancer (CRC)2 in the absence of a progression-free survival (PFS) benefit. Although the frequency of KRAS mutation in the U.S. population of CRC patients is 34%-38%,3 only 8% of metastatic patients receive Erbitux in the first-line setting.4 Three-quarters of the oncologists surveyed by Kantar Health in April 2014 indicated that payers require KRAS testing for prior authorization of Erbitux. Further, while oncologists experienced more reimbursement challenges for Avastin than for Erbitux (likely driven by greater volume of Avastin use), they were more likely to change Erbitux to a different treatment choice.5 Less than 50% of oncologists test for the KRAS mutation in first-line.3 While KRAS testing is critical for identifying patients likely to benefit from Erbitux, it adds cost, time and administrative burden to oncology practices selecting Erbitux, especially for first-line treatment.

Treatment pathways are becoming a more prevalent means of managing cancer treatment, and CRC is one of the three most common cancers to be the subject of pathways. Whether initiated by payers or practices, treatment pathways are designed to drive selection of “preferred” treatment modalities and products. While the definition of “preferred” is highly individualized, these products generally represent the most cost-efficient, evidence-based means of treating patients at each line of therapy. While demonstrated efficacy is usually paramount, tolerability and cost are also given critical consideration. When clinical outcomes are comparable, cost is usually the most important driver. For pathways developed within practices, commonplace especially in large oncology practices, administrative burden and patient affordability are also important factors.

The secondary but important factors of cost and administrative burden already favor Avastin over Erbitux, and prescribing patterns clearly show a preference for Avastin over Erbitux in first-line, even in patients with the KRAS mutation. The lack of difference in efficacy between Avastin and Erbitux revealed in CALGB 80405 presumably removes the clinical efficacy rational for selecting Erbitux in the first-line setting. Payers, already targeting Avastin and Erbitux for utilization management, may further leverage prior authorization to not only require biomarker testing for KRAS but also the use of Avastin before the more costly Erbitux will be covered. Such action may prompt practices to avoid the administrative burdens associated with Erbitux use. Pathways will likely be leveraged by both payers and oncology practices to further solidify the dominance of Avastin in first-line CRC.

EORTC 18071:  How Much of a Good Thing is Too Much?

Malignant melanoma is infamous for its poor prognosis. When Yervoy launched in 2011, it represented not only improvement in median overall survival but also the chance at long-term survival for some patients. However, this clinical benefit came with an unprecedented (at the time) price among cancer treatments of about $100,000 to $120,000 for a four-cycle course of treatment. In the 2012 Kantar Health Oncology Market Access oncologist survey, Yervoy along with Provenge® were the drugs most frequently cited by oncologists as being targeted by payers. By 2014, fewer oncologists cited Yervoy as one of the most payer challenged IV cancer drugs, though it remains among the top five. Payers, however, are not the only stakeholders sensitive to the cost of Yervoy. Nearly a third of practice managers identified Yervoy as the treatment most likely to have patients referred to the hospital for treatment for strictly financial reasons. Among them, carrying cost to the practice and out-of-pocket cost to the patient were the most frequent financial reasons for referral.

 

The Three “A’s” of Treatment Options:  Approved, Accessible and Affordable – Market Access Implications of Big News from ACSO 2014 (continued)

The strong positive recurrence-free survival data reported in EORTC 18071 for stage III melanoma patients receiving adjuvant treatment with Yervoy represents a significant advance in treatment, especially considering the limited treatment options and low survival rates for patients whose disease recurs. Few would argue that these outcomes are a very good thing for patients. However, the treatment cost per cycle in the adjuvant setting is more than three times greater than for the current indication of metastatic disease, due to higher dosing. Further, treatment continues after the initial four rounds with maintenance infusions every three months for up to three years. At the current WAC price of Yervoy, a first year of adjuvant treatment will likely exceed $300,000, a cost likely to spark renewed scrutiny among payers. Until Yervoy receives an FDA indication or National Comprehensive Cancer Network (NCCN) guideline recommendations (level IIb or higher), oncology practices are likely to experience claims rejections due to a dose in excess of the indication. Even if or when payers do reimburse for adjuvant use, practices will be waiting 90 days or more to get reimbursed the $50,000 to $60,000 for a single round or treatment. Patients with coinsurance on their medical benefit will incur over $1,000 in out-of-pocket cost for a single round of treatment. It is not unreasonable to expect oncology practices to seek alternatives to buy-and-bill reimbursement for adjuvant treatment of melanoma.

RESONATE:  Will it be the Gleevec® Story all Over Again?

Gleevec® was launched in 2001 at a price of $2,200 per month, a moderate (10%-20%) premium to the standard of care at the time, interferon.6 Hailed as a “miracle drug,” its price was unprecedented for a pill. Gleevec has a current WAC price of $7,660,7 comparable to many other oral TKIs. However, unlike many other TKIs that increase median overall survival and PFS by a few months and whose value for the cost is frequently called into question by payers, Gleevec is usually cited as the exception. By increasing the estimated 10-year survival from less than 20% to above 80%,6 payers often refer to Gleevec as a cure for chronic myeloid leukemia (CML) and rarely question its value.

Fast forward 12 years to November 2013, when Imbruvica was launched with an indication in the rare mantle cell lymphoma at a cost of $130,000. The Wall Street Journal speculated that “Imbruvica's cost could raise eyebrows even among doctors accustomed to high prices for many drugs.”8 Three months later, Imbruvica received approval for relapsed/refractory CLL, though at a lower cost of $98,400 due to the lower dose. However, there are four times as many CLL patients than MCL patients. Imbruvica received its indication based on an open-label Phase II study and proved its efficacy in the RESONATE trial, a Phase III study comparing it to Arzerra. Imbruvica was associated with a 78.5% reduction in the risk of relapse and a 56.6% reduction in the risk of death. These results conceivably place Imbruvica in a similar category of perceived value as Gleevec when payers consider the degree of efficacy provided, even at a cost nearing $100,000 per year.

However, the CLL market is growing increasingly crowded. Unlike when Gleevec launched, payers now have specialty tiers and differential formulary placement as tools to steer utilization or perhaps stimulate competitive contracting. Another important consideration is that Imbruvica competes against several different IV therapies, most notable Rituxan® plus Treanda®, which far surpasses Imbruvica use in both first- and second-relapse CLL.4 In addition to habit and familiarity, Imbruvica will have to overcome two additional factors. First, infused drugs still represent the dominant source of revenue for oncology practices. Secondly, patients are more likely to encounter very high cost sharing with orals compared with injectable drugs. While Pharmacyclics and Janssen Biotech have established a robust financial assistance program, 60% of CLL patients have a Medicare Part D drug benefit,9 making them ineligible for manufacturer financial support. While several not-for-profit copay foundations have CLL funds, donations to the funds may not be directed to specific drugs. 

Closing Thoughts

We are in an exciting era of clinical development of cancer treatment. Oncologists and hematologists have an unprecedented array of tools at their disposal to extend the lives of cancer patients. Biopharmaceutical companies have invested countless years and billions of dollars to bring these drugs to market. This investment and the unmet needs that these drugs address are reflected in high prices that are driving explosive growth in spending on cancer care. Not only do physicians have more “tools in their toolbox,” but payers have a growing armamentarium of tools at their disposal to help rein in the cost trend. Be it through pathways, prior authorization, formulary tiers or cost sharing, payers will continue to leverage these tools to exercise influence over drug selection and utilization. Clinical evidence is and will remain the single most important determinant of access in the U.S., but the evidence can no longer be viewed in scientific isolation. Not only payers but also patients and physicians will weigh the evidence within a broader value context that takes price, therapeutic alternatives, and outcomes into account.

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About the Contributor

Debbie Warner is Vice President of Commercial Planning at Kantar Health.

Kantar Health is a leading global healthcare advisory firm and trusted advisor to the world’s largest pharmaceutical, biotech, and medical device and diagnostic companies. It combines evidence-based research capabilities with deep scientific, therapeutic and clinical knowledge, commercial development know-how, and marketing expertise to help clients launch products and differentiate their brands in the marketplace.

Kantar Health’s oncology-related offers include Oncology Conference Insight, client-directed oncology conference coverage that analyzes the most important research at significant oncology meetings; and

CancerMPact® Treatment Architecture, which assesses the current clinical management of cancer patients by site and stage for all treatment modalities.

If you would like us to act as catalysts for you, contact us at www.kantarhealth.com/contactus.


References:

  1. http://www.obroncology.com/obrgreen/article/Whats-in-Store-at-ASCO-2014#_ftn3
  2. Heinemann, Abstract LBA3506, ASCO 2013.
  3. Kantar Health CancerMPact® Biomarker Analysis 2014 accessed June 11, 2014
  4. Kantar Health CancerMPact® Patient Metrics 2014 accessed June 11, 2014
  5. Kantar Health Oncology Market Access™ 2014 oncologist survey
  6. Blood First Edition Paper, prepublished online April 25, 2013; DOI 10.1182/blood-2013-03-490003
  7. IHS Global Insight: Country & Industry Forecasting, PharmaOnline International, accessed
    June 13, 2014
  8. http://online.wsj.com/news/articles/SB10001424052702303289904579196064064198886
    June 13, 2014
  9. Kantar Health Oncology Market Access™ 2013 Payer Mix Analysis

 

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