The OBR Blog

July 30, 2015 - 11:07 am Posted in Featured comments0 Comments

Introduction

OBR and MDoutlook are pleased to share excerpts from the most recent MDoutlook’s OncoPolls™ from this year’s ASCO and EHA annual meetings. This report highlights certain presentations concerning the treatment of Chronic Lymphocytic Leukemia (CLL) and Multiple Myeloma (MM). This research is based on separate surveys conducted for each hematologic malignancy. The full complimentary report is available through MDoutlook per details below.

OncoPoll™ Methodology

  • Primary research phase involved global surveys to verified and validated hematologic and medical oncologists with an identified clinical interest in hematologic malignancies utilizing targeting parameters within the proprietary MDoutlook® global cancer treater panel
  • Timing: July 2015. Launched shortly after close of 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago, IL., May 29-June 2, 2015 and the 20th Congress of European Hematology Association (EHA), held in Vienna, Austria, June 11-June 14, 2015
  • Fielding via interactive web-based survey instruments, utilizing proven MDoutlook methodology and proprietary technology
  • Links to discussed abstracts on the ASCO and EHA websites were provided within the survey
  • Responses: 79 global physicians in CLL survey and 75 global physicians in multiple myeloma survey

Impact of ASCO/EHA Presentations on Ibrutinib Usage in CLL

Key Conclusions

  • Ibrutinib usage in fludarabine refractory and relapsed CLL will increase from ~1/4 of patients to over 1/3 of patients
    • Usage in fludarabine refractory patients expected to see a 77% increase
    • 58% increase in usage is expected for relapsed CLL
  • In the 1st line setting, ibrutinib usage will also increase, dependent on the patient subtype
  • Overall, the clinical importance of the presentations of the HELIOS clinical trial was rated as 4.25 on a 1-5 scale (data not shown)

Impact of ASCO/EHA Presentations on Usage of anti-CD20 Antibodies in CLL

Key Conclusions

  • Based on the presentations at ASCO & EHA (Complement 2 trial), physicians expect to double their usage of obinutuzumab and ofatumumab in CLL
    • Rituximab will remain the dominant choice, with only an absolute loss of ~5% of CLL patients receiving it
  • Overall, the clinical importance of the Complement 2 presentations was rated as 3.54 on a 1-5 scale (data not shown)

Awareness and Expected Impact of Selected New Agents for CLL

Key Conclusions

  • 87-88% of physicians have at least some awareness about the bcl-2 inhibitor venetoclax and the PI3K inhibitors duvelisib and TGR-1202
  • Physicians have a very positive outlook for venetoclax, with over 40% expecting this agent to have a large impact on many CLL patients
  • Both new PI3K inhibitors are also positively viewed, albeit slightly less positive than the bcl-2 inhibitor
    • Little to no differences are currently seen between duvelisib and TGR-1202

Expected Usage of Elotuzumab Today in Relapsed / Refractory Myeloma, if Commercially Available

Key Conclusions

  • Overall, respondents would use elotuzumab in 58% of their MM patients with refractory disease and 52% of their relapsed MM patients
  • Based on current presentations, ALL respondents would use it in at least some of their MM patients
  • ~40% of physicians would treat most (>60%) of their relapsed / refractory MM patients with elotuzumab

Expected Impact of Daratumumab for the Treatment of Relapsed Multiple Myeloma

Key Conclusions

  • Overall impact rated as 5.4 (1 to 7-point scale)
  • 81% of the respondents rate daratumumab as 5 or higher
    • Nobody rates its impact as “Little or none” (1)

Treatment of Relapsed MM: Kd Expected to Surpass Vd

Key Conclusions

  • Kd (carfilzomib + dexamethasone) expected to show >50% relative increase in usage in relapsed multiple myeloma, to 38% of patients
  • Expected usage of Vd (bortezomib + dexamethasone) will decrease by ~20% to 1/3 of patients

Conclusions: Immediate Impact of 2015 ASCO & EHA Presentations on Clinical Practice for CLL & MM

CLL

  • Both the HELIOS and Complement 2 clinical trials will impact the CLL treatment landscape
    • Ibrutinib usage is expected to rise by 50% to 110% across all CLL subgroups in the next 6 months
    • Anti-CD20 mAb usage in CLL is slowly shifting from 1st generation rituximab to 2nd / 3rd generation ofatuzumab and obinutuzumab
  • Physicians have very high expectations for the BCL-2 Inhibitor venetoclax in CLL
    • The new PI3K inhibitors duvelisib and TGR-1202 are also positively viewed

Multiple Myeloma

  • The immune-oncology revolution has come to multiple myeloma with 2 new monoclonal antibodies: the anti-CS1 mAb elotuzumab and the anti-CD38 mAb daratumumab
  • Virtually all oncologists would use elotuzumab in at least some of their relapsed / refractory myeloma patients if it were commercially available today
    • 40% of respondents reported they would use it in 60% or more of their patients
    • Overall, ~50-60% of relapsed / refractory myeloma patients would receive it as treatment
  • Carfilzomib (Kd) is expected to become the preferred proteasome inhibitor over bortezomib (Vd) in the therapy of relapsed MM

For a more detailed analysis report, please click here to download the full report.

Submitted by Robert Stephan, Sr. Director Medical Services and Strategy, and Jan Heybroek, President MDoutlook.

July 20, 2015 - 09:07 am Posted in Featured comments0 Comments

In 2016, the National Institute of Health (NIH) will be introducing the Precision Medicine Initiative, a program designed to better understand the role that individual differences play in health, with a goal of developing better prevention and treatment strategies tailored to the individual.1 The government’s $215 million investment in precision medicine includes $70 million to the National Cancer Institute (NCI) to scale up efforts to identify genomic drivers in cancer and apply that knowledge in the development of more effective approaches to cancer treatment.2 Clearly, the path toward precision medicine and molecular diagnostics is set, and manufacturers, physicians, and payers alike will need to develop their understanding of the challenges and promises they bring.

For insight into how molecular diagnostics is reshaping oncology treatment, Encuity Research surveyed oncologists immediately after last month’s meeting of the American Society of Clinical Oncology (ASCO). Encuity received responses from more than 100 clinicians engaged in direct patient care, and the results suggest that oncologists fully anticipate the increasing adoption of molecular diagnostics over the next decade.

Three-quarters of the oncologists surveyed report a high level of familiarity with molecular diagnostics in the cancer marketplace. Thirty-one percent of physicians report that they were exposed to themes concerning molecular diagnostics at ASCO, with the biggest focus on personalized treatment and future use.

The rise of molecular diagnostics goes against the trend toward treatment pathways over the last decade. For physicians, treatment pathways were appreciated because they offered a certain level of predictability in terms of outcomes. Payers liked them because they helped with budgeting for the next year. Now, however, the use of molecular diagnostics will shift the trend away from grouping patients into certain treatment pathways toward the less structured terrain of personalized medicine.

Molecular diagnostics requires physicians to look at the patient individually to understand the nuances of the disease—nuances traditional diagnosis methods would not have captured. This may necessitate a change to the treatment paradigm in which treatment pathways tree out into multiple different branches. This is an overarching problem in the market today, and the question faced by physicians is, “Do I trust the new molecular diagnostic test or do I trust the existing standard protocol?”

More than half of oncologists Encuity surveyed report that they would be likely to use molecular diagnostics for patients who lack other therapy options. But in cases where patients had options, only 24% of oncologists said they’d use the new diagnostic tools. In the same way, physicians are more likely to try the new immunotherapies on patients who have failed to respond to traditional first-line therapies. Doctors report that robust clinical trials with defined outcomes would have the biggest impact on their future use of molecular diagnostics.

Numerous types of tests fall under the label of molecular diagnostics. Among the most interesting are comprehensive genomic testing, circulating tumor cell tests, and cell-free DNA technology.

Comprehensive genomic testing uses a single test to provide physicians with a broad view of the targeted treatment options available by detecting all types of alterations, in all the regions where they can occur, for all the genes that are known to be associated with cancer.3

Cell-free DNA technology and circulating tumor cell technology are genomic tests that do not require a biopsy as in standard genomic testing. Rather than surgically removing tissue from the patient using a needle puncture, cell-free DNA technology and circulating tumor cell technology are diagnostics cased on a blood draw. Because blood sampling can be performed more often, such tests can be used as a diagnostic tool and for monitoring patient progress.

The vast majority of physicians surveyed are aware of both comprehensive genomic testing (92%) and circulating tumor cell tests (89%), while only 57% of respondents indicated they are aware of cell-free DNA technology. Asked to indicate their level of excitement with regard to the potential impact of these tests on cancer diagnosis and treatment on a scale of 1 (Not At All Excited) to 7 (Extremely Excited), comprehensive genomic tests and cell-free DNA technology received a rating of 5.5, while circulating tumor cell tests received a ranking of 4.7.

When asked to look out over the next 10 years, oncologists say they expect to see their use of comprehensive genomic testing increase to nearly half their patients, while they anticipate that emerging molecular diagnostic tests will account for one-quarter of their treatment decisions.

Encuity Research is the marketing research group within Campbell Alliance/inVentiv Health Consulting. For a full version of Encuity’s ASCO Impact Report, please visit http://www.encuity.com/asco.

By Dave Johnson, Vice President, Encuity Research

1 The National Institute of Health. Precision Medicine Initiative. Available at http://www.nih.gov/precisionmedicine/. Accessed 6/25/2015.

2 The White House. FACT SHEET: President Obama’s Precision Medicine Initiative. Available at https://www.whitehouse.gov/the-press-office/2015/01/30/fact-sheet-president-obama-s-precision-medicine-initiative. Accessed 6/25/2015.

3 Foundation Medicine. Comprehensive Genomic Profiling May Offer More Treatment Options to Patients with Lung Cancer. Available at http://www.foundationmedicine.com/2015/01/comprehensive-genomic-profiling-may-offer-more-treatment-options-to-patients-with-lung-cancer/. Accessed 6/25/2015.

July 09, 2015 - 07:07 am Posted in Featured comments0 Comments

Introduction

OBR and MDoutlook are pleased to share excerpts from the most recent MDoutlook’s OncoPolls™ from ASCO 2015. This report highlights certain presentations concerning the anti-PD-1 / PD-L1 antibody-based Immune Checkpoint Inhibitors and other new agents in Gastrointestinal cancers. This research is based on separate surveys in non-Colorectal Gastrointestinal cancer and Colorectal cancer. The full complimentary report is available through MDoutlook per details below.

OncoPoll™ Methodology

  • Primary research phase involved global surveys to verified and validated medical oncologists and multi-disciplinary physicians with an identified clinical interest in GI cancers utilizing targeting parameters within the proprietary MDoutlook® global cancer treater panel
  • Timing: June 2015. Launched shortly after close of 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago, IL., May 29-June 2, 2015
  • Fielding via interactive web-based survey instrument, utilizing proven MDoutlook methodology and proprietary technology
  • Links to discussed abstracts on the ASCO website were provided within the survey
  • Responses: 86 global physicians in non-CRC GI Cancer survey and 82 US physicians in CRC survey

Expected Impact of Immune Checkpoint Blockade Antibodies in Non-CRC GI Cancer

Key Conclusions

  • Anti-PD-1 / PD-L1 antibodies are mainly expected to have a large impact for small patient groups
    • 27% of the respondents expect large patient collectives to be impacted
    • Only 2% of the respondents expect no impact at all
  • Impact on therapy was estimated marginally higher for Gastric compared to Esophageal and HCC

Perceived Value of Immune Checkpoint Blockade Antibodies in Non-CRC GI Cancer

Key Conclusions

  • Overall calculated average of 4.05 (for comparison: NSCLC 4.74 [data: 2015 OncoPoll NSCLC])
  • 15% of physicians perceive the value of these antibodies, at current prices, as being high / very high (for comparison: NSCLC 27% [data: 2015 OncoPoll NSCLC])
  • Two thirds (67%) perceive the value in the medium range (3-5 on a 7-point scale)


Multi-Factorial Impact of Targeted Agents as a Therapeutic Strategy for BRAF-Mutated mCRC

Key Conclusions

  • The therapeutic strategy of combining BRAF (+/-MEK) inhibition with EGFR inhibitors is seen to have limited potential for BRAF-mutated mCRC
  • Nearly half of physicians think this approach will have only small impact on a selected few number of these patients
    • A third of respondents think the clinical impact will be larger, but still restricted in the patient subset benefiting from this approach

Perceived Value of Immune Checkpoint Blockade Antibodies in mCRC

Key Conclusions

  • Overall calculated average of 4.56
    • Compares with average of 4.74 seen in NSCLC [data: 2015 OncoPoll NSCLC]
  • Over ¼ of physicians (27%) perceive the value of these antibodies, at current prices, as being high / very high


Expected Impact of PEGH20 on Pancreatic Cancer Treatment Landscape

Expected Clinical Impact of PEGH20

Key Conclusions

  • Overall impact rated as 5.56 (1 to 10-point scale)
  • 75% of the respondents expect PEGH20 to make intermediate or high clinical impact


Regorafenib in Advanced Gastric and Gastric Esophageal Junction Cancer: Expected to be Widely Used

Expected use of regorafenib in advanced G/GEJ cancer

Key Conclusions

  • Main usage of regorafenib is expected to be in 3rd and 4th lines of therapy
  • 99% of physicians would use regorafenib in G/GEJ cancers if granted regulatory approval (data not shown)
  • 80% of the respondents expect to use regorafenib in 2 or more lines (data not shown)

Impact of Abstract# LBA100: Expected Usage of Testing for MMR Deficiency and Treatment with Immune Checkpoint Blockade Antibodies in MMR-Deficient mCRC

Key Conclusions

  • Physicians expect to test two-thirds of their mCRC patients for mismatch repair (MMR) deficiency over the next 6 months; 45% growth from current levels
    • Almost half of physicians (47%) will test all of their mCRC patients for MMR deficiency (data not shown)
  • Treatment of MMR-deficient mCRC with anti-PD-1/PD-L1 antibodies is expected to nearly double (182%) over the next 6 months
    • 28% of this patient subset is expected to receive this therapeutic approach

Conclusions: Immediate Impact of 2015 ASCO Presentations on Clinical Practice

Non-CRC GI Cancers

  • Anti-PD-1/PD-L1 antibodies are expected to have a large impact for selected patients with Gastric, Esophageal and Hepatocellular Cancers
  • At current drug costs, only average value is placed on these agents in GI cancers (lower than what is seen for NSCLC)
  • 75% of the respondents expect the PEGH20 addition to have intermediate or high clinical impact on the treatment of pancreatic cancer
  • Regorafenib will be widely used in advanced G/GEJ cancers upon regulatory approval

Metastatic Colorectal Cancer

  • The immune checkpoint inhibitors (anti-PD-1/PD-L1) are going to have a very significant impact on the treatment landscape for MMR-deficient mCRC
    • Over a quarter of mCRC patients with this deficiency are expected to receive this treatment almost immediately
    • Most mCRC patients will now be tested for an MMR deficiency
  • At today’s prices, physicians see good value in using the anti-PD-1/PD-L1 antibodies for mCRC
  • Combining BRAF+/-MEK inhibitors with anti-EGFR antibodies is initially seen to have only a limited impact on the treatment of BRAF-mutated CRC

For a more detailed analysis report, please click here to download the full report.

Submitted by Robert Stephan, Sr. Director Medical Services and Strategy, and Jan Heybroek, President MDoutlook.

July 06, 2015 - 10:07 am Posted in Featured comments0 Comments

By: Debbie Warner, Vice President, Oncology Commercial Strategies, Kantar Health

Value was an overarching theme at ASCO 2015 and has been a topic of ongoing focus, as have been the burgeoning pipeline of immunotherapy agents, with the recently launched PD-1 inhibitors, Opdivo® (nivolumab, Bristol Myers Squibb) and Keytruda® (pembrolizumab, Merck), being the highlights of ASCO 2015. Presenter Leonard Saltz, M.D. of Memorial Sloan Kettering praised the clinical value of an Opdivo + Keytruda combination as being “truly, truly remarkable,” but he added that with the combination costing nearly $300,000 (if continued for 11 months) “these drugs cost too much –unsustainable.” While Dr. Saltz is an unabashed critic of cancer drug prices, $300,000 would give most people pause. Concern about the increasing cost of breakthrough cancer treatment heightens when one considers the number of immunotherapies – like Opdivo and Keytruda – in development for a broad range of solid tumors as well as hematologic malignancies. In fact, at least 33 of the 279 trials studying immune therapies are for combinations with each other and/or in combination with other novel agents. Cost of novel therapy combinations may be the most important factor in limiting these treatments moving forward, and it’s no surprise that discussions of the game-changing nature of immunotherapy are often accompanied by questions of cost sustainability.

While the easiest way to address the issue of cost may be to dramatically cut prices, development and innovation would no longer flourish. A more realistic approach would be to limit treatment to those patients most likely to respond, as assessed by some objective biomarker. Payers and providers would agree that this makes sense in principle. After all, retrospective analyses of data from clinical trials have shown positive correlations between PD-L1 expression and efficacy. However, researchers are unanimous that there is too much scientific evidence that PD-L1 expression is not an appropriate biomarker for it to be used for patient selection. Further, payers seem unconvinced that biomarkers are the solution. In an April 2015 Kantar Health Oncology Market Access survey, 86 commercial payers expressed tepid enthusiasm about the value of biomarkers.

Further, only about 30% of payers require submission of a positive biomarker test before approving utilization of drugs with biomarker status specified in their label.

In the same survey, however, nearly half of payers identified NSCLC and malignant melanoma as the top targets for utilization management. So what are the alternatives?

Clinical pathways in oncology have garnered tremendous attention over the last few years as a useful tool in improving the value derived from cancer treatment. Though only 20% of payers surveyed identified pathways as the measure most likely to succeed in slowing the growth of treatment costs, 37% indicated that they currently have pathway programs in place. Similarly, 37% of the 150 community oncologists participating in Kantar Health’s Oncology Market Access research indicated that they participate in pathway programs.

While it is unlikely that payers will absolutely deny coverage of these drugs when they are clinically appropriate, their definition of clinically appropriate is increasingly likely to take into consideration performance status, line of therapy, specific prior therapies and potentially PD-L1 expression.

Recognizing that they may be fighting an uphill battle in their efforts to strictly manage the utilization of immunotherapies, payers could rely on novel reimbursement approaches that shift reimbursement away from buy-and-bill and toward models that include financial accountability for oncologists. Models such as episode of care reimbursement, accountable care organizations and drug carve-outs can limit payers’ exposure to drug costs while leaving to oncologists’ clinical and fiscal judgment which treatment approach makes the most sense for any particular patient.

Finally, value-based approaches are being developed, such as ASCO’s Value in Oncology and McKesson’s Value Pathways, powered by NCCN. However, payers are skeptical that simply developing a rating system will have any impact on utilization, especially in the absence of financial risk for oncologists, patients and/or manufacturers.

That leaves the question of “Where is the breaking point?” That point can only be known after it has passed; presumably no stakeholder wishes to get there. Enter the concept of performance-based pricing. Not a new concept (it is commonly employed in several European countries) it has received significant media attention, most notably calls from Express Scripts to price a drug differentially by indication depending on its efficacy.

The concept of pricing based on efficacy in an indication or providing rebates on a patient-by-patient basis has merit but will be difficult implement due to an array of challenges, one of which would literally take an act of Congress to close. These challenges include:

  • Arriving at a consensus on the definition of efficacy
  • Siloed budgets between the medical benefit and the pharmacy benefit
  • Ability to capture the necessary data
  • Need for manufacturers to recoup amortized development costs
  • Expected Wall Street reaction to cut in net price
  • Likelihood that payers will “undervalue” even dramatic benefit
  • Government pricing that would at best result in minimal price for all of the drug paid by these programs and at worst severe penalties

A prospective approach would be ideal but would rely on the ability to limit treatment to patients who will benefit. Unfortunately, science is not there yet for immunotherapy. If and when researchers find an appropriate biomarker, confidence in the reliability of the test will remain a critical issue. Given the potential curative nature of immunotherapy, what level of false negatives will physicians and patients tolerate? This is yet another example of technology outpacing policy.  The question is, when and how will payers and policy-makers catch up?

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