Clarion Blog

Oncology drug development continues at an unprecedented pace—our experts examine recent trends and detail what to expect this year:

• The first immunotherapy + targeted therapy combinations on the verge of launch
  • Immune checkpoint inhibitors have received over 40 FDA approvals already, but thus far all approvals have been for IO monotherapy or for IO+IO or IO+chemotherapy combinations¹. 2019 may see the first approval(s) of an anti-PD1/PD-L1 agent combined with kinase-targeted therapy; such combinations have shown excellent data at major conferences in the past couple of years^2,3,4

• The next IO+IO combination breakthrough may emerge
  • Thus far the only approved IO+IO regimen remains nivolumab + ipilimumab (BMS)¹, and dozens of clinical trials for other combinations have failed^2,3. However, hundreds more trials for novel IO+IO combinations are underway⁴, some with promising early data^2–5. Data readouts this year will build on early signals and also include many more shots on goal on enhancing anti-PD1 efficacy, increasing I-O biomarker precision, addressing anti-PD1 failure, and turning “cold” tumors “hot”. Success on any of these fronts would be a leap forward in immunotherapy

• The next wave of CAR-T therapies will continue to progress
  • The CAR-T era began in 2017 with FDA approvals of CD19-targeted CAR-T therapies Kymriah (Novartis) and Yescarta (Gilead/Kite)¹. In 2019, we will see new data readouts and new trials for CAR-T therapies that target new antigens (e.g., BCMA), express new transgenes (e.g., armored T cells), target solid tumors, treat autoimmunity (e.g., CAR-Treg therapy), or work as off-the-shelf treatments^2–7

• Precision oncology will continue to expand
  • Continued approvals for new targeted therapy mechanisms are expected, including those directed against biomarker-defined subgroups of patients^2–7. These approvals will increase the clinical utility of multigene next-generation sequencing (NGS) tests, and thus will be a driving force in the growing use of NGS. Current barriers to NGS multigene testing include limited coverage among commercial payers, long turnaround times, and data complexity. The expansion of NGS use will increase motivation to lower those barriers and drive further innovation in targeted therapy—potentially resulting in a positive feedback loop driving the precision oncology paradigm

• Cost containment in oncology will become more stringent
  • The rise in cost of cancer care—and of healthcare more broadly—is unsustainable, especially in the US³, and mechanisms to control costs are already in motion. For example, under MACRA, CMS has already begun a process of payment reform through the Merit-based Incentive Payment System (MIPS) and Alternative Payment Models (APMs). In 2019, MIPS will double its performance threshold, and a subset of APMs may become mandatory^8,9, thus shifting the incentives and financial risks for oncology practices.
  • Furthermore, the nation is on the verge of drug pricing reform. The White House, the new Congress, and the Senate have all signaled a commitment to regulate drug pricing. This is in addition to the numerous state-level approaches being advanced. Many approaches are on the table, including a radical proposal from Health and Human Services (HHS) to establish an International Pricing Index (IPI) for Medicare Part B drugs and abolish the buy-and-bill model¹⁰. If approved, this would occur in a multi-stage process over several years, but the ultimate impact could be enormous. On average, Medicare Part B drugs are priced ~80% higher in the US than other developed countries¹⁰. Thus a sizable percentage of pharma annual revenue could be eliminated by the IPI and/or other pricing reforms.

Sources: 1) FDA; 2) AACR; 3) ASCO; 4) ESMO; 5) ASH; 6) ClinicalTrials.gov; 7) Company press releases; 8) CMS; 9) AJMC; 10) HHS

Oncology drug development continues at an unprecedented pace—our experts examine recent trends and detail what to expect this year:

• The first immunotherapy + targeted therapy combinations on the verge of launch
  • Immune checkpoint inhibitors have received over 40 FDA approvals already, but thus far all approvals have been for IO monotherapy or for IO+IO or IO+chemotherapy combinations¹. 2019 may see the first approval(s) of an anti-PD1/PD-L1 agent combined with kinase-targeted therapy; such combinations have shown excellent data at major conferences in the past couple of years^2,3,4

• The next IO+IO combination breakthrough may emerge
  • Thus far the only approved IO+IO regimen remains nivolumab + ipilimumab (BMS)¹, and dozens of clinical trials for other combinations have failed^2,3. However, hundreds more trials for novel IO+IO combinations are underway⁴, some with promising early data^2–5. Data readouts this year will build on early signals and also include many more shots on goal on enhancing anti-PD1 efficacy, increasing I-O biomarker precision, addressing anti-PD1 failure, and turning “cold” tumors “hot”. Success on any of these fronts would be a leap forward in immunotherapy

• The next wave of CAR-T therapies will continue to progress
  • The CAR-T era began in 2017 with FDA approvals of CD19-targeted CAR-T therapies Kymriah (Novartis) and Yescarta (Gilead/Kite)¹. In 2019, we will see new data readouts and new trials for CAR-T therapies that target new antigens (e.g., BCMA), express new transgenes (e.g., armored T cells), target solid tumors, treat autoimmunity (e.g., CAR-Treg therapy), or work as off-the-shelf treatments^2–7

• Precision oncology will continue to expand
  • Continued approvals for new targeted therapy mechanisms are expected, including those directed against biomarker-defined subgroups of patients^2–7. These approvals will increase the clinical utility of multigene next-generation sequencing (NGS) tests, and thus will be a driving force in the growing use of NGS. Current barriers to NGS multigene testing include limited coverage among commercial payers, long turnaround times, and data complexity. The expansion of NGS use will increase motivation to lower those barriers and drive further innovation in targeted therapy—potentially resulting in a positive feedback loop driving the precision oncology paradigm

• Cost containment in oncology will become more stringent
  • The rise in cost of cancer care—and of healthcare more broadly—is unsustainable, especially in the US³, and mechanisms to control costs are already in motion. For example, under MACRA, CMS has already begun a process of payment reform through the Merit-based Incentive Payment System (MIPS) and Alternative Payment Models (APMs). In 2019, MIPS will double its performance threshold, and a subset of APMs may become mandatory^8,9, thus shifting the incentives and financial risks for oncology practices.
  • Furthermore, the nation is on the verge of drug pricing reform. The White House, the new Congress, and the Senate have all signaled a commitment to regulate drug pricing. This is in addition to the numerous state-level approaches being advanced. Many approaches are on the table, including a radical proposal from Health and Human Services (HHS) to establish an International Pricing Index (IPI) for Medicare Part B drugs and abolish the buy-and-bill model¹⁰. If approved, this would occur in a multi-stage process over several years, but the ultimate impact could be enormous. On average, Medicare Part B drugs are priced ~80% higher in the US than other developed countries¹⁰. Thus a sizable percentage of pharma annual revenue could be eliminated by the IPI and/or other pricing reforms.

Sources: 1) FDA; 2) AACR; 3) ASCO; 4) ESMO; 5) ASH; 6) ClinicalTrials.gov; 7) Company press releases; 8) CMS; 9) AJMC; 10) HHS

If you are interested in learning more about Clarion’s work in oncology, please see the “Our Work” section of our website.