As previously mentioned, the ‘Clinical Trial Result of the Year’ CARE Award, award will recognize a group for their exceptional contribution to an area with unmet medical need. In part 1 of this blog series, I showcased a couple notable results from 2016 for drugs that have not yet been approved by the FDA. For part 2, I reviewed post conference reports released in 2016 by Biomedtracker and Datamonitor Healthcare to identify for already approved and marketed drugs in their primary indication. Two events made significant highlights at a major healthcare conference: Victoza for type 2 diabetes (T2D) and Keytruda for first-line non-small cell lung cancer (NSCLC). Results for both were high impact events that will shape treatment paradigms and substantially better patient lives.
Victoza reduced cardiovascular events associated with high-risk type 2 diabetes, including death
Results from the LEADER (ClinicalTrials.gov identifier: NCT01179048) study, which followed over 9340 people with T2D from 32 countries for 3.5–5 years, were the headline event at the American Diabetes Association (ADA) Conference and were simultaneously published in the New England Journal of Medicine in June 2016 .
The LEADER study was a Phase III international, placebo-controlled trial designed to determine the effect of Victoza on cardiovascular (CV) events. The study results show that Victoza (1.2 mg or 1.8 mg) significantly reduced the risk of the composite primary endpoint of cardiovascular (CV) death, non-fatal myocardial infarction (heart attack) or non-fatal stroke by 13% vs placebo (p=0.01), when added to standard of care in adults with T2D .
Novo Nordisk first announced in March 2016 that the trial had met the primary endpoint of showing non-inferiority as well as demonstrating superiority, with a statistically significant reduction in cardiovascular risk . Victoza became the first glucagon-like peptide-1 (GLP-1) agonist and the second diabetes drug to show a benefit on CV outcomes. In 2015, Boehringer’s Jardiance, a sodium-glucose transporter-2 (SGLT-2) inhibitor, became the first therapy to demonstrate reductions in heart failure and CV-related death in a dedicated CV outcomes trial (CVOT) in T2D patients at high risk or with a history of CV events . The data was received as breakthrough by analysts and investors in the market because there are several types of comorbidities associated with people who have diabetes. The American Heart Association reported in November 2016 that at least 68% of people age 65 or older with diabetes die from some form of heart disease .
The important LEADER study results reinforce the idea that these new class of drugs entering the market should have stronger characteristics beyond the capacity to lower glucose in the body. The positive CV outcome results from Jardiance and Victoza will begin to change the T2D treatment paradigm, providing physicians with a clearer choice of treatment options in second and third line, after metformin use. The relationship between increasing prevalence rates for obesity and T2D is forecast to lead to an increased need for weight-reducing therapies, and Datamonitor Healthcare forecast that both the GLP-1 agonist and SGLT-2 inhibitor classes will benefit the most from this trend .
Keytruda monotherapy reduced the risk of disease progression or death in first-line non-small cell lung cancer
Merck & Co. experienced a successful year in 2016 as the company disrupted the NSCLC market with its groundbreaking KEYNOTE-024 (ClinicalTrials.gov identifier: NCT02142738) study, where Keytruda was shown to be superior to chemotherapy in the first-line setting. The KEYNOTE-024 study was a pivotal Phase III trial evaluating Keytruda monotherapy compared to standard of care (SOC) platinum-based chemotherapies in the treatment of patients with advanced NSCLC. Additionally, patients enrolled were required to have no prior systemic chemotherapy treatment for their advanced disease and tumors which expressed high levels of PD-L1 (defined as a tumor proportion score of 50% or more).
Preliminary results of the KEYNOTE-024 study were presented in June 2016 and Merck announced that Keytruda was superior compared to chemotherapy for both the primary endpoint of progression-free survival (PFS) and the secondary endpoint of overall survival (OS) . In October 2016, quantitative results were presented at the European Society for Medical Oncology (ESMO) conference and the data showed Keytruda reduced the risk of disease progression or death by 50% and the risk of death by 40% against chemotherapy among patients expressing PD-L1 levels of 50% or higher . Chemotherapy has been the foundation of first-line NSCLC treatment for decades and the high incidence and poor clinical outcomes continue to make lung cancer the most common cause of cancer-related mortality worldwide .
Keytruda’s trial design will inform future studies in NSCLC and other oncology indications, as companies work to identify patients who will benefit best from a specific therapy and the positive results are set to change the treatment paradigm. These results helped solidify PD-1 checkpoint inhibitors in the NSCLC treatment paradigm and thought leaders at the conference described the data as “transformational” . Within the same month, the FDA approved Keytruda for the first-line treatment of patients with metastatic NSCLC whose tumors have high PD-L1 expression (tumor proportion score [TPS] of 50 percent or more) .
Beyond its commercial potential and impact on extending patient lives, what makes this study so remarkable is that it’s main competitor Bristol-Myers Squibb (BMS) ran a similar study with Opdivo in first-line and had negative results. BMS was poised to have Opdivo be the standard of care for first-line lung cancer patients, but results from the CheckMate 026 study presented at ESMO showed no evidence for efficacy and found that it fared worse than its chemotherapy comparator. This immediately prompted discussion among analysts and thought leaders that the failure of the Checkmate 026 study could have been the result of a poorly designed clinical trial, where the company aimed for too low of a threshold for PD-L1 expression .
The clinical contribution by Novo Nordisk and Merck are creating a new baseline in how future therapies for patients with diabetes or lung cancer will be developed. The positive results reported with Victoza provide hope for patients living with comorbidities associated with diabetes and results of Keytruda for patients with lung cancer are a major step forward in the effort to save and prolong patient life in this hard to treat cancer.
For more information about the Clinical and Research Excellence (CARE) Awards, including how to book a table or sponsorship opportunities, please visit clinicalresearchexcellence.com
 Biomedtracker, Datamonitor Healthcare (2016) Biomedtracker / Datamonitor Post-ADA Report.
 Novo Nordisk (2016) Victoza® (liraglutide) significantly reduced the risk of major cardiovascular events and death in adults with type 2 diabetes in the LEADER trial.
 Novo Nordisk (2016) Victoza significantly reduces the risk of major adverse cardiovascular events in the LEADER trial.
 Eli Lilly (2015) Jardiance® (empagliflozin) is the only diabetes medication to show a significant reduction in both cardiovascular risk and cardiovascular death in a dedicated outcome trial.
 American Heart Association (2016) Cardiovascular Disease & Diabetes.
 Datamonitor Healthcare (2016) Forecast: Type 2 Diabetes in the US, Japan, and 5EU.
 Merck (2016) Merck’s KEYTRUDA® (pembrolizumab) Demonstrates Superior Progression-Free and Overall Survival Compared to Chemotherapy as First-Line Treatment in Patients with Advanced Non-Small Cell Lung Cancer.
 Merck (2016) Two Major Studies to Be Presented at ESMO 2016 Congress Presidential Symposium Demonstrate Potential of Merck’s KEYTRUDA® (pembrolizumab) for the First-Line Treatment of Metastatic Non-Small Cell Lung Cancer in a Broad Range of Patients.
 Datamonitor Healthcare (2016) Treatment: Non-Small Cell Lung Cancer in the US, Japan, and 5EU.
 Pharmaphorum (2017) Eye on ESMO: Day Three – Merck & Co. wins big lung cancer battle.
 Merck (2016) FDA Approves Merck’s KEYTRUDA® (pembrolizumab) in Metastatic NSCLC for First-Line Treatment of Patients Whose Tumors Have High PD-L1 Expression (Tumor Proportion Score [TPS] of 50 Percent or More) With No EGFR or ALK Genomic Tumor Aberrations.
 Pharma Intelligence (2017) The Emergence of PD-1 Immunotherapies: An Analysis Between Keytruda and Opdivo in NSCLC.