A research team, including the Food and Drug Administration (FDA) Stanford and a boutique data analysis firm called Acumen, set up a study comparing outcomes between relapsed follicular lymphoma and relapsed chronic lymphocytic leukemia patients treated with Idelalisib (IDEL) in the Medicare-covered clinic versus actual clinical trial data. This study could be categorized as using Real-World Evidence (RWE) as compared to clinical trial data to assess outcomes in the therapeutic area with idelalisib.

What is Idelalisib?

The drug is an approved monotherapy sold under the brand name Zydelig and used to treat certain blood cancers. The substance acts as a phosphoinositide 3-kinase inhibitor—it blocks  P110δ, the delta isoform of the enzyme phosphoinositide 3-kinase. Developed by Gilead Sciences, the drug had annual sales of $168 million by 2016, up from $132 million in 2015. Sales went up to $149 million in 2017 and back down to $133 million in 2018.

Note: Deaths Halt Frontline Studies

Earlier this year, deaths forced maker Gilead to halt frontline studies. The studies were testing Zydelig in newly diagnosed leukemia and lymphoma patients, part of Gilead’s attempt to expand the use of the blood cancer therapy reported FiercePharma. Now it is only designated for patients who have relapsed after previous treatment.

The Study

This cohort study compared clinical trial participants treated with IDEL, aged 65 years or older, in studies 101-09 and 312-0116 with Medicare beneficiaries treated with IDEL of the same disease state and treatment regimen. Study 101-09 was a phase 2, single-group, open-label trial supporting accelerated approval of IDEL for relapsed or refractory FL. Study 312-0116 was a phase 3, multicenter, randomized, double-blind trial supporting approval of IDEL+R for relapsed CLL. Analyses were conducted between February and December 2018.

The team compared treatment duration, on-treatment, overall mortality, and seriously fatal interactions between trial participants and Medicare beneficiaries. The team used Cox proportional hazards models quantified differences by cohort.

The Results

As reported by JAMA Oncology, they identified 26 trial participants and 305 Medicare beneficiaries with comparable means, age, gender, etc. (see link for details). The research team observed “substantial imbalances in baseline comorbidities and treatment outcomes between Medicare beneficiaries and trial participants 65 years or older. Immunosuppression-related toxic effects, including infections, may have been somewhat reduced in trials by more frequent dose reductions and exclusion of patients with ongoing infections. Selective eligibility criteria and closer monitoring of trial participants may be responsible for limited generalizability of trial data to clinical practice.”

Research Team

The research team included the Food and Drug Administration (Office of Pharmacovigilance and Epidemiology; Office of Hematology and Oncology Products, Division of Hematology Products; Division of Biometrics, Office of Biostatistics) as well as Stanford University Department of Economics, US Health and Human Services Centers for Medicare & Medicaid Services and Acumen, LLC.

Lead Research/Investigators

Steven T. Bird, PhD, PharmD, MS, Office of Pharmacovigilance and Epidemiology, Food and Drug Administration, Silver Spring, Maryland

Fang Tian, PhD, MHS, MPH, Office of Pharmacovigilance and Epidemiology, Food and Drug Administration, Silver Spring, Maryland

Natasha Flowers, BA, Acumen LLC, Burlingame, California

Donna Przepiorka, MD, PhD, Office of Hematology and Oncology Products, Division of Hematology Products, Food and Drug Administration, Silver Spring, Maryland

Rongrong Wang, MPH Acumen LLC, Burlingame, California

Tae-Hyun Jung,  PhD, Division of Biometrics, Office of Biostatistics, Food and Drug Administration, Silver Spring, Maryland

Zebulin Kessler, BS, Acumen LLC, Burlingame, California

Corrine Woods, RPH, MPH, Office of Pharmacovigilance and Epidemiology, Food and Drug Administration, Silver Spring, Maryland

Bo Kim, BA, Acumen LLC, Burlingame, California

Barry W. Miller, MS, CRNP, Office of Hematology and Oncology Products, Division of Hematology Products, Food and Drug Administration, Silver Spring, Maryland

Michael Wernecke, BA, Acumen LLC, Burlingame, California

Clara Kim, PhD, Division of Biometrics, Office of Biostatistics, Food and Drug Administration, Silver Spring, Maryland

Stephen McKean,PhD, Acumen LLC, Burlingame, California

Kate Gelperin, MD, MPH, Office of Pharmacovigilance and Epidemiology, Food and Drug Administration, Silver Spring, Maryland

Thomas E. MaCurdy, PhD, Department of Economics, Stanford University, Stanford, California; Acumen LLC, Burlingame, California

Jefferey Kelman, MD, Centers for Medicare & Medicaid Services, Woodlawn, Maryland

David J. Graham, MD, MPH, Office of Pharmacovigilance and Epidemiology, Food and Drug Administration, Silver Spring, Maryland

Source: JAMA Oncology

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