The introduction of the anti-CD20 monoclonal antibody (MAb) rituximab (Roche/Genentech/Chugai Seiyaku/Zenyaku Kogyo’s Rituxan/MabThera) profoundly revolutionized the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Although the MAbs alemtuzumab (Sanofi/Genzyme’s Campath/MabCampath) and ofatumumab (GlaxoSmithKline/Genmab’s Arzerra) have expanded treatment options for relapsed/refractory (R/R) CLL/SLL, this heterogenic patient population remains difficult to treat. The February 2014 approval of ibrutinib (Johnson & Johnson/Janssen/Pharmacyclics’ Imbruvica) represents a significant milestone in the treatment of R/R CLL and will serve to increase competition in the market. Nevertheless, significant clinical and commercial opportunity remains for therapies that can provide survival benefits greater than those of current standards of care.
Questions Answered in This Report:
- Improving overall survival and delaying disease progression are key goals in the treatment of R/R CLL/SLL (i.e., second and subsequent lines of therapy). What are the key primary and secondary clinical trial end points with which new therapies are evaluated? How do U.S. and European hematological oncologists weight specific efficacy end points and other drug attributes in their prescribing decisions for R/R CLL/SLL?
- Fludarabine + cyclophosphamide + rituximab (the FCR regimen) was the 2012 major-market sales leader for R/R CLL/SLL. What weaknesses in its profile would allow emerging therapies to gain traction in the market? Have emerging therapies demonstrated strengths on the attributes that surveyed hematological oncologists indicate are most important in their prescribing decisions? Which emerging therapies will offer the clinical improvements over currently available therapies that surveyed MCO PDs seek from new therapies?
- Overall survival and progression-free survival are key drivers of physicians’ prescribing decisions and/or are the focus of drug development for new R/R CLL/SLL therapies. What trade-offs across these and other clinical attributes are U.S. hematological oncologists willing to make when considering the use of emerging therapies for the treatment of R/R CLL/SLL? Based on the trade-offs in price and performance across key drug attributes that U.S. hematological oncologists are willing to make, how do physician preference and prescribing likelihood vary across different target product profiles for R/R CLL/SLL?
- By 2017, ibrutinib in combination with BR (bendamustine + rituximab) will emerge as the gold-standard therapy in our Drug Comparator Model because of its superior clinical profile over the key current therapies we evaluated. On what clinical attributes is ibrutinib + BR most differentiated from its competitors? Which current therapies are at greatest risk of being replaced by ibrutinib + BR?
Attributes included in conjoint analysis based assessment of target product profiles for R/R CLL/SLL:
- Median overall survival.
- Median progression-free survival.
- Overall response rate.
- Rate of grade ≥ 3 neutropenia.
- Rate of grade ≥ 3 tumor lysis syndrome.
- Rate of grade ≥ 3 infection.
- Price per 28-day cycle.
Attributes included in assessment of U.S. payers’ receptivity to new therapies for R/R CLL/SLL:
- Improved effect on progression-free survival.
- Improved overall response rate.
- Lower incidence of grade ≥ 3 neutropenia.
- Lower incidence of infections.
Physicians surveyed: 62 U.S. and 31 European hematological oncologists.
Payers surveyed: 20 U.S. MCO PDs.
Comprehensive List of Therapies Included in Our Research and Modeling:
- Fludarabine (Genzyme’s Fludara, Bayer HealthCare’s Fludara/Beneflur, generics) + cyclophosphamide (Bristol-Myers Squibb’s Cytoxan, Pfizer’s Cyclophospham, generics) + rituximab (Roche/Genentech/Chugai Seiyaku/Zenyaku Kogyo’s Rituxan/MabThera) [FCR]
- Bendamustine (Teva Pharmaceutical Industries’ Treanda, Mundipharma’s Ribomustin/Levact, Symbio Pharmaceuticals/Eisai’s Treakisym + rituximab [BR]
- Alemtuzumab (Sanofi/Genzyme’s Campath/MabCampath)
- Ofatumumab (GlaxoSmithKline/Genmab’s Arzerra)
- Chlorambucil (Aspen’s Leukeran, Techni-Pharma’s Chloraminophène) + rituximab
- Ibrutinib (Johnson & Johnson/Janssen/Pharmacyclics’ Imbruvica) + BR
- Idelalisib (Gilead Sciences) + BR
- Lenalidomide (Celgene’s Revlimid) + rituximab
- Obinutuzumab (Roche/Genentech/Chugai Seiyaku/Glycart’s Gazyva) + FC
Venetoclax (Roche/Genentech/AbbVie’s ABT-199) + rituximab