Clinical Therapeutic Intelligence Report: Year in Review Last year marked a productive year for oncology drug research and development with ten new oncology drugs coming to market two of which were granted accelerated approval by the FDA. In addition, seven drugs were approved with new label indications. Our 2013 Year in Review provides an overview of the oncology therapies approved over the last twelve months, as well as current trends in drug development and distribution channel strategies. We will also look ahead at ten therapies coming down the pipeline for approval in 2014. 2013 Oncology Drug Approvals 2013 marked a big year for approvals in treatment options for certain types of blood. Of note, Pharmacyclics IMBRUVICA (ibrutinib) was approved for relapsed or refractory Mantle Cell Lymphoma (MCL), and is the first in its class of oral Bruton s tyrosine kinase (BTK) inhibitors. During a single arm clinical trial, IMBRUVICA showed an overall response rate of 68%, and is the first drug to receive the FDA s Breakthrough Therapy designation. Imbruvica s approval demonstrates the FDA s commitment to making treatments available to patients with rare diseases, said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA s Center for Drug Evaluation and Research, in a statement i. The agency worked cooperatively with the companies to expedite the drug s development, review and approval, reflecting the promise of the Breakthrough Therapy Designation program. According to an article published in Pharmaceutical Executive, IMBRUVICA costs just under $11,000 per month, with an annual price tag of $132,000 for MCL patients ii. The same article mentions that should IMBRUVICA be approved for chronic lymphocytic leukemia, those patients will have a slightly lower price tag around $8,200 per month, since patients would take three pills per day as opposed to the four taken by MCL patients. postitive (Ph+) acute lymphoblastic leukemia, Iclusig was temporarily suspended from sales and marketing by the FDA on October 31, 2013. The suspension was mandated so that the FDA could further investigate the safety of the drug due to the risk of life-threatening blood clots. However, on December 20, 2013, the FDA reapproved Iclusig with a REMS program and revised indication for adult patients with refractory CML or Ph+ ALL. Iclusig has a price tag of about $125,000 per year, and is a once-daily tablet. These new therapies, which are targeted to specific mutations or patient populations, are completely changing the treatment landscape, especially for blood patients, said Ann Steagall, Director of Clinical Policy at Biologics. Other blood therapies approved include Genetech s GAZYVA (obinutuzumab), which was approved in combination with chlorambucil for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL), and Celgene s Pomalyst for third line multiple myeloma. GAZYVA has an average wholesale price (AWP) of $41,300 per cycle, while Pomalyst averages $12,534 per cycle. Another lymphoma drug that received attention in 2013 was ARIAD s Iclusig (ponatinib). Originally approved on December 14, 2012 for adult patients with chronic, accelerated, or blast phase chronic myeloid leukemia or Philadelphia-chromosome
2013 Drug Approval Breakdown Drug Name Manufacturer Indication Genetics Route of Administration Mechanism Clinical Trial Results Average Wholesale Price per Cycle (AWP) Xofigo Bayer Algeta Prostate bone metastases (1st Line) N/A IV Radiopharmaceutical Extended Overall Survival; a median average of 14 months compared to 11.2 months in the placebo arm $82,800 for a single treatment course Pomalyst Celgene Multiple myeloma (3rd Line) N/A PO Immune modulator, antiangiogenic median 4 vs. 1.9 months, Overall Survival median 12.7 vs. 8.1 months $12,534 Tafinlar GSK Metastatic or unresectable melanoma BRAF PO BRAF inhibitor Progression Free Survival was 5.1 months vs. 2.7 months $7,600 Mekinist GSK Metastatic melanoma (1st line) BRAF, MEK PO MEK inhibitor (MEK1, MEK2) was 4.8 months compared to 1.5 months $8,700 Kadcyla Roche/ Genentech/ Metastatic breast 2nd Line HER2 IV Chemo + mab conjugate Overall Survival was 30.9 months compared to 25.1 months $8,320 Immunogen Gilotrif Boehringer Ingelheim Non-small cell lung EGFR PO Tyrosine kinase inhibitor was 11.1 months vs. 6.9 months for those treated with pemetrexed/cisplatin N/A Xalkori Pfizer, Inc. Metastatic nonsmall cell lung ALK+ PO ALK inhibitor Progression free survival of 7.7 monoths compared with those getting chemotherapy which was 3.0 mo. The overall response rate was 65% in the Xalkori arm vs 20% in the chemotherapy arm $11,564
2013 Drug Approval Breakdown, continued Drug Name Manufacturer Indication Genetics Route of Administration Mechanism Clinical Trial Results Average Wholesale Price per Cycle (AWP) IMBRUVICA Pharmacyclics, Inc. Janssen Biotech, Inc. Mantle cell lymphoma 2nd line NCCN 2A for CLL/Sll and Waldenstrom s N/A PO Bruton s tyrosine kinase inhibitor Overall response rate of 65.8%, with 21% of patients achieving a complete response. Estimated PFS 13.9 months and estimated OS at 18 months was 58% $10,933 GAZYVA Genentech, Inc. Roche Previously untreated chronic lymphocytic leukemia in combination with chlorambucil N/A IV CD-20-directed cytolytic antibody GC vs C showed a PFS advantage of 23.0 months vs 11.1 months. In the follow up phase III study of G vs Mab/ Thera + Rituximab the results showed a PFS in the Gazyva arm of 26.7 months vs. 15.2 months $41,300 Iclusig ARIAD Pharmaceuticals, Inc. T3151 pos Chronic myeloid leukemia and T3151 Ph+ acute lymphoblastic leukemia T3151 PO Tyrosine kinase inhbitor Overall CCyR was 39% with the T3151 cohort having a 58% CCyR $10,417 Source: Full Prescribing Information, Average Wholesale Price Targeted Therapy Being Used in Combination Originally approved in 2013 to treat metastatic melanoma, the FDA announced on January 9, 2014 that Tafinlar (trametinib) and Mekinist (dabrafenib), both from GlaxoSmithKline, were approved for use in combination for treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations making it the first approved combination of targeted therapies in metastatic melanoma. Combining agents that target different mechanisms regulating the growth of cells is one of the promising areas in research, said Dr. Paolo Paoletti, President of Oncology, GSK iii. Separately, the prices for each drug are below other comparable therapies, but the combination of the two push the price tag to over $16,300 per cycle.
More High-touch Specialty Distribution Network Models As more targeted therapies come to market to support unique, smaller patient populations, biopharma companies are using more high-touch, specialty pharmacies like Biologics as part of their distribution network. Pharmacyclics IMBRUVICA network includes five high-touch, independent pharmacies while ARIAD made the decision to go to a closed distribution network, partnering with Biologics exclusively. We believe Biologics approach to patient care and expertise within oncology will deliver the best value and experience to our patients and providers, said Marty J. Duvall, executive vice president and chief commercial officer at ARIAD. Our primary objective is to make sure that our patients can access, afford and adhere to this important medicine. Key Drug Name Manufacturer Disease State # of Pharmacies in Network Afinitor Novartis PNET, RCC, renal angiomyolipoma, TSC, SEGA Arimidex AstraZeneca Breast 40* Caprelsa AstraZeneca Medullary thyroid Biologics Exclusive Cometriq Exelixis, Inc. Metastatic medullary thyroid Diplomat Exclusive Erivedge Genentech BCC 13* Femara Novartis Breast Gleevec Novartis CML, ALL, MDS/MPD, ASM, HES, CEL, DFSP, GIST Hycamtin GSK Small cell lung 23* Iclusig ARIAD CML, Ph+ ALL Biologics Exclusive IMBRUVICA Pharmacyclics, Inc. Janssen Biotech, Inc. MCL 5* Inlyta Pfizer RCC 20* Jakafi Incyte Myelofibrosis 6 Mekinist GSK Melanoma 23* Nexavar Onyx/Bayer RCC, HCC 11 Pomalyst Celgene Multiple myeloma 28* Promacta GSK ITP 23* Revlimid Celgene Multiple myeloma, MDS 28* Sprycel Bristol-Myers Squibb CML, ALL Sutent Pfizer GIST, RCC, PNET Tafinlar GSK Melanoma 23* Tarceva Genentech NSCLC, Pancreatic 28* Tasigna Novartis CML Temodar MERCK GBM Thalomid Celgene Multiple myeloma, ENL 28* Tykerb GSK Breast 23* Votrient GSK RCC, Soft Tissue Sarcoma 23* Xalkori Pfizer NSCLC, ALK 5 Xeloda * Biologics is in network Genentech Colorectal, colon, breast Xtandi Astellas Prostate 18* Zelboraf Genentech Melanoma 13* Zolinza MERCK CTCL Zytiga Janssen Biotech, Inc. CRPC 16*
2014 Pipeline Outlook Biologics Clinical Therapeutic Intelligence team identified the following drugs as notable to watch for FDA approval in 2014. Idelalisib, Gilead s first-in-class inhibitor of phosphatidylinositol 3-kinase (PI3K), in phase I and II trials for CLL and SLL LDK378, Novartis anaplastic lymphoma kinase inhibitor for non-small cell lung, which received breakthrough status from the FDA Nivolumab, an investigational PD-1 immune checkpoint inhibitor by Bristol-Myers Squibb for melanoma MK-3475, MERCK s investigational anti-pd1 immunotherapy for advanced melanoma AP26113, Ariad s second generation ALK inhibitor for lung Buparlisib, a BKM120- PI3K inhibitor from Novartis for breast and gliomas LDE225, Novartis hedgehog inhibitor for basal cell carcinoma Apitolisib, Genentech s PI3K/mTOR inhibitor for prostate, endometrial and RCC INCB39110, Incyte s JAK 1 inhibitor for myelofibrosis and advanced s SAR302503, a JAK 2 inhibitor from Sanofi for myelofibrosis SAR245408, Sanofi s PI3K inhibitor for endometrial and breast s ENMD-2076, Entremed s TKI, for clear cell ovarian, as well as sarcoma and breast s Sources: i Ibrutinib, http://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm374857.htm, November 13, 2013 ii Ibrutinib s Breakthrough to Market, http://blog.pharmexec.com/2013/11/25/ibrutinibs-breakthrough-to-market/, November 25, 2013 iii GSK gains accelerated FDA approval for combination use of Mekinist (trametinib) and Tafinlar (dabrafenib), www.marketwatch.com/story/gsk-gains-accelerated-fda-approval-forcombination-use-of-mekinist-trametinib-and-tafinlar-dabrafenib-2014-01-08, January 8, 2014 More Information Sign up to receive additional information about the Oncology Pipeline, please email info@biologicsinc.com Contact Us Phone: 800.850.4306 Email: info@biologicsinc.com biologicsinc.com Biologics, Inc. 120 Weston Oaks Court Cary, NC 27513 Connect with us on LinkedIn, just search for Biologics, Inc. Follow us on Twitter, we re @BiologicsInc Like us on Facebook, just search for Biologics, Inc. Ver 1.00.012014