Bleomycin Hydrochloride

Takeda UK has announced that the National Institute for Health and Care Excellence (NICE) has recommended Adcetris (brentuximab vedotin) as part of a combination treatment for adults with untreated Hodgkin lymphoma (HL). The health technology assessment agency has recommended in final draft guidance that Adcetris be used on the NHS alongside doxorubicin, vinblastine and dacarbazine (AVD) to treat patients with untreated stage 3 or 4 CD30-positive HL. The decision makes Adcetris the first drug to be recommended specifically for previously untreated late-stage classical HL and follows an “improved confidential discount” on the treatment’s list price offered by Takeda, NICE said. HL is a relatively aggressive cancer that occurs when white blood cells called lymphocytes grow out of control. Approximately 2,100 cases are diagnosed in the UK every year, and around 800 people are diagnosed with stage 3 or 4 disease. Adcetris belongs to a class of drugs called antibody-drug conjugates, which combine the selectivity of antibodies with the potent cell-killing power of chemotherapy or other anti-cancer agents. Given as an infusion into a vein, Adcetris specifically targets human CD30-positive tumour cells and will be available immediately through the Cancer Drugs Fund. NICE’s recommendation of the drug was supported by positive results from the late-stage ECHELON-1 trial, which compared Adcetris plus AVD to doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) in more than 1,300 adults with untreated stage 3 or 4 HL. The study met its primary endpoints, with Adcetris plus AVD demonstrating a statistically significant improvement in modified progression-free survival compared to ABVD. The trial also achieved its key secondary endpoint of overall survival, and the tolerability profile observed with the combination was generally manageable. Emma Roffe, oncology country head, Takeda UK & Ireland said: “[Adcetris] is a medicine that continues to transform the treatment paradigm for patients with HL. We are committed to working in partnership with the clinical and patient community, NICE and the NHS, to ensure as many eligible patients as possible can gain access to this medicine. “We are delighted that NICE recognised the benefit this regimen may bring to patients newly diagnosed with this aggressive disease.” Takeda is responsible for Adcetris’ commercialisation everywhere except in the US and Canada, where Pfizer holds commercialisation rights.

On November 10, 2022, the Food and Drug Administration approved brentuximab vedotin (Adcetris, Seagen, Inc.) in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide for pediatric patients 2 years of age and older with previously untreated high risk classical Hodgkin lymphoma (cHL). This is the first pediatric approval for brentuximab vedotin. Efficacy was evaluated in a randomized, open-label, actively controlled trial. High risk was identified as Ann Arbor Stage IIB with bulk disease, Stage IIIB, Stage IVA, and Stage IVB. Of the 600 total patients randomized, 300 were randomized to brentuximab vedotin plus doxorubicin (A), vincristine (V), etoposide (E), prednisone (P), and cyclophosphamide (C) [brentuximab vedotin + AVEPC], and 300 patients were randomized to A+bleomycin (B)+V+E+P+C [ABVE-PC] arm. Patients in each treatment arm received up to 5 cycles of the following: Brentuximab vedotin + AVEPC arm: brentuximab vedotin 1.8 mg/kg over 30 minutes (day 1), doxorubicin 25 mg/m2 (days 1 and 2), vincristine 1.4 mg/m2 (day 8), etoposide 125 mg/m2(days 1-3), prednisone 20 mg/m2 BID (days 1-7), cyclophosphamide 600 mg/m2 (days 1 and 2); or ABVE-PC arm: doxorubicin 25 mg/m2 (days 1 and 2), bleomycin 5 units/m2 (day1) and 10 units/m2 (day 8), vincristine 1.4 mg/m2 (days 1 and 8), etoposide 125 mg/m2 (days 1-3), prednisone 20 mg/m2 BID (days 1-7), cyclophosphamide 600 mg/m2 (days 1 and 2). The main efficacy outcome measure was event-free survival (EFS), defined as the time from randomization to the earliest of disease progression or relapse, second malignancy, or death due to any cause. Median EFS was not reached in either arm. There were 23 events (8%) in the brentuximab vedotin + AVEPC arm and 52 events (17%) in the ABVE-PC arm with a corresponding hazard ratio of 0.41 (95% CI: 0.25, 0.67; p=0.0002). The most common Grade ≥3 adverse reactions (≥5%) in pediatric patients treated with brentuximab vedotin in combination with AVEPC were neutropenia, anemia, thrombocytopenia, febrile neutropenia, stomatitis, and infection. The recommended brentuximab vedotin dose for pediatric patients 2 years of age and older is 1.8 mg/kg up to a maximum of 180 mg in combination with AVEPC every 3 weeks for a maximum of 5 doses. View full prescribing information for Adcetris. This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. Brentuximab vedotin has orphan drug designation for the treatment of Hodgkin lymphoma. Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088. For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov. For information on the COVID-19 pandemic, see the following resources: FDA: Coronavirus Disease 2019 (COVID-19) NCI: Coronavirus: What People With Cancer Should Know CDC: Coronavirus (COVID-19) Follow the Oncology Center of Excellence on Twitter @FDAOncologyExternal Link Disclaimer.