BTG Specialty Pharmaceuticals advances global regulatory program for glucarpidase, sold as Voraxaze® in the US

BTG Specialty Pharmaceuticals partner Ohara Pharmaceutical Co., Ltd. has obtained marketing authorization for glucarpidase in Japan

West Conshohocken, PA, 28 September 2021: BTG Specialty Pharmaceuticals announced that Ohara Pharmaceutical Co., Ltd. has obtained marketing authorization for glucarpidase from Japan's Ministry of Health, Labour and Welfare as a therapeutic agent for “detoxication in case of delayed methotrexate elimination with methotrexate-leucovorin rescue therapy,” on September 27, 2021. Ohara will sell glucarpidase in Japan with the branded name Megludase®.

The Japanese Ministry of Health, Labour and Welfare granted this authorization based on the efficacy and safety results of clinical studies conducted in Japan and overseas, including an investigator-initiated study known as CPG2-PII funded by the Japan Medical Association. Ohara has been responsible for the glucarpidase development program and registration in Japan under a 2011 licensing agreement with BTG.

Christon Hill, Vice President for Product Life Cycle Management, said: “There is an acute need for reliable rescue therapy for toxic methotrexate concentration in patients with delayed clearance due to impaired renal function. As we continue to achieve regulatory milestones that broaden the availability of glucarpidase globally, we grow more excited for Voraxaze’s potential to improve the care of cancer patients around the world.”

In August of 2020 BTG submitted a Marketing Authorisation Application for Voraxaze® (glucarpidase) with the European Medicines Agency (EMA) for the treatment of adults and children (from 28 days of age) at risk of methotrexate toxicity due to delayed methotrexate elimination. The EMA is reviewing the application under the centralized marketing authorization procedure. If approved Voraxaze® would receive marketing authorization in all member states of the European Union (EU), as well as in Iceland, Liechtenstein and Norway.

Marketed by BTG as Voraxaze® in the US, the US Food and Drug Administration granted marketing approval to glucarpidase in 2012. In the US, Voraxaze® is a carboxypeptidase indicated to reduce toxic plasma methotrexate concentration (greater than 1 micromole per liter) in adult and pediatric patients with delayed methotrexate clearance (plasma methotrexate concentrations greater than 2 standard deviations of the mean methotrexate excretion curve specific for the dose of methotrexate administered) due to impaired renal function.

Voraxaze® is also being independently studied in Europe and the US to explore whether routinely giving Voraxaze® in combination with high-dose methotrexate might alleviate toxicity, manage the risk to patients and help them to complete therapy. Enrollment in these studies is ongoing. For more information about these studies, or to contact an investigator about participation, please visit ClinicalTrials.gov.

About Ohara Pharmaceutical Co., Ltd.
Ohara Pharmaceutical Co., Ltd. is a pharmaceutical company that discovers and develops orphan drugs and generic drugs as its mainstay business. The company particularly focuses on the development, manufacturing and marketing of orphan drugs for pediatric cancer and other areas, and on the development, manufacturing and marketing of generic drugs that feature in the prevention of medical accidents. Ohara Pharmaceutical aims to become a company that provides a total healthcare solution by promoting innovations not only in treatment, but also for the prevention, diagnosis and aftercare that affect the quality of healthcare in the substantially changing healthcare environment and improving the treatment outcome.

About BTG Specialty Pharmaceuticals
BTG Specialty Pharmaceuticals provides antidotes that counteract the potentially life-threatening effects associated with exposure or overexposure to certain toxins. These acute care products are typically used in emergency rooms and intensive care units to treat patients for whom there are limited or no existing treatment options. We are dedicated to delivering quality medicines that make a real difference to patients through the development, manufacture, and commercialisation of pharmaceutical products. To learn more about BTG Pharmaceuticals, please visit: btgsp.com.

For further information contact:
Chris Sampson, Corporate Communications Director
chris.sampson@btgsp.com; Mobile: +44 (0)7773 251 178


VORAXAZE® INDICATION AND LIMITATIONS OF USE

• Voraxaze® is a carboxypeptidase indicated to reduce toxic plasma methotrexate concentration (greater than 1 micromole per liter) in adult and pediatric patients with delayed methotrexate clearance (plasma methotrexate concentrations greater than 2 standard deviations of the mean methotrexate excretion curve specific for the dose of methotrexate administered) due to impaired renal function

• Limitations of Use: Voraxaze® is not recommended for use in patients who exhibit the expected clearance and expected plasma methotrexate concentration. Reducing plasma methotrexate concentration in these patients may result in subtherapeutic exposure to methotrexate

IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS

Serious Hypersensitivity Reactions

• Serious hypersensitivity reactions, including anaphylactic reactions, may occur. Serious hypersensitivity reactions occurred in less than 1% of patients

Monitoring Methotrexate Concentration/Interference with Assay

• Methotrexate concentrations within 48 hours following Voraxaze® administration can only be reliably measured by a chromatographic method due to interference from metabolites. Measurement of methotrexate concentrations within 48 hours of Voraxaze® administration using immunoassays results in an overestimation of the methotrexate concentration

ADVERSE REACTIONS

• In clinical trials, the most common related adverse events (occurring in >1% of patients) were paresthesia, flushing, nausea and/or vomiting, hypotension and headache

DRUG INTERACTIONS

• Voraxaze® can decrease leucovorin concentration, which may decrease the effect of leucovorin rescue unless leucovorin is dosed as recommended, and may also reduce the concentrations other folate analogs or folate analog metabolic inhibitors

Please see full Prescribing Information.

References:

1. Widemann BC, Balis FM, Kim A, et al. Glucarpidase, leucovorin, and thymidine for high-dose methotrexate-induced renal dysfunction: clinical and pharmacologic factors affecting outcome. J Clin Oncol. 2010;28(25):3979-3986.

2. 2013 Annual Meeting of the North American Congress of Clinical Toxicology (NACCT). Clin Toxicol. 2013;51(7):575-724.

3. Voraxaze® [prescribing information]. BTG International Inc.; 2019.

4. Howard SC, McCormick J, Pui CH, et al. Preventing and managing toxicities of high-dose methotrexate. Oncologist. 2016;21(12):1471-1482.

5. Demiralp B, Koenig L, Kala J, et al. Length of stay, mortality, and readmissions among Medicare cancer patients treated with glucarpidase and conventional care: a retrospective study. Clinicoecon Outcomes Res. 2019;11:129-144.