Mercks new combo med Recarbrio fights resistant bacteria. Can it tackle the sales challenge, too?

fiercepharma | July 17, 2019

Mercks new combo med Recarbrio fights resistant bacteria. Can it tackle the sales challenge, too?
Merck and Co. is one of the few large drugmakers still pursuing antibacterial R and D, and on Wednesday, the company scored approval for a combo drug that tackles serious urinary tract and abdominal infections when other treatments don't work. The FDA signed off on Merck’s Recarbrio, which adds a new infection-fighter, relebactam, to a previously approved combo of cilastatin and imipenem. The three-ingredient combo med has a green light to tackle infections in adults caused by specific gram-negative bacteria. Merck's newest nod comes on the heels of a Zerbaxa label expansion last month. The FDA added certain types of pneumonia to Zerbaxa's list of approvals in complicated UTIs and abdominal infections. The label boost gives Zerbaxa, acquired in Merck's $8.5 billion Cubist buyout, a chance to make up for early sales shortfalls. Zerbaxa's marketing struggles show one reason why so many drugmakers are abandoning anti-infective research, even at a time when the need for new meds is so great. Speaking with FiercePharma earlier this summer, Merck’s associate vice president in infectious disease clinical research Dr. Joan Butterton said antibacterial resistance is “one of the great public health challenges of the modern era.” Recarbrio itself illustrates that challenge; it was developed to address imipenem's waning effectiveness. Adding relebactam to the mix restores bacteria's susceptibility to imipenem, a spokeswoman said. Imipenem and cilastatin have been approved in combo for decades as Primaxin.

Spotlight

Elemental impurities have been a hot topic since 2009 when the International Conference of Harmonisation (ICH) commenced work on a new standard to provide a global policy to limit these impurities in drug products and ingredients. Their guidance document, Q3D, reached step 4 in December 2014, meaning the final draft is recommended for adoption to the regulatory bodies of the European Union, Switzerland, Japan, USA and Canada. ICH Q3D provides a means of assessment and control of 24 elemental impurities using the principles of risk management as detailed in ICH Q9. It establishes permitted daily exposure (PDE) limits for each element, expressed in µg/day, calculated using published toxicity data and set according to the route of administration. The elements are divided into three classes based on their toxicity and likelihood of occurrence with limits applicable to finished formulations based on a maximum dosage of 10g/day. Compliance is not directly applicable to excipients or the drug substance, however, USP <232> does state “elemental impurity levels present in drug substances and excipients must be known, documented, and made available upon request.

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Sanofi's hopes for rare blood disease candidate sutimlimab on hold after FDA blasts 3rd-party manufacturer

Sanofi | November 17, 2020

When a new drug goes in front of the FDA for consideration, a lot of moving pieces must be in place for a successful review—manufacturing standards included. That didn't happen for Sanofi, which is pressing pause on a rare disease candidate after the FDA found issues at a contract manufacturer's plant. The FDA blasted a third-party manufacturer of Sanofi's rare blood disease drug sutimlimab in a complete response letter, citing "certain deficiencies" at the contractor's site, the French drugmaker said Friday. A Sanofi spokeswoman declined to specify who the manufacturer cited in the FDA's letter was or what the nature of the deficiencies were. With its application on hold, Sanofi said it would work with its manufacturer and the FDA to resolve the issues in a "timely manner." The drugmaker didn't say how quickly it expected to turn around a new application. The untimely feedback from the FDA dims C1 inhibitor sutimlimab's chances in cold agglutinin disease (CAD), a rare blood disease characterized by anemia, fatigue and other symptoms.

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Valemetostat New Drug Application Submitted in Japan for Treatment of Patients with Adult T-Cell Leukemia/Lymphoma

Daiichi Sankyo | December 29, 2021

Daiichi Sankyo Company, Limited announced that it has submitted a New Drug Application to Japan’s Ministry of Health, Labour and Welfare for valemetostat, a potential first-in-class dual inhibitor of EZH1 and EZH2, for the treatment of patients with relapsed/refractory adult T-cell leukemia/lymphoma. ATL is a rare and aggressive type of peripheral T-cell lymphoma that occurs with greater frequency in parts of Japan and other regions.1,2 Patients with ATL face a poor prognosis with current therapies.3 Nearly 90% of patients relapse after completing intensive first-line treatment, at which point there are few options available.1,4 The Japan NDA submission of valemetostat is based on pivotal phase 2 study results in Japanese patients with three aggressive subtypes of relapsed/refractory ATL, recently presented at the 2021 American Society of Hematology (ASH) Annual Meeting. Valemetostat previously received Orphan Drug designation from the Japan MHLW for treatment of patients with relapsed/refractory ATL. “Valemetostat would potentially be the first dual inhibitor of EZH1 and EZH2 to be approved anywhere in the world and could provide a new type of targeted therapy option for patients with relapsed/refractory ATL, which represents one of the most significant unmet medical needs in Japan. Valemetostat is the fifth innovative oncology medicine from our pipeline to be submitted for regulatory approval in Japan in the past three years.” Wataru Takasaki, PhD, Executive Officer, Head of R&D Division in Japan, Daiichi Sankyo About Adult T-Cell Leukemia/Lymphoma Adult T-cell leukemia/lymphoma is a rare and aggressive type of peripheral T-cell lymphoma that is caused by human T-cell lymphotropic virus type 1.1 More than 3,000 new cases of ATL are diagnosed each year worldwide.5 ATL occurs with greater frequency in regions where the HTLV-1 virus is endemic including southwest Japan, Central and South America and central Australia.3 Cases are also observed in North America and Europe, and incidence of ATL is rising in non-endemic areas.3 In Japan, there are approximately 1,000 new ATL cases and over 1,000 deaths due to ATL annually.6 ATL has the poorest prognosis compared to other types of PTCL, with a five-year overall survival rate of about 14%.7 A median survival time of approximately eight months (252 days) was reported for patients in Japan with the most common acute ATL subtype.5 Treatment of ATL is based on subtype and consists primarily of intensive multi-drug chemotherapy regimens.3 Nearly 90% of patients relapse after completing intensive first-line treatment, at which point there are few options available.1,4 Additional therapies are needed to improve the prognosis of ATL in Japan and worldwide.1,3 About Valemetostat Valemetostat is a potential first-in-class dual inhibitor of EZH1 and EZH2 currently in clinical development in the Alpha portfolio of Daiichi Sankyo. A potent and selective small molecule inhibitor, valemetostat is designed to counter epigenetic dysregulation by targeting both the EZH1 and EZH2 enzymes.8 The valemetostat development program includes VALENTINE-PTCL01, a global pivotal phase 2 trial in patients with relapsed/refractory PTCL and ATL; a pivotal phase 2 trial in patients with relapsed or refractory ATL in Japan; and, a phase 1 study in patients with relapsed/refractory NHL in the U.S. and Japan. Valemetostat received ODD from the U.S. Food & Drug Administration for the treatment of PTCL in December 2021, ODD from the Japan MHLW for the treatment of relapsed/refractory ATL in November 2021 and SAKIGAKE Designation from the Japan MHLW for the treatment of adult patients with relapsed/refractory PTCL in April 2019. Valemetostat is an investigational medicine that has not been approved for any indication in any country. Safety and efficacy have not been established. About the Pivotal Phase 2 Study The pivotal, open-label, multi-center, single-arm phase 2 study evaluated efficacy and safety of valemetostat as monotherapy in patients with relapsed/refractory ATL who were previously treated with mogamulizumab or at least one systemic chemotherapy in case of intolerance/ contraindication for mogamulizumab and with no history of allogenic hematopoietic stem cell transplant. The primary endpoint is objective response rate assessed by independent efficacy assessment committee. Secondary endpoints include investigator-assessed ORR, best response in tumor lesions, complete remission rate, tumor control rate, time to response, duration of response, progression-free survival, overall survival and safety. A total of 25 patients were enrolled in the study in Japan. About Daiichi Sankyo Oncology The oncology portfolio of Daiichi Sankyo is powered by our team of world-class scientists that push beyond traditional thinking to create transformative medicines for people with cancer. Anchored by our DXd antibody drug conjugate technology, our research engines include biologics, medicinal chemistry, modality and other research laboratories in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in the U.S. We also work alongside leading academic and business collaborators to further advance the understanding of cancer as Daiichi Sankyo builds towards our ambitious goal of becoming a global leader in oncology by 2025. About Daiichi Sankyo Daiichi Sankyo is dedicated to creating new modalities and innovative medicines by leveraging our world-class science and technology for our purpose “to contribute to the enrichment of quality of life around the world.” In addition to our current portfolio of medicines for cancer and cardiovascular disease, Daiichi Sankyo is primarily focused on developing novel therapies for people with cancer as well as other diseases with high unmet medical needs. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 16,000 employees around the world draw upon a rich legacy of innovation to realize our 2030 Vision to become an “Innovative Global Healthcare Company Contributing to the Sustainable Development of Society.”

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Citius Pharmaceuticals Achieves Chemical Manufacturing and Control Milestones for Mino-Lok

Citius Pharmaceuticals | September 23, 2020

Citius Pharmaceuticals, Inc. ("Citius" or the "Company") (Nasdaq: CTXR), a specialty pharmaceutical company focused on developing and commercializing critical care drug products, today announced that it has achieved a number of significant milestones over the past several weeks for Mino-Lok®. Mino-Lok is an antibiotic lock solution being developed as an adjunctive therapy for patients with central line-associated bloodstream infections (CLABSIs) or catheter-related bloodstream infections (CRBSIs). Mino-Lok contains three active drug substances (minocycline, ethanol and EDTA) which are combined into two vials, MLT01 (minocycline) and MLT02 (ethanol and EDTA). Citius has manufactured three registration lots of Mino-Lok using the commercial manufacturing process, which will be filed in the planned New Drug Application (NDA).

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Spotlight

Elemental impurities have been a hot topic since 2009 when the International Conference of Harmonisation (ICH) commenced work on a new standard to provide a global policy to limit these impurities in drug products and ingredients. Their guidance document, Q3D, reached step 4 in December 2014, meaning the final draft is recommended for adoption to the regulatory bodies of the European Union, Switzerland, Japan, USA and Canada. ICH Q3D provides a means of assessment and control of 24 elemental impurities using the principles of risk management as detailed in ICH Q9. It establishes permitted daily exposure (PDE) limits for each element, expressed in µg/day, calculated using published toxicity data and set according to the route of administration. The elements are divided into three classes based on their toxicity and likelihood of occurrence with limits applicable to finished formulations based on a maximum dosage of 10g/day. Compliance is not directly applicable to excipients or the drug substance, however, USP <232> does state “elemental impurity levels present in drug substances and excipients must be known, documented, and made available upon request.