Vaccines for Alzheimer’s: exploiting similarities with Down syndrome

Pharmaceutical Technology | September 20, 2019

One approach to overcome continuing challenges facing drug research and development for Alzheimer’s is a vaccine. Swiss AC Immune has developed an Abeta-focused vaccine called ACI-24, which shown to be both effective and safe in pre-clinical models. As well as studying ACI-24 in Alzheimer’s patients, the company is investigating the candidate in Down syndrome patients who have a genetic predisposition to developing Alzheimer’s and are a more homogenous patient group. Believed to be caused by the build-up of plaques in the brain consisting of fibrillary amyloid beta (ABeta) peptides and neurofibrillary tangles of tau proteins, Alzheimer’s disease affects approximately 50 million people globally and is the leading cause of dementia. Despite its prevalence, academic researchers and the pharmaceutical industry have struggled to develop effective therapies against Alzheimer’s disease, with many drugs failing in late stage clinical trials. Research carried out between 2002 and 2012 concluded that the condition has a 99.6% trial failure rate.

Spotlight

Ever wondered what West’s cutting-edge product development facilities look like on the inside? Jeff Kyle, Sr. Director Operations and Supply Chain, and Tom McLean, VP Development Engineering, take you behind the scenes of the Scottsdale, AZ plant.

Spotlight

Ever wondered what West’s cutting-edge product development facilities look like on the inside? Jeff Kyle, Sr. Director Operations and Supply Chain, and Tom McLean, VP Development Engineering, take you behind the scenes of the Scottsdale, AZ plant.

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BUSINESS INSIGHTS

Karo Pharma acquires OTC brand portfolio from Teva Pharmaceuticals

Karo Pharma, Teva Pharmaceuticals | February 04, 2021

Karo Pharma Aktiebolag ("Karo") today reports the securing of an OTC brand portfolio containing Flux®, Decubal®, Lactocare®, Apobase®, Dailycare® and Fludent® from Teva Pharmaceuticals (Teva) for an absolute thought of EUR 84m. The exchange moves responsibility for brand portfolio, included Flux®, Decubal®, Lactocare®, Apobase®, Dailycare® and Fludent® from Teva to Karo. The brands created deals barely shy of EUR 35m in 2020 on a worldwide premise. The greater part is created in the Nordic business sectors, including Scandinavia, where the brands as of now are dispersed and showcased by Karo under a 7-year permit arrangement that was endorsed in the spring of 2019. The exchange adds around EUR 4m in net deals from new business sectors outside of Scandinavia of which approx. 80% is in Finland. The exchange disentangles the business set-up and gives Karo control of the resources, in this way preparing for long haul advancement of the brands and the worth chain. As far as monetary effect Karo will acknowledge direct investment funds in year 1 of simply under EUR 5m as expenses to Teva are disposed of. Karo as of now popularizes the items in Scandinavia and has dynamic associations with the agreement manufacturers that supply the brands. Subsequently, restricted added expenses and faculty are needed as an immediate aftereffect of the exchange. "The transaction is in full alignment with our strategy of owning and commercializing strong OTC brands within everyday healthcare. It gives us full global control of a very exciting brand portfolio that we will develop and optimize over the next years. It strengthens our position in the Nordic markets and notably it expands our business in Finland where we did not previously control these brands. Over the next years we shall expand life cycle management opportunities, drive activation across more channels and explore geographical market expansion", says Christoffer Lorenzen, CEO of Karo Pharma. The obtaining is an unadulterated resource bargain. No staff or assembling locales are incorporated, which limits business just as the innovation move chances. The exchange, which is financed with existing money and requires no extra credit facilities, is relied upon to close on April 1. About Karo Pharma Karo Pharma delivers smart choices for everyday healthcare. We own and commercialize branded, original over-the-counter products and prescription medicines. Our products are available in more than 60 countries, with Europe and the Nordic region as our core markets. Karo Pharma is headquartered in Stockholm, Sweden and listed on Nasdaq Stockholm Mid Cap.

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PHARMACY MARKET

Xeris Pharmaceuticals Completes Enrollment of Its Phase 1 Study of Levothyroxine (XP-8121)

Xeris Pharmaceuticals, Inc. | September 01, 2021

Xeris Pharmaceuticals, Inc., a specialty pharmaceutical company leveraging its novel formulation technology platforms to develop and commercialize ready-to-use injectable drug formulations, today announced that the company has completed enrollment and successfully dosed all participants in a Phase 1 study of levothyroxine (XP-8121) to evaluate the pharmacokinetics, safety and tolerability, and potential for weekly dosing of the investigational, novel, subcutaneous (SC) injection for the treatment of hypothyroidism. XP-8121 is a novel formulation that could potentially mitigate many of the challenges associated with oral formulations, such as identification of an ideal dose due to absorption variation and medication adherence for patients who have difficulty maintaining a stable, therapeutic serum level. Preclinical studies of SC XP-8121 showed a sustained plasma exposure profile and similar maximum plasma concentration (Cmax) when compared with equivalent doses of the oral formulation. The Phase 1 clinical study of levothyroxine (XP-8121) is a single ascending dose crossover design in 30 healthy participants to compare matching doses of oral levothyroxine (Synthroid®) and subcutaneous (SC) XP-8121. The primary endpoints of the study are to characterize the absorption and elimination kinetics of XP-8121 and compare bioavailability of XP-8121 to oral levothyroxine. Secondary endpoints are safety and tolerability of XP-8121. The study is being conducted in partnership with Dr. Danielle Armas and Celerion, a leading contract research organization with extensive experience performing first-in-human studies. “The potential for a once weekly subcutaneous injection of levothyroxine would represent a promising novel approach in treating patients with hypothyroidism. Drug non-compliance, resistant hypothyroidism, and limited GI absorption are some of the major reasons for treatment failure or suboptimal treatment with oral levothyroxine. These challenges could be mitigated by XP-8121 and translate into the long-term health benefit of achieving a euthyroid state for patients,” said Dr. Armas, Senior Principal Investigator, Celerion. “Because our levothyroxine formulation enables a small volume SC injection, as an injectable maintenance therapy, it may facilitate less frequent dosing. This may provide clinical advantages over the established oral daily route, by providing predictable bioavailability, comparable safety, and ease of use,” said Dr. Ken Johnson, Xeris’ Senior Vice President of Global Development and Medical Affairs. About Levothyroxine and Hypothyroidism. The thyroid gland is responsible for the synthesis, storage, and release of metabolic hormones including thyroxine (T4) and triiodothyronine (T3) [Colucci et al, 2013]. These hormones are crucial in the regulation of critical metabolic processes and are vital for normal growth and development during fetal life, infancy, and childhood. Therapeutically, levothyroxine is administered when the body is deficient in the endogenous hormone. The goal of therapy is restoration of the euthyroid state which can reverse the clinical manifestations of hypothyroidism and significantly improve quality of life [Winther et al, 2016]. The treatment of choice for correction of hypothyroidism is levothyroxine, which is the mainstay of thyroid hormone replacement therapy. It is one of the most widely prescribed drug products in the United States, but the complexity of maintaining biochemical and clinical euthyroidism in patients undergoing treatment with oral levothyroxine cannot be underestimated. It has been reported that nearly 40% of patients undergoing treatment with oral levothyroxine are either over- or under-treated [Laurent et al, 2018] due to factors that include, but are not limited to, drug formulation, use of the drug with food, adherence to the drug, use of concomitant medications, and pre-existing medical conditions. Many patients failing to reach target TSH levels are generally managed by simply increasing their levothyroxine daily dose [Chiovato et al, 2019]. However, levothyroxine is a drug with a narrow therapeutic index [Vita et al, 2014], meaning that relatively small deviations from the proper dose can cause a clinically meaningful shift in pharmacological effects when administered to a patient; thus, the titration of levothyroxine oral drug may be a tailored and incremental process. About Xeris Pharmaceuticals, Inc. Xeris is a pharmaceutical company delivering innovative solutions to simplify the experience of administering important therapies that people rely on every day around the world. With a novel technology platform that enables ready-to-use, room-temperature stable formulations of injectable drug, the company is advancing a portfolio of solutions in various therapeutic categories, including its first commercial product, Gvoke® in the U.S. Its proprietary XeriSol™ and XeriJect™ formulation technologies have the potential to offer distinct advantages over conventional product formulations, including eliminating the need for reconstitution, enabling long-term, room-temperature stability, significantly reducing injection volume, and eliminating the requirement for intravenous (IV) infusion. With Xeris’ technology, new product formulations are designed to be easier to use by patients, caregivers, and health practitioners and help reduce costs for payers and the healthcare system. Xeris is headquartered in Chicago, IL.

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PHARMACY MARKET

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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