13 minute read
CLINICAL PR
EMPAGLIFLOZIN (JARDIANCE®) APPROVED IN IRELAND FOR THE TREATMENT OF HEART FAILURE WITH REDUCED EJECTION FRACTION
The European Commission has granted marketing authorisation for Empagliflozin (Jardiance®) as a treatment for adults with symptomatic chronic heart failure with reduced ejection fraction (systolic heart failure) in Ireland, Boehringer Ingelheim and Eli Lilly and Company have announced. The extension of the indication follows a positive recommendation by the Committee for Medicinal Products for Human Use (CHMP) on 20 May 2021.
Marketing authorisation is based on results from the EMPEROR-Reduced trial in which empagliflozin showed a significant 25 percent reduction (ARR 5.2%) in the combined relative risk versus placebo of cardiovascular death or hospitalisation due to heart failure. The findings from the primary endpoint were consistent in subgroups with or without type 2 diabetes. Key secondary endpoint analyses from the trial demonstrated that empagliflozin reduced the relative risk of first and recurrent hospitalisation for heart failure by 30 percent (ARR 8.7%) and significantly slowed kidney function decline.
“Empagliflozin was the first SGLT2 inhibitor to demonstrate cardiovascular protective effects and improve cardiovascular outcomes in patients with type 2 diabetes,” said Dr Douglas Clark, Head of Medical Affairs for UK and Ireland at Boehringer Ingelheim. “We are delighted to now be able to offer empagliflozin to people with heart failure with reduced ejection fraction, regardless of diabetes status, and to provide an additional treatment option for the thousands of people who live with heart failure and important metabolic conditions. We look forward to collaborating with NCPE to ensure access to this trusted therapy.”
Heart failure is often associated with other diseases of the cardiorenal-metabolic systems such as type 2 diabetes and kidney disease. Due to the interconnected nature of these systems, improvement in one system can lead to positive effects throughout the others. Heart failure is a very common and severe complication of a heart attack and occurs when the heart cannot pump sufficient blood to the rest of the body.[iv],[v] There are two forms of the condition; heart failure with reduced ejection fraction means the heart cannot contract normally, while preserved ejection fraction means the heart cannot properly fill with blood. People with heart failure often experience breathlessness and fatigue, which can severely impact their quality of life.
The EMPEROR-Reduced trial is part of the EMPOWER clinical programme, exploring the impact of empagliflozin on the lives of people across the spectrum of cardio-renal-metabolic conditions. The safety profile was similar to the established safety profile of empagliflozin.
DUPIXENT® (DUPILUMAB) SMPC UPDATED WITH LONGTERM DATA REINFORCING WELL-ESTABLISHED SAFETY PROFILE IN ADULTS WITH MODERATE-TO-SEVERE ATOPIC DERMATITIS
Long-term safety data from a study of adults with moderate-tosevere atopic dermatitis treated with Dupixent will be added to the Dupixent Summary of Product Characteristics (SmPC) following a positive opinion issued by the European Medicines Agency's Committee for Medicinal Products for Human Use.
Data from a single-arm Phase 3 open label extension (OLE) trial showed the long-term safety profile in adults with moderate-tosevere atopic dermatitis treated with Dupixent and observed up to three years was generally consistent with what was observed in the controlled pivotal Phase 3 trials. The OLE trial assessed the long-term safety of Dupixent 300 mg weekly in adults who had previously participated in Dupixent trials or had been screened for a Phase 3 trial. The approved Dupixent dose in adults is 300 mg every other week.
Atopic dermatitis is a chronic inflammatory disease of the skin that can be debilitating. Moderate-to-severe atopic dermatitis is characterized by intense persistent itch and skin lesions that can cover much of the body, resulting in skin dryness, cracking, redness or darkening, crusting and oozing. Itch is one of the most burdensome symptoms for patients. Moderate-to-severe atopic dermatitis can also have a substantial emotional and psychosocial impact on patients and their families, causing sleep disturbance, anxiety, depression and feelings of isolation.
Dupixent is the only biologic approved in the EU for children as young as six with severe atopic dermatitis and for adolescents and adults with moderate-tosevere atopic dermatitis who are candidates for systemic therapy. Dupixent is a fully human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) proteins. IL-4 and IL-13 are key and central drivers of the type 2 inflammation that plays a major role in atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP) and eosinophilic esophagitis (EoE). Dupixent is not an immunosuppressant and does not require ongoing lab monitoring. Dupixent is currently approved in more than 60 countries, and more than 260,000 patients have been treated globally.
HSE REIMBURSES NEW SUBCUTANEOUS FORMULATION OF TYSABRITM (NATALIZUMAB) TO TREAT ADULTS LIVING WITH HIGHLY ACTIVE RELAPSING REMITTING-MULTIPLE SCLEROSIS
Biogen Ireland have announced that the HSE has agreed to reimburse a subcutaneous (SC) injection of TYSABRITM (natalizumab) for adults living with highly active relapsing-remitting multiple sclerosis (MS).
The announcement follows the European Commission’s (EC) decision on the 30th March 2021 meaning that the new route of administration is now approved in Ireland.
Natalizumab SC offers comparable efficacy and safety and builds on the long-term data and established clinical benefits of the natalizumab intravenous (IV) formulation. Natalizumab is the only high-efficacy disease modifying therapy for RRMS that offers two routes of administration providing patients and healthcare professionals (HCPs) with the flexibility to choose the one that best fits their individual needs.
The SC and IV formulations of natalizumab 300 mg, are administered once every four weeks by a HCP in a clinical setting.
The new SC formulation expands the clinical setting beyond infusion centres, potentially bringing care closer to home, e.g., via community healthcare centres, offering patients treatment convenience whilst still providing medical oversight of treatment administration.
The administration by a HCP allows for ongoing disease monitoring, including screening for progressive multifocal leukoencephalopathy (PML), identifying and treating potential hypersensitivity reactions and ensuring adherence to treatment. As well as the shorter SC administration time, compared to the IV formulation, the SC injections also provide the option for HCPs to reduce or remove the 1-hour post-dose observation period, after the first six doses, based on clinical judgement. “This is an important treatment option for people living with MS, as it provides individuals with more flexibility around how they would like to receive their treatment. It still provides people with the opportunity to access their MS Care team but will minimise the time spent receiving treatment and can potentially be administered in more convenient locations, closer to home” said Ava Battles, CEO, MS Ireland.
The approval of the SC route of administration for natalizumab is based on data from the DELIVER (Phase 1) and REFINE (Phase 2) studies.
The SC formulation of natalizumab 300 mg has shown comparability to the Q4W IV administration of 300mg natalizumab in efficacy, pharmacokinetic (PK) and pharmacodynamic (PD) profiles. The safety of natalizumab SC in both the DELIVER and REFINE studies was generally consistent with the well-established benefitrisk profile of natalizumab IV in other clinical studies and the post-marketing setting, with the exception of injection site pain which can occur with SC injections. “This unprecedented year has put the HSE under significant resource pressures and created new challenges for those living with long-term conditions, like MS, when accessing vital, life impacting treatments,” said Dr Bronagh Hayden, Head of Medical Affairs Biogen Ireland. “As our healthcare and everyday environment evolves, we must continue to provide solutions to address capacity and resource concerns within the health service, whilst addressing patient needs. Reinforced by nearly 15 years of real-world evidence and post marketing experience with natalizumab IV, SC offers a new method of delivery that can help to reduce patient time in a hospital setting and increase convenience in clinical practice.”
LEO PHARMA ANNOUNCES
MHRA AND EC APPROVAL OF ADTRALZA (TRALOKINUMAB)
LEO Pharma UK and Ireland, a leader in medical dermatology, has announced that the Medicines and Healthcare products Regulatory Agency (MHRA) and the European
Commission (EC) has approved tralokinumab for the treatment of moderate-to-severe atopic dermatitis in adult patients who are candidates for systemic therapy.
The MHRA and EC approvals make tralokinumab the first and only approved biologic that specifically targets the IL-13 cytokine alone, a key driver of atopic dermatitis signs and symptoms.
Tralokinumab is the first high affinity, human monoclonal antibody developed to specifically bind to and inhibit the IL-13 cytokine in adult patients with uncontrolled moderate-to-severe atopic dermatitis. Tralokinumab AD. 5 Safety data was evaluated from a pool of five randomized, double-blind, placebo-controlled trials, including ECZTRA 1, 2 and ECZTRA 3, a dose ranging trial, and a vaccine response trial.5 LEO Pharma is working closely with key stakeholders to support access to tralokinumab for eligible patients.
The MHRA and EC decisions are valid in the UK and all European Union Member States, Iceland, Norway, and Liechtenstein. Additional regulatory filings are underway with [the U.S. Food and Drug Administration (FDA) and other] health authorities worldwide.
will be available in a 150 mg/mL prefilled syringe for subcutaneous injection with an initial dose of 600 mg followed by 300 mg every other week.
Tralokinumab can be used with or without topical corticosteroids (TCS). “Atopic dermatitis can be an intensely itchy, challenging and unpredictable skin condition for some. As clinicians, we always want more options for patients and the approval of tralokinumab means that clinicians across the UK and Ireland now have an important new treatment option for patients with moderate-to-severe atopic dermatitis in adult patients” said Professor Anthony Bewley, Consultant Dermatologist at Barts Health NHS Trust.
Dr Amit Aggarwal, Medical Director, LEO Pharma UK and Ireland said, “Tralokinumab was developed based on the advanced understanding of the immune processes underlying atopic dermatitis, which is fundamental to our mission of pioneering medical dermatology.”
]The approval is based primarily on safety and efficacy results from the ECZTRA 1, 2 and ECZTRA 3 pivotal Phase 3 trials, which included more than 1,900 adult patients with moderate-to-severe
NEED FOR SPEED IN CARDIAC ARREST PATIENTS
The quick action of team mates and officials to save the life of Danish footballer Christian Eriksen has highlighted the need for bystanders to react with speed to a cardiac arrest, the Irish Heart Foundation insisted recently. Eriksen collapsed on Saturday during the first half of Denmark’s opening Euro 2020 match against Finland before being treated on the pitch and hospitalised. “We know that without CPR or a defibrillator, your chances of survival decrease by 10% every minute, so because of the quick actions of everyone around him, Christian Eriksen survived,” said Brigid Sinnott, Resuscitation Manager at the Irish Heart Foundation.
“He was fortunate that it happened in such a public place with people on hand to immediately begin CPR. “We know that 70% of cardiac arrests happen in the home, so it is vital that people understand what to do in that situation.
“Speed is of the essence – speed in recognising cardiac arrest, calling the emergency services, performing compressions and in using the AED (automated external defibrillator). It is the difference between life and death.
“In Christian Eriksen’s case, it was recognised early that he was having a cardiac arrest, he was helped immediately and they had a defibrillator on his chest very quickly. “And the fact that it was his teammates who were first to perform CPR on him before the medics got there, shows that anyone can do it." A cardiac arrest occurs when the heart beats fast and wildly or stops beating altogether. This can happen due to an abrupt disturbance in the heart’s internal electrical system that normally regulates the heartbeat. The heart cannot pump blood to the brain, lungs and other vital organs and without treatment, the outcome is usually fatal. Data from the 2019 Out-of-Home Cardiac Arrest Report shows that Ireland has bystander CPR rates (members of the public who perform CPR in such emergencies) of 84%. “If the electrics in your heart go wrong you need a defibrillator to reset them, while CPR compressions act as a pump for the heart,” said Ms Sinnott. “We need to get more defibrillators on chests and we would ask everyone to check where their nearest one is and whether it is accessible all the time.
“We have some easy to follow instructional videos on our website irishheart.ie and we encourage everyone to watch them, even if you have been trained in CPR in the past. “The first step in CPR is to call 112 or 999 and the second is to push hard and fast on the centre of the chest.
“It is really important for people to realise that they don’t have to be a trained doctor or medical professional to perform CPR – anybody can do it and you cannot do any harm.” As a leading training provider, the Irish Heart Foundation has courses across all the links in the chain of survival.
To find out more, go to www.irishheart.ie
Brigid Sinnott, Resuscitation Manager, Irish Heart Foundation
TAKEDA, RCPE, INSILICOTRIALS AND THE UNIVERSITY OF GRAZ PARTNER UP
Biopharmaceuticals are large and complex drugs that mimic the action of the molecular mechanisms in living organisms. In the past decade, the number of deaths due to cancer and HIV/AIDS have been significantly reduced and the treatment of several chronic diseases, such as diabetes and cardiovascular diseases, has been enhanced due to the emergence of biopharmaceuticals. Biopharmaceuticals represent one of the fastest growing segments in current drug pipelines, but their large-scale manufacturing and processing pose specific challenges to the drug formulation scientist, as these large and complex molecules are rather sensitive to variations of environmental conditions and process-induced stress. Filling is the final step of the manufacturing process for liquid protein formulations and the focus of this project. A 36-month joint project between the manufacturing site in Vienna of Takeda, one of the world's largest pharmaceutical companies, the Research Center Pharmaceutical Engineering (RCPE), the technology company InSilicoTrials, and the University of Graz has been initiated to establish the mechanistic basis of the relationship between process parameters and the effect of the resulting stresses on the characteristics of protein based drugs. Takeda and RCPE are in the process of building an ongoing partnership which has been and is currently being used to increase the scientific knowledge for biopharmaceutical products and processes. This project will enhance the understanding of the processinduced mechanisms for proteinbased biopharmaceuticals. Participation in collaborative programs of this kind will also be supportive to product and process development of protein-based drugs in the future, resulting in reduced material requirements and drug development timelines. This collaboration will adopt an innovative approach between Takeda and the partner companies where a lab scale version of one of Takeda's filling line will be designed and assembled. The line will be used to simulate the Takeda filling process on a smaller scale, comparing the effect of various settings of process parameters (filling speed, vial shape, protein concentration etc.). In addition, computational fluid dynamics simulations will be performed to estimate the shear forces, as well as size and dynamics of interfaces the concentrated protein solution is exposed to during the filling process. The generated experimental and simulation data will then be used to train and test algorithms based on state of the art machine learning models, to predict the potential impact of these parameters on the properties of the protein molecule. The final goal is a set of in-silico tools that can be used to guide the design and parameterization of the filling process.
COVID HEROES NOMINATE TODAY
IPN are looking for your nominations for Ireland’s Pharmacy industry’s most inspiring and enthusiastic people.
Do you know someone who has
went above and beyond in Pharmacy?
Who deserved recognition
for a special project they have executed?
Who has shown an ability to
get things done during a period of change?
Who has developed something
