Instant Report

Date: 25-Sep-2019

EMA committee recommends marketing approval for AstraZeneca's Qtrilmet to treat type-2 diabetes

AstraZeneca, a global, science-led biopharmaceutical company, announced that Qtrilmet (metformin hydrochloride, saxagliptin and dapagliflozin) modified-release tablets have been recommended for marketing authorisation in the European Union for the treatment of adults with type-2 diabetes (T2D). The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on data from five phase III trials which evaluated combinations of Forxiga (dapagliflozin) and Onglyza (saxagliptin) on a background of metformin in patients with inadequately-controlled T2D. The primary endpoint in these trials was mean change from baseline in HbA1c (average blood glucose levels) at week 24 or 52 Across the trials, the combination of Forxiga, Onglyza and metformin was superior in reducing HbA1c versus Forxiga combined with metformin, Onglyza combined with metformin, or glimepiride combined with metformin. The combination of Forxiga, Onglyza and metformin with or without sulphonylurea (SU) was non-inferior to the combined use of insulin and metformin with or without SU in reducing HbA1c.

Date: 20-Oct-2020

EMA Committee Recommends Marketing Approval For AstraZenecas Trixeo Aerosphere For Maintenance Treatment Of COPD

AstraZeneca’s Trixeo Aerosphere (formoterol fumarate/glycopyrronium bromide/budesonide) has been recommended for marketing authorisation in the European Union (EU) for maintenance treatment in adult patients with moderate to severe chronic obstructive pulmonary disease (COPD) who are not adequately treated by a combination of an inhaled corticosteroid (ICS) and long-acting beta2-agonist (LABA), or a combination of a LABA and a long-acting muscarinic antagonist.

Trixeo Aerosphere, a triple-combination therapy, is approved under the brand name Breztri Aerosphere in Japan, China and the US for patients with COPD.

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency based its positive opinion on results from the ETHOS phase III trial in which Trixeo Aerosphere showed a statistically significant reduction in the rate of moderate or severe exacerbations compared with dual-combination therapies Bevespi Aerosphere (glycopyrronium/formoterol fumarate) and PT009 (budesonide/formoterol fumarate) over 52 weeks.

The recommendation for approval was also supported by data from the KRONOS phase III trial. In both trials, the safety and tolerability of Trixeo Aerosphere were consistent with the profiles of the dual comparators.

Klaus Rabe, Professor of Pulmonary Medicine at the University of Kiel, Director of the Department of Pneumology at Clinic Grosshansdorf, Germany, Lead Investigator of the ETHOS trial and National Co-ordinating Investigator of the KRONOS phase III trial said, “Preventing exacerbations is central to the management of chronic obstructive pulmonary disease, as exacerbations may cause irreversible damage and disease progression. The triple-combination therapy, Trixeo Aerosphere, has demonstrated significant benefits in reducing moderate or severe exacerbations in patients suffering from this debilitating disease.”

Mene Pangalos, executive vice president, BioPharmaceuticals R&D, said, “Chronic obstructive pulmonary disease is now the third leading cause of death globally and affects approximately one in 10 adults over the age of 40 in Europe. Trixeo Aerosphere has demonstrated strong clinical benefit when compared with dual-combination therapies and this positive recommendation brings us closer to providing a much-needed new treatment to patients in Europe.”

COPD is a progressive disease which can cause obstruction of airflow in the lungs resulting in debilitating bouts of breathlessness. It affects an estimated 38 million people and is the third leading cause of death globally. In Europe, approximately 10% of adults over the age of 40 have COPD. Improving lung function, reducing exacerbations and managing daily symptoms such as breathlessness are important treatment goals in the management of COPD. A single COPD exacerbation can have a negative impact on lung function, quality of life and increase the risk of hospitalisation. Additionally, even one COPD exacerbation that results in hospitalisation increases the risk of death.

The ETHOS and KRONOS phase III trials are part of AstraZeneca’s ATHENA phase III clinical trial programme for Trixeo Aerosphere, which included more than 15,500 patients globally across 11 trials.

ETHOS is a randomised, double-blinded, multi-centre, parallel-group, 52-week phase III trial to assess the efficacy and safety of Trixeo Aerosphere in symptomatic patients with moderate to very severe COPD and a history of exacerbation(s) in the previous year. The primary endpoint was the rate of moderate or severe exacerbations.

KRONOS is a randomised, double-blinded, parallel-group, 24-week, chronic-dosing, multi-centre Phase III trial to assess the efficacy and safety of Trixeo Aerosphere in patients with moderate to very severe COPD regardless of whether or not they had an exacerbation in the previous year.

Trixeo Aerosphere (formoterol fumarate/glycopyrronium bromide/budesonide) is a single-inhaler, fixed dose triple-combination of formoterol fumarate, a LABA, glycopyrronium bromide, a LAMA, with budesonide, an ICS, and delivered in a pressurised metered-dose inhaler. Trixeo Aerosphere is approved under the brand name Breztri Aerosphere in Japan, China and the US for patients with COPD

Date: 02-Feb-2021

EMA Committee Recommends Marketing Approval For Novo Nordisks Once-weekly Sogroya To Treat AGHD

AstraZeneca announced that it will work with The Ethiopian Federal Ministry of Health and The Ethiopian Thoracic Society, as part of their new Africa PUMUA Initiative, aimed at redefining asthma care in Africa.

The Africa PUMUA Initiative looks at addressing the barriers currently preventing access to care for patients with asthma

The Initiative was designed in consultation and collaboration with government, healthcare societies and respiratory health experts to strengthen local health systems and centres to improve paediatric and adult asthma management across both the public and private sectors.  The Africa PUMUA Initiative will support fundamental changes needed to advance clinical practice aligned to the Non Communicable Disease (NCD) service decentralisation programme roll-out by the Ethiopian Federal Ministry of Health.  

Globally, more than 339 million people are living with asthma, with an estimated over 40 million people with asthma in Africa .The World Health Organisation (WHO) cautions that over 80% of asthma-related deaths occur in low-and lower-middle income countries.

AstraZeneca has launched the Africa PUMUA Initiative to highlight its commitment to improving the health outcomes of patients in Africa. By providing support of infrastructure, increasing awareness of the symptoms and risks of asthma, and building the capacity of all role players across the patient journey, the Africa PUMUA Initiative looks at addressing the barriers currently preventing access to care for patients with asthma.

As part of the partnership signed on 27 January 2021, with The Ethiopian Federal Ministry of Health and The Ethiopian Thoracic Society, AstraZeneca will provide 150 nebuliser machines to various hospitals within Ethiopia, as well as establish 47 nebulisation stations. The nebulisers will be allocated in consultation with the Ministry of Health and the Ethiopian Thoracic Society.

Barbara Nel, AstraZeneca country president for African Cluster said: “We are unwavering in our commitment to improve care for asthma patients across Africa.  People living with asthma should have the ability to live normal lives and deserve the best care. Through our Africa PUMUA initiative we aim to strengthen local health systems and centres. By working together to boost local medical knowledge and expertise and building an infrastructure for Asthma Patients, through the donation of nebulisation machines, nebulisation stations, spirometers and peak flow meters, we believe we will be able to redefine asthma care in Ethiopia.”

Dr Dereje Duguma , Ethiopian Federal Ministry of Health, said: Through this important Public-Private Partnerships with the AstraZeneca Pharmaceutical and the Ethiopian Thoracic Society we will bring immense transformation to Asthma care. The partnership also goes in line with the Government of Ethiopia’s National Strategic Action Plan for Non-Communicable Diseases, effective diagnosis and enhanced referral systems. PUMUA will be a great tool in decentralization of these efforts. We hope this will be a good start to collaborating with AstraZeneca and look forward to seeing more endeavours. MOH supports pharmaceutical companies investing in the country as it is one of the key strategic areas in developing industries in the country.”

“It is estimated that more than 5 million people in Ethiopia are living with asthma, and to date there has been no national treatment guidelines for the diagnosis and treatment of Asthma. The Ethiopian Thoracic Society strongly believes that the implementation of the Africa PUMUA initiative will contribute significantly to the effective diagnosis and management of asthma. The capacity building activities and the update and alignment of treatment guidelines and protocols for chronic asthma to GINA (Global Initiative for Asthma management) guidelines, will help to improve outcomes for asthma patients in Ethiopia. Cascading the treatment protocol and guidelines throughout the country will enable us provide standardised asthma diagnosis and treatment in Ethiopia,” said Ethiopian Thoracic Society President, Dr Tewodros Haile Gebremariam

The initiative will launch initially across 6 countries in Africa, including Ethiopia, Ghana, Kenya, Ivory Coast, Cameroon and Senegal, and then expand to other countries.

Date: 02-Mar-2021

EMA Committee Recommends Marketing Approval For Biocon Biologics & Viatris Biosimilar Bevacizumab

Biocon Biologics has announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the marketing authorization of their biosimilar bevacizumab, co-developed with Viatris, to be marketed as Abevmy (injection bevacizumab 100mg and 400mg).

Abevmy is a biosimilar to Roche’s Avastin, prescribed for all indications including metastatic colorectal carcinoma, metastatic breast cancer, non-small-cell lung carcinoma, glioblastoma, ovarian, cervical and renal cancer as part of a specific regimen.

The decision of the European Commission (EC) is expected in May 2021, which, when approved, will grant marketing authorization in the 27 European Union (EU) member countries and European Economic Area (EEA) member states of Norway, Iceland and Liechtenstein. For the UK, the Medicines and Healthcare Products Regulatory Agency’s ‘reliance procedure’ will be followed, and the UK marketing authorization can be expected shortly after the EC decision.

Kiran Mazumdar-Shaw, executive chairperson, Biocon Biologics, said: “CHMP's decision to recommend approval of our biosimilar bevacizumab brings us a step closer to enable affordable access to this biologic therapy for cancer patients in the EU along with our partner Viatris. It is an outcome of our commitment to expand access for patients leveraging our science and global scale manufacturing for a range of biosimilars. Through bTrastuzumab and bPegfilgrastim we are already making a difference to the lives of cancer patients in several EU countries. We look forward to a final decision from the European Commission approving biosimilar bevacizumab, which will add to our efforts in cancer care.”

Abevmy, bBevacizumab, is a recombinant “humanized” monoclonal antibody that selectively binds to human vascular endothelial growth factor (VEGF) and neutralizes its biologic activity. Bevacizumab inhibits the formation of tumor vasculature, thereby inhibiting tumor growth.

Date: 28-Apr-2021

EMA Committee Recommends Marketing Approval For Selumetinib To Treat Paediatric Patients With Neurofibromatosis Type 1 And Plexiform Neurofibromas

AstraZeneca and MSD’s selumetinib has been recommended for conditional marketing authorisation in the European Union (EU) for the treatment of symptomatic, inoperable plexiform neurofibromas (PN) in paediatric patients with neurofibromatosis type 1 (NF1) aged three years and above.

NF1 is a debilitating genetic condition affecting 1 in 3,000 individuals worldwide. In 30-50% of people with NF1, tumours develop on the nerve sheaths (plexiform neurofibromas) and can cause clinical issues such as disfigurement, motor dysfunction, pain, airway dysfunction, visual impairment, and bladder/bowel dysfunction.

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency based its positive opinion on results from the National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP)-sponsored SPRINT Stratum 1 phase II trial. Results were published in The New England Journal of Medicine. Safety and efficacy data from the SPRINT trial with longer follow up will be provided to the CHMP as a condition of the recommendation for approval.

The trial showed selumetinib demonstrated an objective response rate (ORR) of 66% (33 of 50 patients, confirmed partial response) in paediatric patients with NF1 PN when treated with selumetinib as twice-daily oral monotherapy.1 ORR is defined as the percentage of patients with confirmed complete or partial response of at least 20% reduction in tumour volume.

Dave Fredrickson, executive vice president, Oncology Business Unit said, “This recommendation means patients in the EU are one step closer to receiving the only approved medicine for neurofibromatosis type 1 and the only treatment outside of surgery, which is not an option for many patients. Children living with this rare genetic condition are in great need of novel treatment options to help address the impact of this disease.”

Roy Baynes, senior vice president and head of Global Clinical Development, chief medical officer, MSD Research Laboratories said, “In the SPRINT trial, selumetinib was shown to reduce the size of these inoperable tumours, a meaningful clinical advance for children living with this debilitating disease. We are pleased to be one step closer to bringing this important treatment option to these paediatric patients in the EU.”

Selumetinib was approved in the US in April 2020 for the treatment of paediatric patients with NF1 and symptomatic, inoperable PN under the medicine name Koselugo. Further regulatory submissions are underway. Clinical trials of selumetinib in adult patients with NF1 PN, and in an alternative age-appropriate formulation for paediatric patients, are scheduled to begin this year.

NF1 is caused by a spontaneous or inherited mutation in the NF1 gene and is associated with many symptoms, including soft lumps on and under the skin (cutaneous neurofibromas) and skin pigmentation (so-called ‘café au lait’ spots). In 30-50% of people, tumours develop on the nerve sheaths. These PN can cause clinical issues such as pain, motor dysfunction, airway dysfunction, bladder/bowel dysfunction and disfigurement as well as having the potential to transform into malignant peripheral nerve sheath tumours. PN begin developing during early childhood, with varying degrees of severity, and can reduce life expectancy by eight to 15 years.

The SPRINT Stratum 1 phase I/II trial was designed to evaluate the objective response rate and impact on patient-reported and functional outcomes in paediatric patients with NF1-related inoperable PNs treated with selumetinib monotherapy. This trial sponsored by NCI CTEP was conducted under a Cooperative Research and Development Agreement between NCI and AstraZeneca with additional support from Neurofibromatosis Therapeutic Acceleration Program (NTAP).

Selumetinib is an inhibitor of mitogen-activated protein kinase kinases 1 and 2 (MEK1/2). MEK1/2 proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway. Both MEK and ERK are critical components of the RAS-regulated RAF-MEK-ERK pathway, which is often activated in different types of cancers.

Date: 28-Jun-2021

EMA Committee Recommends Marketing Approval For BioMarinís Vosoritide To Treat Children With Achondroplasia From Age 2 Until Growth Plates Close

BioMarin Pharmaceutical Inc. announced that the Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending marketing authorization for vosoritide, a once daily injection analog of C-type Natriuretic Peptide (CNP) to treat achondroplasia in children from the age of 2 until growth plates are closed, which occurs after puberty when children reach final adult height.  Achondroplasia is the most common form of disproportionate short stature in humans.  A final approval decision, typically consistent with the CHMP recommendation, is expected from the European Commission in Q3 2021.  Vosoritide is potentially the first medicine to be approved to treat children with achondroplasia in Europe and would be marketed under the brand name Voxzogo (vosoritide).

It is estimated that over 11,000 children across Europe, Middle East, and Africa are affected by achondroplasia and eligible for treatment with vosoritide, if approved by a health authority.  Approximately a third of this population are in countries authorized to sell under the EMA license.  BioMarin anticipates additional patient access through named patient sales based on an EMA approval in countries in the Middle East and Africa and expects additional market registrations to be facilitated by an anticipated EMA license.  

Also, the French National Agency for Medicines and Health Products Safety (ANSM) granted an Autorisation Temporaire d'Utilisation de cohorte (ATU cohort), or Temporary Authorization for Use to allow access and reimbursement of vosoritide to begin immediately under an authorized process. An ATU allows access to drugs not yet approved in France, when provided for rare diseases, with no alternative options, and when the benefit/risk is presumed positive.

"The positive opinion from the CHMP represents a significant step towards making vosoritide available as a treatment choice for families.  The CHMP opinion reinforces the strength of the data and the clinical benefit to children as young as two years old.  The temporary authorization granted by the French health authority is a response to the urgency to treat these children," said Hank Fuchs, M.D., president Worldwide Research and Development at BioMarin. "We are committed to the scientifically robust, and rigorous study of vosoritide to continue to demonstrate the safety and efficacy of this investigational therapy that addresses the root cause of achondroplasia.  We are committed to providing information to treating physicians and families to determine if a treatment choice is right for them.  We are grateful to the patient advocacy groups, our clinical investigators and the children and their families for their participation in this clinical programme."

"This positive CHMP opinion represents a significant step toward delivering on the promise of the first pharmacological treatment option for children and families affected by achondroplasia.  As a treating physician, I see an urgent demand from families for a treatment option that addresses bone growth," said Klaus Mohnike, Professor of Paediatrics at Magdeburg University Hospital in Germany and investigator for the vosoritide clinical program.  "The depth and breadth of the data that supports this opinion builds upon a strong scientific foundation that will continue to increase our understanding of the potential impact of vosoritide on the medical complications that may result from achondroplasia."  

"Currently, there is a significant unmet need in achondroplasia. Further research is needed to address serious health complications beyond disproportionate short stature.  People with achondroplasia can experience foramen magnum compression, sleep apnea, and spinal stenosis," said Carmen Alonso Alvarez, managing director of Fundacion ALPE Foundation.  "We commend everyone involved in this effort to bring the potential first medicine to treat children with achondroplasia, which offers the possibility to expand treatment options beyond surgical intervention, address an unmet medical need, and advance the standard of care for our community."

The CHMP based its opinion on the totality of data from the vosoritide clinical development program including the outcomes from the randomized, double-blind, placebo-controlled phase 3 study evaluating the efficacy and safety of vosoritide.  The phase 3 Study was further supported by the ongoing long-term safety and efficacy from the phase 2 dose-finding study, which showed that growth rates have been sustained above participants' baseline rates and above the expected annualized growth velocity for untreated children with achondroplasia throughout the five year observation period for which data are currently available.  No acceleration of bone age was observed, suggesting that vosoritide is not reducing the total duration of the growth period. The data package included results from an ongoing phase 2 randomized double-blind study in infants and young children, including extensive pharmacokinetic and biomarker data, as well as preliminary growth data from participants in the 2 to 5 year age cohort.  Data in sentinel study participants showed a positive effect on growth following two years of vosoritide treatment in subjects aged 2 to 5 years. In addition, the data package included the phase 3 extension study and extensive natural history data.

The CHMP is a scientific committee composed of representatives from the 27-member states of the EU, and Iceland, Norway and Liechtenstein. The committee reviews medical product applications on their scientific and clinical merit and provides advice to the European Commission (EC), which has the authority to approve medicines for the EU.

Vosoritide, administered in approximately 38,000 injections, was generally well tolerated at all doses.  The majority of adverse events (AEs) were mild and no serious adverse events (SAEs) were reported as study drug related. Across all doses, injection site reactions and hypotension were the most common drug-related AEs.  All injection site reaction events were transient. AEs of hypotension were mild and transient with majority being asymptomatic and reported in the context of routine blood pressure measurements with minimal clinical impact. No new safety findings were observed.  There were no AEs related to disproportionate bone growth or bone pathology.  There has been no evidence of accelerated bone age (as assessed by radiologists blinded to the age of the subjects) or negative changes in bone mineral density.

Achondroplasia, the most common form of skeletal dysplasia leading to disproportionate short stature in humans, is characterized by slowing of endochondral ossification, which results in disproportionate short stature and disordered architecture in the long bones, spine, face and base of the skull. This condition is caused by a change in the fibroblast growth factor receptor 3 gene (FGFR3), a negative regulator of bone growth. Beyond disproportionate short stature, people with achondroplasia can experience serious health complications, including foramen magnum compression, sleep apnea, bowed legs, mid-face hypoplasia, permanent sway of the lower back, spinal stenosis and recurrent ear infections. Some of these complications can result in the need for invasive surgeries such as spinal cord decompression and straightening of bowed legs. In addition, studies show increased mortality at every age.