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Astellas Claims EU Okay For First Claudin 18.2 Cancer Drug
News
European Commission
The EU has followed Japan and GB in approving Astellas' first-to-market claudin 18.2-targeted therapy Vyloy, clearing it for gastric and gastroesophageal junction (GEJ) cancer.
Vyloy (zolbetuximab) has been given the go-ahead for use in combination with chemotherapy for the first-line treatment of adults with locally advanced or metastatic HER2-negative, claudin 18.2-positive gastric or GEJ adenocarcinoma that cannot be treated with surgery.
The European Commission's decision comes a few months after the FDA turned down Astellas' marketing application for zolbetuximab in the US because of "unresolved deficiencies" found during an inspection of a third-party manufacturing facility for the antibody. Astellas refiled its US application in May, and a decision is expected in November.
Claudin 18.2 is a biomarker positively expressed in approximately 38% of advanced gastric cancer tumours, according to Astellas.
In healthy gastric epithelium, the molecule is usually located within tight junctions that connect cells and isn't typically found in other tissues. After cancer develops, it can move to the surface of the cells' outer membranes, making it a useful target for drug treatment.
That's important because gastric cancer has seen little in the way of therapeutic innovation in recent decades, despite being the fourth deadliest cancer worldwide, killing around 770,000 people a year. It has a lamentable five-year relative survival rate of only around 6%.
In two pivotal trials – SPOTLIGHT and GLOW – Vyloy was shown to reduce the risk of disease progression or death, as well as overall survival (OS) when added to chemotherapy in treatment-naïve patients with this type of cancer, extending life by around two months compared to placebo plus chemo.
"Sadly, due to similar symptoms to more common stomach conditions, gastric and gastroesophageal junction cancers are often diagnosed at the advanced or metastatic stage when treatment options have traditionally been relatively limited," said Zorana Maravic, chief executive of patient organisation Digestive Cancers Europe (DiCE).
"Ensuring timely diagnosis, followed by personalised treatment and care, will be essential to better survival and quality of life for patients," she added.
Astellas acquired zolbetuximab with its takeover of Ganymed Pharma in 2016, paying around $430 million upfront in a deal with a total value of up to $1.3 billion.
Analysts have suggested that the drug could eventually make annual sales of $1 billion or more, with the caveat that achieving those levels will depend on widespread adoption of claudin 18.2 testing, which isn't routinely carried out.
With that in mind, Astellas could be helped by a host of other claudin 18.2-directed drugs that are coming through development, including Innovent Bio's IBI343 in phase 3, AstraZeneca/Keymed's AZD0901 in phase 2, and a string of earlier-stage candidates from Merck KGaA/Hengrui, Transcenta, I-Mab, BioNTech, Leap Therapeutics, and Legend Biotech, amongst others.
Astellas is also testing Vyloy in a mid-stage trial involving patients with claudin-18.2-positive pancreatic cancer, another group with very few treatment options.
EU Committee Recommends Approval Of AstraZeneca's Fasenra To Treat Eosinophilic Granulomatosis With Polyangiitis
AstraZeneca, global, science-led biopharmaceutical company, announced that its Fasenra (benralizumab) has been recommended for approval in the European Union (EU) as an add-on treatment for adult patients with relapsing or refractory eosinophilic granulomatosis with polyangiitis (EGPA). EGPA is a rare, immune-mediated vasculitis that can result in damage to multiple organs, and without treatment, can be fatal.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency based its positive opinion on results from the MANDARA phase III trial published in The New England Journal of Medicine, which compared the efficacy and safety of Fasenra to the only approved EGPA treatment, mepolizumab, in patients with relapsing or refractory EGPA. MANDARA was the first head-to-head non-inferiority trial of biologics in patients with EGPA. Patients were randomised to receive either a single 30 mg subcutaneous injection of Fasenra, or three separate 100 mg subcutaneous injections of mepolizumab every four weeks.
In the trial, nearly 60% of Fasenra-treated patients achieved remission which was comparable to mepolizumab-treated patients. Data also showed 41% of Fasenra-treated patients fully tapered off oral corticosteroids (OCS) (vs. 26% in the comparator arm (difference: 16%; 95% CI: 1,31)).
Bernhard Hellmich, Chair of the Department of Internal Medicine, Rheumatology, and Immunology at the Medius Klinik Kirchheim, Teaching Hospital of the University of Tübingen, Co-Director of the Vasculitis Center Tübingen-Kirchhei, and MANDARA Principal Investigator said: "People living with EGPA in Europe often face debilitating symptoms and suffer serious and long-lasting side effects from treatment with long-term oral corticosteroids. With its unique mechanism of action that leads to near complete depletion of eosinophils, Fasenra represents a much-needed potential treatment option for EGPA patients to help them achieve remission and taper off steroid therapy."
Ruud Dobber, executive vice president, BioPharmaceuticals Business Unit, AstraZeneca said: "With today's recommendation, the EGPA community in Europe is one step closer to accessing a new and convenient treatment option to alleviate some of the impact of this debilitating disease. With over 15 years of clinical data, Fasenra is a well-established, leading treatment for severe eosinophilic asthma, and now has the potential to transform care for patients with EGPA. Today's news demonstrates the potential of Fasenra to help patients suffering from eosinophilic diseases beyond severe asthma."
The safety and tolerability profile for Fasenra in the MANDARA trial was consistent with the known profile of the medicine.
Approximately half of patients with EGPA have adult-onset severe eosinophilic asthma (SEA) and often have sinus and nasal symptoms. If approved, Fasenra would be only the second biologic approved to treat this disease.
Fasenra was recently approved in the US for the treatment of EGPA9 and is also approved as an add-on maintenance treatment for severe eosinophilic asthma (SEA) in more than 80 countries including the US, Japan, EU and China. It is also approved in children and adolescents ages six and above in the US and Japan.
EGPA, formerly known as Churg-Strauss Syndrome, is a rare, immune-mediated inflammatory disease that is caused by inflammation of small to medium-sized blood vessels. It is estimated that 118,000 people throughout the world live with EGPA. EGPA can result in damage to multiple organs, including lungs, upper airway, skin, heart, gastrointestinal tract and nerves. The most common symptoms and signs include extreme fatigue, weight loss, muscle and joint pain, rashes, nerve pain, sinus and nasal symptoms, and shortness of breath. Without treatment, the disease may be fatal. Almost half (47%) of patients do not achieve remission with current treatments.
There are limited treatment options for EGPA. Patients are often treated with chronic high-dose OCS and experience recurrent relapses when attempting to taper off OCS.
MANDARA was a phase III, randomised, double-blinded, active-controlled trial, which compared the efficacy and safety of Fasenra to mepolizumab in adult patients with relapsing or refractory EGPA. In the trial, 140 patients were randomised 1:1 to receive either a single 30 mg subcutaneous injection of Fasenra or three separate 100 mg subcutaneous injections of the active comparator every four weeks.
The primary endpoint was the proportion of patients who were in remission at both weeks 36 and 48. Remission is defined as Birmingham Vasculitis Activity Score (BVAS)=0 and OCS dose less than or equal to 4 mg/day. A secondary endpoint was the proportion of patients who were able to fully taper off OCS at weeks 48 through 52. The primary statistical analysis was to demonstrate non-inferiority of Fasenra versus mepolizumab based on the primary endpoint.
Fasenra (benralizumab) is currently approved in more than 80 countries, including the US, EU, Japan, and China. Fasenra has been prescribed to over 130,000 patients globally.
Fasenra is in development for other diseases including chronic obstructive pulmonary disease, chronic rhinosinusitis with nasal polyps and hypereosinophilic syndrome.
Fasenra was developed by AstraZeneca and is in-licensed from BioWa, Inc., a wholly owned subsidiary of Kyowa Kirin Co., Ltd., Japan.
Respiratory & immunology, part of AstraZeneca BioPharmaceuticals, is a key disease area and growth driver to the company.
AstraZeneca is an established leader in respiratory care with a 50-year heritage and a growing portfolio of medicines in immune-mediated diseases. The company is committed to addressing the vast unmet needs of these chronic, often debilitating, diseases with a pipeline and portfolio of inhaled medicines, biologics and new modalities aimed at previously unreachable biologic targets. Its ambition is to deliver life-changing medicines that help eliminate COPD as a leading cause of death, eliminate asthma attacks and achieve clinical remission in immune-mediated diseases.
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in oncology, rare diseases, and biopharmaceuticals, including cardiovascular, renal & metabolism, and respiratory & immunology.
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