Marketing Authorization Based on Global Development Program Showing MVASI is Highly Similar to Avastin® (Bevacizumab)
First Biosimilar Bevacizumab Approved in the European Union
THOUSAND OAKS, Calif., Jan. 18, 2018 /PRNewswire/ — Amgen (NASDAQ: AMGN) and Allergan plc. (NYSE: AGN) today announced that the European Commission (EC) has granted marketing authorization for MVASI® (biosimilar bevacizumab). MVASI is the first biosimilar bevacizumab approved by the EC and is approved for the treatment of certain types of cancers, including in combination with fluoropyrimidine-based chemotherapy for metastatic carcinoma of the colon or rectum; in combination with paclitaxel for metastatic breast cancer; in combination with platinum-based chemotherapy for unresectable advanced, metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC); in combination with erlotinib for unresectable advanced, metastatic or recurrent non-squamous NSCLC; in combination with interferon alfa-2a for advanced and/or metastatic renal cell cancer; in combination with carboplatin and paclitaxel, carboplatin and gemcitabine, and paclitaxel, topotecan, or pegylated liposomal doxorubicin for advanced, platinum-sensitive, or platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer; and in combination with paclitaxel and cisplatin, or alternatively, paclitaxel and topotecan for persistent, recurrent, or metastatic carcinoma of the cervix.
Amgen and Allergan are committed to developing high-quality biosimilars with a robust analytic and clinical package. The EC approved MVASI based on a comprehensive data package that demonstrated MVASI and bevacizumab are highly similar, with no clinically meaningful differences in terms of the efficacy, safety and immunogenicity between the products. Clinical studies included results from a Phase 3 trial in patients with non-squamous NSCLC.
"MVASI is the first product from our collaboration with Amgen to receive marketing authorization from the European Commission, highlighting the success of our joint commitment to developing cancer biosimilars," said David Nicholson, chief research and development officer at Allergan. "We look forward to our continued work with Amgen and to providing important medicines to patients in the future."
Approval from the EC grants a centralized marketing authorization with unified labeling in the 28 countries that are members of the European Union (EU). Norway, Iceland and Liechtenstein, as members of the European Economic Area, will take corresponding decisions on the basis of the decision of the EC.
In September 2017, MVASI became the first anti-cancer biosimilar, as well as the first biosimilar bevacizumab, to be approved by the U.S. Food and Drug Administration (FDA). Amgen and Allergan are collaborating on the development and commercialization of four oncology biosimilars. Amgen has a total of 10 biosimilars in its portfolio, two of which have been approved by the EC.
About MVASI® (biosimilar bevacizumab) in the EU
MVASI is a biosimilar to bevacizumab, a recombinant immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to vascular endothelial growth factor (VEGF) and inhibits the interaction of VEGF with its receptors, VEGF receptor-1 and VEGF receptor-2, thus inhibiting establishment of new blood vessels necessary for the maintenance and growth of solid tumors.
MVASI, in combination with fluoropyrimidine-based chemotherapy, is indicated for treatment of adult patients with metastatic carcinoma of the colon or rectum.
MVASI, in combination with paclitaxel, is indicated for first-line treatment of adult patients with metastatic breast cancer.
MVASI, in addition to platinum-based chemotherapy, is indicated for first-line treatment of adult patients with unresectable advanced, metastatic or recurrent NSCLC other than predominantly squamous cell histology.
MVASI, in combination with erlotinib, is indicated for first-line treatment of adult patients with unresectable advanced, metastatic or recurrent non-squamous NSCLC with Epidermal Growth Factor Receptor (EGFR) activating mutations.
MVASI, in combination with interferon alfa-2a, is indicated for first-line treatment of adult patients with advanced and/or metastatic renal cell cancer.
MVASI, in combination with carboplatin and paclitaxel, is indicated for the front-line treatment of adult patients with advanced (International Federation of Gynecology and Obstetrics (FIGO) stages IIIB, IIIC and IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer.
MVASI, in combination with carboplatin and gemcitabine or in combination with carboplatin and paclitaxel, is indicated for treatment of adult patients with first recurrence of platinum-sensitive epithelial ovarian, fallopian tube or primary peritoneal cancer who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor-targeted agents.
MVASI, in combination with paclitaxel, topotecan, or pegylated liposomal doxorubicin, is indicated for the treatment of adult patients with platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who received no more than two prior chemotherapy regimens and who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor-targeted agents.
MVASI, in combination with paclitaxel and cisplatin or, alternatively, paclitaxel and topotecan in patients who cannot receive platinum therapy, is indicated for the treatment of adult patients with persistent, recurrent, or metastatic carcinoma of the cervix.
MVASI EU Important Safety Information
The EU Summary of Product Characteristics for MVASI lists the following Special Warnings and Precautions: gastrointestinal (GI) perforations and fistulae, GI-vaginal fistulae in study GOG-0240, non-GI fistulae, wound healing complications, hypertension, posterior reversible encephalopathy syndrome (PRES), proteinuria, arterial thromboembolism, venous thromboembolism, haemorrhage, pulmonary haemorrhage/haemoptysis, congestive heart failure (CHF), neutropenia and infections, hypersensitivity reactions/infusion reactions, osteonecrosis of the jaw (ONJ), intravitreal use, eye disorders, systemic effects following intravitreal use, and ovarian failure/fertility.
About MVASI™ (bevacizumab-awwb) in the U.S.
MVASI is a biosimilar to bevacizumab, a recombinant IgG1 mAb that binds to VEGF and inhibits the interaction of VEGF with its receptors, VEGF receptor-1 and VEGF receptor-2, thus inhibiting establishment of new blood vessels necessary for the maintenance and growth of solid tumors.
MVASI is indicated for the treatment of metastatic colorectal cancer (mCRC), with intravenous 5-fluorouracil–based chemotherapy for first- or second-line treatment.
MVASI is indicated for the treatment of mCRC, with fluoropyrimidine- irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for second-line treatment in patients who have progressed on a first-line bevacizumab-containing regimen. MVASI is not indicated for adjuvant treatment of colon cancer.
MVASI is indicated for the treatment of non-squamous NSCLC, with carboplatin and paclitaxel for first line treatment of unresectable, locally advanced, recurrent or metastatic disease.
MVASI is indicated for the treatment of glioblastoma, as a single agent for adult patients with progressive disease following prior therapy.
The effectiveness of bevacizumab products in glioblastoma is based on an improvement in objective response rate. There are no data demonstrating an improvement in disease-related symptoms or increased survival with bevacizumab products.
MVASI is indicated for the treatment of metastatic renal cell carcinoma with interferon alfa.
MVASI is indicated for the treatment of cervical cancer, in combination with paclitaxel and cisplatin or paclitaxel and topotecan in persistent, recurrent, or metastatic disease.
MVASI is currently not available commercially. This is not an offer for sale. The following information is derived from the approved label in the U.S.
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MVASI U.S. Important Safety Information
Boxed WARNINGS
Gastrointestinal (GI) Perforations
The incidence of gastrointestinal perforation, some fatal, in bevacizumab product-treated patients ranges from 0.3-3.2%. Fatal outcome was reported in <1% of bevacizumab-treated patients. Discontinue MVASI in patients with gastrointestinal perforation.
Surgery and Wound Healing Complications
The incidence of wound healing and surgical complications, including serious and fatal complications, is increased in bevacizumab product-treated patients. Discontinue MVASI in patients with wound dehiscence. The appropriate interval between termination of bevacizumab products and subsequent elective surgery required to reduce the risks of impaired wound healing/wound dehiscence has not been determined. Discontinue at least 28 days prior to elective surgery. Do not initiate MVASI for at least 28 days after surgery and until the surgical wound is fully healed.
Hemorrhage
Severe or fatal hemorrhage, including hemoptysis, gastrointestinal bleeding, central nervous system hemorrhage, epistaxis, and vaginal bleeding occur up to 5-fold more frequently in patients receiving bevacizumab products. Across indications, the incidence of grade ≥3 hemorrhagic events among patients receiving bevacizumab ranged from 0.4% to 6.9%. Do not administer MVASI to patients with serious hemorrhage or recent hemoptysis (≥1/2 tsp of red blood). Discontinue MVASI in patients with serious hemorrhage (ie, requiring medical intervention).
Additional serious adverse events
- Additional serious and sometimes fatal adverse events with increased incidence in the bevacizumab product-treated arm vs control included
- GI fistulae (up to 2% in metastatic colorectal cancer)
- Non-GI fistulae (<1% in trials across various indications; 1.8% in a cervical cancer trial)
- Arterial thromboembolic events (grade ≥3, 2.6%)
- Proteinuria (nephrotic syndrome, <1%)
- Additional serious adverse events with increased incidence in the bevacizumab product-treated arm vs control included
- GI-vaginal fistulae occurred in 8.3% of patients in a cervical cancer trial
- Venous thromboembolism (grade 3-4, up to 10.6%) in patients with persistent, recurrent, or metastatic cervical cancer treated with chemotherapy and bevacizumab product
- Hypertension (grade 3-4, 5%-18%)
- Posterior reversible encephalopathy syndrome (PRES) (<0.5%)
- Infusion reactions with the first dose of bevacizumab product-treated patients were uncommon (<3%), and severe reactions occurred in 0.2% of patients
- Inform females of reproductive potential of the risk of ovarian failure prior to starting treatment with MVASI
Pregnancy warning
- Based on the mechanism of action and animal studies, bevacizumab products may cause fetal harm
- Advise female patients that MVASI may cause fetal harm, and to inform their healthcare provider of a known or suspected pregnancy
- Advise females of reproductive potential to use effective contraception during treatment with MVASI and for 6 months after the last dose of MVASI
- Advise nursing women that breastfeeding is not recommended during treatment with MVASI
- MVASI may impair fertility
Most Common Adverse Events
- Across indications, the most common adverse reactions observed in bevacizumab product-treated patients at a rate of >10% and at least twice the control arm rate were: epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, exfoliative dermatitis
- Across all studies, bevacizumab product was discontinued in 8.4% to 21% of patients because of adverse reactions.
Please see full Prescribing Information, including Boxed WARNINGS, at www.Amgen.com.
About the Amgen and Allergan Collaboration
In December 2011, Amgen and Allergan plc. (then Watson Pharmaceuticals, Inc.) formed a collaboration to develop and commercialize, on a worldwide basis, four oncology antibody biosimilar medicines. This collaboration reflects the shared belief that the development and commercialization of biosimilar products will not follow a pure brand or generic model, and will require significant expertise, infrastructure, and investment to ensure safe, reliably supplied therapies for patients. Under the terms of the agreement, Amgen will assume primary responsibility for developing, manufacturing and initially commercializing the oncology antibody products.
About Amgen Biosimilars
Amgen Biosimilars is committed to building upon Amgen's experience in the development and manufacturing of innovative human therapeutics to expand Amgen's reach to patients with serious illnesses. Biosimilars will help to maintain Amgen's commitment to connect patients with vital medicines, and Amgen is well positioned to leverage its more than 35 years of experience in biotechnology to create high quality biosimilars and reliably supply them to patients worldwide.
For more information, visit http://www.amgenbiosimilars.com and follow us on http://www.twitter.com/amgenbiosim.
About Amgen's Commitment to Oncology
Amgen Oncology is committed to helping patients take on some of the toughest cancers, such as those that have been resistant to drugs, those that progress rapidly through the body and those where limited treatment options exist. Amgen's supportive care treatments help patients combat certain side effects of strong chemotherapy, and our targeted medicines and immunotherapies focus on more than a dozen different malignancies, ranging from blood cancers to solid tumors. With decades of experience providing therapies for cancer patients, Amgen continues to grow its portfolio of innovative and biosimilar oncology medicines.
About Allergan plc
Allergan plc (NYSE: AGN), headquartered in Dublin, Ireland, is a bold, global pharmaceutical company and a leader in a new industry model – Growth Pharma. Allergan is focused on developing, manufacturing and commercializing branded pharmaceuticals, devices and biologic products for patients around the world.
Allergan markets a portfolio of leading brands and best-in-class products for the central nervous system, eye care, medical aesthetics and dermatology, gastroenterology, women's health, urology and anti-infective therapeutic categories.
Allergan is an industry leader in Open Science, the Company's R&D model, which defines our approach to identifying and developing game-changing ideas and innovation for better patient care. This approach has led to Allergan building one of the broadest development pipelines in the pharmaceutical industry with 70+ mid-to-late stage pipeline programs in development.
Our Company's success is powered by our more than 16,000 global colleagues' commitment to being Bold for Life. Together, we build bridges, power ideas, act fast and drive results for our customers and patients around the world by always doing what is right.
With commercial operations in approximately 100 countries, Allergan is committed to working with physicians, healthcare providers and patients to deliver innovative and meaningful treatments that help people around the world live longer, healthier lives every day.
For more information, visit Allergan's website at www.Allergan.com.
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Avastin® is registered trademark of Genentech.
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