Amgen and Allergan have won the first U.S. approval for a biosimilar cancer treatment following FDA authorization of their Mvasi™ (bevacizumab-awwb), a near-copy of Roche subsidiary Genentech’s Avastin® (bevacisumab).
Mvasi has been approved for adults with five types of cancer, including in combination with chemotherapy for non-squamous non-small-cell lung cancer (NSCLC), in combination with chemotherapy for metastatic colorectal cancer (mCRC), glioblastoma, metastatic renal cell carcinoma in combination with interferon alfa, and in combination with chemotherapy for persistent, recurrent, or metastatic carcinoma of the cervix.
Just when Mvasi will reach the market and how much it will cost patients remain unknown.
Avastin retains U.S. patent exclusivity until 2019 and European patent exclusivity until 2022. Those patents have already been at the center of a legal wrangle between Amgen and Genentech earlier this year, and the dispute may flare up again before the first prescription is dispensed.
“It has been common lately for these biosimilars to be approved but not actually launch because the companies are still fighting them in court,” Brad Loncar, CEO of Loncar Investments, told GEN.
Amgen stated yesterday it is not discussing a launch date for Mvasi or its pricing while it remains in the process of providing application and manufacturing information to Genentech, as required by the Biologics Price Competition and Innovation Act (BPCIA).
“The patent information exchange under the regulatory scheme governing biosimilars (the BPCIA) is ongoing,” Amgen added in a statement.
In February, Genentech sued Amgen, contending that Amgen had failed to provide it with all the information it sought—information that would set the stage for both companies to decide on patents to be resolved through both immediate and long-term litigation. A federal judge dismissed Genentech’s complaint “without prejudice,” allowing it to refile its complaint within 45 days.
Roche did not do so, pending the U.S. Supreme Court deciding a separate dispute between Amgen and Novartis’ Sandoz unit, in which a unanimous High Court on June 12 sided with biosimilars developers by ruling that they can bring their treatments to market upon FDA approval without waiting an additional six months.
Competition, Pricing Concerns
Genentech spokeswoman Meghan Cox told GEN the company will not discuss how it will proceed in its dispute with Amgen: “We do not comment on ongoing litigation.
“We have long-supported the FDA’s efforts to implement a science-based pathway for the approval of biosimilars. Patients’ interests have always been front and center for us, and we believe having more treatment options is a good thing for patients,” Cox said. “Our focus continues to be on discovering the next wave of innovative treatments for people with serious diseases who need new options.”
Mvasi would add to the competition Genentech and parent Roche already face that has already begun cutting into sales of blockbusters that include Avastin. At CHF 6.783 billion ($7.08 billion), sales of Avastin last year were flat compared to 2015, with sales dipping 1% in the first half of this year, to CHF 3.405 billion ($3.55 billion). Roche is relying on sales overseas, especially China, to make up for a decline in the U.S. it blames “largely due to growing use of cancer immunotherapy medicines in lung cancer.”
Amgen, by contrast, has built a biosimilar portfolio that has grown to 10 programs. That portfolio includes four oncology biosimilars being co-developed with Allergan. The companies in July submitted a Biologics License Application seeking FDA approval for the second of those four, ABP 980, a biosimilar of Herceptin® (trastuzumab).
Mvasi is the second Amgen biosimilar to win FDA approval; the first came in September 2016, when the agency authorized the company’s Amjevita™ (adalimumab-atto), a near-copy of AbbVie’s multiindication blockbuster drug Humira® (adalimumab).
Amgen’s biosimilar pipeline includes versions of Genentech/Biogen-marketed Rituxan® (rituximab) called ABP 798; Johnson & Johnson’s Janssen Biotech-marketed Remicade® (infliximab) called ABP 710; Eli Lilly-marketed Erbitux® (cetuximab) called ABP 494; and three biosimilar programs for undisclosed products.
Mvasi is the seventh biosimilar to be approved by the FDA, which expressed the hope that its action would lower the sky-high prices of new cancer treatments.
“Bringing new biosimilars to patients, especially for diseases where the cost of existing treatments can be high, is an important way to help spur competition that can lower healthcare costs and increase access to important therapies,” FDA Commissioner Scott Gottlieb, M.D., said Thursday in a statement. “We’ll continue to work hard to ensure that biosimilar medications are brought to the market quickly, through a process that makes certain that these new medicines meet the FDA’s rigorous gold standard for safety and effectiveness.”
The prospect of lower prices, however, will likely have to await the launch of competitors to Mvasi, Loncar observed. Several are in Phase III development, including Biocad’s BCD-021, Biocon’s Biosimilar bevacizumab; Boehringer Ingelheim’s BI695502; IBC Generium/Affitech’s GNR-011 (Phase II/III); Kyowa Hakko Kirin’s FKB238; Pfizer’s PF-06439535; and Samsung Bioepis’ SB8.
‘A First Step’
“The history of generics is that it usually takes more than one competitor to have a major impact on price and that will even be more so for biosimilars since they are complicated to make and will have higher prices to begin with,” Loncar said. “Therefore, I don’t think you will see immediate changes to the cancer space because of this but it is a first step in an important long-term trend.”
The FDA approved Mvasi for indications that include:
- Metastatic colorectal cancer, in combination with intravenous 5-fluorouracil-based chemotherapy for first- or second-line treatment. Mvasi is not indicated for the adjuvant treatment of surgically resected colorectal cancer.
- Metastatic colorectal cancer, in combination with fluoropyrimidine–irinotecan- or fluoropyrmidine–oxaliplatin-based chemotherapy for the second-line treatment of patients who have progressed on a first-line bevacizumab product-containing regimen. Mvasi is not indicated for the adjuvant treatment of surgically resected colorectal cancer.
- NSCLC, in combination with carboplatin and paclitaxel for first-line treatment of unresectable, locally advanced, recurrent, or metastatic disease.
- Glioblastoma with progressive disease following prior therapy, based on improvement in objective response rate. No data is available demonstrating improvement in disease-related symptoms or survival with bevacizumab products.
- Metastatic renal cell carcinoma, in combination with interferon alfa.
- Cervical cancer that is persistent, recurrent, or metastatic, in combination with paclitaxel and cisplatin or paclitaxel and topotecan.
The FDA said it approved Mvasi as a biosimilar, but not an interchangeable product, based on extensive structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data, and other clinical safety and effectiveness data.
As with Avastin, Mvasi will be sold with a Boxed Warning about increased risk of gastrointestinal perforations; surgery and wound healing complications; and severe or fatal pulmonary, gastrointestinal, central nervous system, and vaginal hemorrhage.
According to the warning, patients should stop using Mvasi if gastrointestinal perforation or wound dehiscence occurs, and should not take Mvasi 28 days prior to and after elective surgery, and until the surgical wound is fully healed. Mvasi should not be given to patients with severe hemorrhage or in patients who cough up blood.
Mvasi is also associated with common expected side effects that include epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, and exfoliative dermatitis, the FDA said.
Avastin has been marketed in the U.S. since the FDA approved the drug in 2004.
“Avastin is obviously a very widely used drug in oncology so, yes, I do think we will look back on this as a meaningful approval,” Loncar added.