Scientists at the U.S. Food and Drug Administration found no concerns in the data submitted by Celltrion Pharm Inc. to support the approval of its biosimilar version of Roche Holding AG's non–Hodgkin lymphoma drug Rituxan, according to documents posted on the agency's website.
Biosimilars are intended to be lower-cost versions of biologic therapies — drugs derived from natural sources, such as microorganisms or plant or animal cells.
The FDA has approved 12 biosimilars since 2015, though only four of those products are currently being sold in the U.S., mostly due to ongoing patent litigation or agreements to postpone market entrance. The first biosimilar approved in the U.S. was Novartis AG's Zarxio, a version of Amgen Inc.'s Neupogen, which is used to treat a lack of white blood cells in cancer patients.
In April 2016, Incheon, Korea-based Celltrion and its partner Pfizer Inc. won approval of the second biosimilar in the U.S., Inflectra — a version of Johnson & Johnson's arthritis drug Remicade. Celltrion has also received approval of a Remicade biosimilar in Europe, where it is marketed as Remsima.
Celltrion entered into an exclusive partnership with Teva Pharmaceutical Industries Ltd in October 2016 to commercialize the Rituxan biosimilar in the U.S. and Canada, if approved.
Rituxan was first approved by the FDA in 1997 and has been used worldwide to treat over 4.4 million patients with B-cell malignancies and chronic inflammatory conditions, Celltrion noted in separate documents posted on the FDA's website.
Roche reported 2017 U.S. sales of Rituxan at $4.41 billion, though sales of the product in Europe, where it is sold under the brand name MabThera, were down by about 11% because of biosimilar competition.
According to guidelines from the National Comprehensive Cancer Network, treatment with Rituxan as a monotherapy or in combination with chemotherapy is the standard of care for patients with B-cell malignancies.
FDA review
In their review of Celltrion's application for its Rituxan biosimilar, currently known as CT-P10, the FDA's scientists said the analytical data supported the determination that the product was highly similar to Roche's brand-name drug, notwithstanding minor differences in clinically inactive components.
Although some analytical differences were observed between CT-P10 and the analyzed lots of Rituxan, supportive studies and justifications provided by Celltrion adequately addressed these differences, the FDA reviewers said.
Overall, they found no clinically meaningful differences between CT-P10 and the branded version of Rituxan in safety, purity and potency.
Before the FDA makes a decision on whether to allow Celltrion to market CT-P10, the agency wants its Oncologic Drugs Advisory Committee to weigh in on the company's application at an Oct. 10 public meeting. The committee will vote on whether the evidence is sufficient to support approval of the biosimilar as a treatment for adults with various forms of non–Hodgkin lymphoma.
Celltrion initially submitted an application to the FDA for its Rituxan biosimilar on April 28, 2017, but the agency rejected it in February, citing clinical, product quality and facility deficiencies.
From a clinical and statistical perspective, there were concerns that the safety and efficacy results of Celltrion's clinical study of the product may not have provided support of a demonstration of no clinically meaningful differences between CT-P10 and the brand-name product for the targeted oncology population, the FDA said in its briefing documents.
Celltrion resubmitted its application in late May with additional long-term efficacy and safety data, which the company said were generated after the initial submission. It also submitted new clinical data from a separate study.
"We are fully committed to preparing for this advisory committee meeting and look forward to the discussion about CT-P10," said Celltrion CEO Woosung Kee said in a Sept. 12 statement.