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CHMP Backs the First Biosimilar MAb from Hospira and Celltrion

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By Jennifer Boggs
Managing Editor

Almost exactly a year after Remsima (infliximab) won approval in Korea as the first ever biosimilar monoclonal antibody (MAb), the Remicade copycat drug won a positive opinion from Europe's Committee for Medicinal Products for Human Use (CHMP), clearing the way for formal European approval within the next three months.

Shares of Hospira Inc. (NYSE:HSP), which is expected to market the drug in Europe as Inflectra – partner Korean biotech Celltrion Inc. gained a CHMP recommendation to sell the drug as Remsima – gained $2.16 Friday to close at $38.31.

Unlike in the U.S., where regulators continue to hash out biosimilar guidelines, the biosimilar pathway in Europe is more established, with more than a dozen products having hit the market since the first biosimilar, recombinant growth hormone omnitrope somatropin from Novartis AG's Sandoz unit, gained approval in 2006. Still, Inflectra and Remsima mark the first biosimilar versions of MAbs, by far much larger and more complex to copy when compared to proteins such as growth hormone and erythropoietin (EPO). (See BioWorld Today, June 20, 2013.)

The good news for Hospira and Celltrion is that the CHMP recommended broad labels for Inflectra/Remsima, despite pivotal data from only one or two indications. Hospira had tested its autoimmune biosimilar in rheumatoid arthritis (RA), where it demonstrated equivalence to Remicade (Johnson & Johnson), with 73.4 percent of patients receiving Inflectra hitting the ACR20 endpoint vs. 69.7 percent in the Remicade arm. Celltrion said it tested Remsima in 874 patients with ankylosing spondylitis and RA across Phase I and Phase III trials, which results demonstrating clinical comparability to Remicade in terms of both safety and efficacy.

The CHMP's recommendation, however, covers other Remicade indications, including RA and ankylosing spondylitis, along with adult and pediatric Crohn's disease, ulcerative colitis, psoriatic arthritis and psoriasis.

"We view this as a positive as pivotal trials were not conducted for all Remicade's indications, particularly the gastrointestinal indications," RBC Capital Markets analyst Shibani Malhotra wrote in a research report.

Lake Forest, Ill.-based Hospira is waiting for official European Commission approval before disclosing specific launch plans. But "we're hoping it will improve access for patients to this really important product," said Hospira spokesman Dan Rosenberg.

Like its reference product, Inflectra targets tumor necrosis factor-alpha, which has been linked to a number of autoimmune diseases. Remicade, which is estimated to cost from $19,000 to $22,000 per year per patient, recorded European sales of more than $2 billion in 2012.

"It's too early to speculate on pricing" for Inflectra, Rosenberg told BioWorld Today, though he said the cost of Hospira's biosimilar naturally will be lower than Remicade's.

Assuming final approval from the European Commission – usually a rubber stamp to the CHMP's recommendation – Inflectra will be Hospira's third marketed biosimilar in the European market.

The firm already sells Retacrit, an EPO biosimilar for treating anemia associated with chronic renal failure and in patients receiving chemotherapy for solid tumors, which was approved in 2008. And, in 2011, it gained approval of Nivestim, a biosimilar version of filgrastim for use in neutropenia.

How well the drugs have done, however, is tough to gauge. The company does not break out specific sales of its biosimilar products in its quarterly earnings reports.

Education Key to Biosimilars Uptake

Small-molecule drugs that go off patent are quickly displaced in the market by cheaper generics. But that same rapid uptake hasn't been true of copycat biologics. The complexity of biologic drugs – due in part to the fact that manufacturing processes are part of companies' proprietary information – means that it's difficult to make an exact copy, thereby limiting the automatic substitution of a biosimilar for a reference product.

A report presented at the BIO International Convention in Chicago earlier this year pointed to several reasons for the slow adoption in Europe, including the still-high costs of the drugs compared to small-molecule generics and confusion about whether similarity warranted interchangeability. EPO biosimilars, for example, had managed to nab only a 12 percent share of the overall EPO market by mid-2011. (See BioWorld Today, April 30, 2013.)

The Project Group on Market Access and Uptake of Biosimilars also noted a clear lack of understanding of biosimilars by the medical community.

RBC's Malhotra said he will watch market uptake of Hospira's Inflectra closely. Despite Inflectra's broad approval, some pediatric indications will be delayed, thanks to J&J's patent extension to 2015, and Malhotra noted that the New Brunswick, N.J.-based big pharma firm could respond to the biosimilar threat by cutting the price of Remicade in Europe. So it "will likely take time before we get a clearer view of the uptake," he wrote.

Malhotra also expects Hospira to "educate doctors and gain reimbursement, particularly in the extrapolated [gastrointestinal] indications where there is no clinical work."

Rosenberg said that is the plan. Once official approval is granted, he said Hospira would begin reaching out to physicians to describe the benefits of the Remicade biosimilar. "We know that providing clear information" about Inflectra to the medical community "will be critical."

Manufacturing issues that have plagued Hospira of late – the company has received four warning letters in the past year or so – are not expected to affect Inflectra's launch. Rosenberg said the issues, which the company is working to resolve at its Rocky Mount, N.C., facility, have "nothing to do" with Inflectra's production.

Hospira obtained rights to the product from Celltrion for development and marketing in Europe, the U.S., Canada, Australia and New Zealand. The drug is part of an eight-product deal between the companies, which also includes a biosimilar version of breast cancer drug Herceptin (trastuzumab, Roche AG).

Hospira also continues to pursue a U.S. biosimilars strategy. The company is in Phase III studies with its EPO biosimilar.

"We continue to enroll patients and expect to make our first submissions in late 2014 or early 2015," Rosenberg pointed out.

Editor's note: For a copy of BioWorld Data's newest report, The Biosimilars Game: A Scorecard for Opportunities, Threats, and Clinical Strategies, contact account managers for exclusive introductory pricing at (800) 477-6307.