Hospira’s Inflectra, EU’s First Biosimilar mAb, Will Challenge Skeptics

Hospira’s Inflectra becomes the first biosimilar monoclonal antibody to be authorized in Europe – but pricing and overcoming doctors’ skepticism looks like the key to real EU success.

Hospira Inc.’s Inflectra (infliximab), the first biosimilar monoclonal antibody to be approved in the EU, may face an uphill battle to convince EU health care professionals and patients in many member states of its value, particularly given the skepticism in Europe surrounding biosimilars in general.

The European Commission gave the nod to Inflectra on Sept. 10, thereby putting flesh on the bones of the European Medicines Agency’s recommendation of June 28 (Also see "Hospira, Korea’s Celltrion Get EU Nod For First Monoclonal Antibody Biosimilar" - Pink Sheet, 1 Jul, 2013.). Unsurprisingly, the EMA issued a positive recommendation for Remsima (infliximab), manufactured by Korea’s Celltrion Inc. “Inflectra is Remsima from Celltrion, also licensed to Egis Pharmaceuticals PLC for Eastern Europe,” said Alan Sheppard, Global Head Generics at IMS Health Inc. Both are biosimilar versions of Johnson & Johnson‘s blockbuster tumor necrosis factor inhibitor Remicade (infliximab).

“Importantly, the EMA opinion and EC ratification were aligned on the approval of Inflectra across all indications of the reference product. At the same time, they were consistent in their agreement to approve the same INN [International Nonproprietary Name] as the reference,” a spokesperson for Hospira confirmed.

Pricing Is Key

Like Remicade, Inflectra – and undoubtedly Remsima, when the Commission formally approves it – is indicated for a wide variety of conditions in the EU. Its main income will be generated from the treatment of rheumatoid arthritis, but the EU Commission’s authorization also covers ankylosing spondylitis, Crohn’s disease, ulcerative colitis, psoriasis and psoriatic arthritis.

J&J’s Remicade recorded European sales of over $2 billion in 2012 – global sales were $6.1 billion – making an attractive target for those embarking on the biosimilar mAbs trail. In Europe, J&J splits profits 50/50 on Remicade with Merck & Co. Inc. Launches in Europe will be staggered through early 2015, as Remicade loses exclusivity at different times in different countries, Celltrion and Hospira said.

The real question is how much of this market the biosimilars really will be able to acquire and how they must be priced to stand a real chance of gaining a share.

Firstly, Hospira and Celltrion are not the only companies eyeing up Remicade. U.S.-based Epirus Biopharmaceuticals said on Aug. 28 that its own biosimilar infliximab had demonstrated “clinical comparability” to Remicade.

Pricing, therefore, will be a crucial factor, not only to attractiveness but also to securing a decent return on investment. But pricing could be complex, given it will be dependent on each country’s policy for biosimilars, said Sheppard. And if it follows earlier biosimilars, then a 50% price reduction would be likely and margins will be lower, as it has been in-licensed, he added.

Still, some industry observers say a price in the range of 30% might be a starting level. Sheppard suggested that Hospira might need to lower the price of Inflectra and “potentially” could lose all its new business if it doesn’t. “Remember, products cannot be substituted, so existing patients will stay on Remicade; it will be the new patient market that is open,” he pointed out.

Hospira itself would not be drawn on the price issue. “It’s difficult to predict pricing, as it varies by molecule and by market,” the spokesperson said.

The Next Challenge

If the U.S. manufacturer can make the price alluring, though, the next nut to crack will be convincing health care professionals and patients. Whereas experience to date suggests that countries such as the U.K. are rather accepting of biosimilars in general, the EU’s largest national drug market, Germany, is more skeptical.

The introduction of biosimilar mAbs in Europe is expected to deliver savings of up to €20.4 billion ($27 billion) by 2020, with the biggest savings predicted in France, Germany and the U.K., Hospira has said. Still, if companies are going to have to lower prices significantly, then breaking into Germany will be vital (Also see "Biosimilar Remicade Will Pit Rising Cost Pressures Against Prescriber Caution" - In Vivo, 15 May, 2013.).

It will be interesting to see if the statement of Stan Bukofzer, Corporate Vice President and Chief Medical Officer, Hospira, that “the rigorous scientific review and approval process by the EMA and EC confirms that Inflectra has demonstrated similar quality, efficacy and safety to Remicade,” resonates positively with Europe’s doctors.

Experience Will Help

The good news for Hospira, Celltrion and other biosimilar mAb manufacturers further down the line is that there is a wealth of experience to build upon. Hospira points out that it is the only U.S.-based company with biosimilars on the European market, including Retacrit (epoetin zeta) – which was launched in Europe in early 2008 – and Nivestim (filgrastim) – which reached the European market in 2010.

“In the nearly six years Hospira has been on the market in Europe, we’ve seen growing acceptance of biosimilars among clinicians and patients, and both the biosimilars we sell continue to see strong volume growth. We believe our experience in the market will help as we launch Inflectra, and we plan a broad educational campaign to ensure that clinicians prescribing infliximab learn about the benefits and safety of our product,” a spokesperson for the company said.

Other companies, such as Novartis AG’s generics subsidiary, Sandoz International GMBH, also are making a name for themselves in biosimilars. Sandoz is regarded as a pioneer in the field and the global market leader with over 50% share of all biosimilars approved in the highly regulated markets of the U.S., Canada, Europe, Japan and Australia.

In the EU, Sandoz markets a biosimilar version of Epogen under the name Binocrit (epoetin alfa), the growth hormone Omnitrope (somatropin), as well as a biosimilar version of Neupogen called Zarzio (filgrastim). All three Sandoz products occupy the number-one biosimilar position in their respective categories. Moreover, this past July, Sandoz began a global Phase III trial of its biosimilar version of Amgen Inc.’s Enbrel (etanercept) (Also see "Sandoz Biosimilar Strategy For Etanercept: Start Small, But Test Globally" - Pink Sheet, 22 Jul, 2013.).

It certainly will be interesting, price aside, to see what happens with the Inflectra’s foray into the world of EU reimbursement and health technology assessment. “Inflectra will have to go through the typical reimbursement process in each market. In some EU markets, this may require an HTA submission,” the spokesperson confirmed. This is no simple task, given the sheer variety of HTA processes within the 28-member European Union. Again, pricing will be crucial.

It, therefore, is extremely difficult to predict how this foray in the world of biosimilar mAbs will go. Humira and eventually Celltrion might have to be satisfied with being brave trailblazers in a relatively uncertain climate.