There has been a concerted push by regulators in the US to encourage the development of biosimilars, with the US Food and Drug Administration (FDA) last year unveiling its ‘action plan’ to encourage and reward development in the area.
From the outside, the US market for biosimilars seems to be steadily developing, with a greater number of biosimilar applications and approval rates seen in 2018, compared with previous years. However, there remain doubts about its short-term viability, which has led some larger companies to decrease investment in biosimilars and to cease development of certain candidates.
At the start of the year, Pfizer pulled financing away from its biosimilars unit away to cut away five candidates and pruned 150 jobs, and Novartis chose not pursue an application for a rituximab biosimilars due to the data requirements.
Celltrion Healthcare was one of the early developers of biosimilar technology, but that has not stopped it running into trouble bringing its products to market in the US. The company had previously told us that the FDA had requested contradictory information, and received a warning letter for its biosimilar production plant since resolved.
BioPharma-Reporter (BPR) contacted HoUng Kim (HK), head of the medical and marketing division at Celltrion Healthcare, to learn of the company’s experience of commercialising in Europe and the US, as well as how it sees the latter market developing.
BPR: How is Celltrion’s business across the US and EU markets developing?
HK: In Europe, Celltrion’s Remsima (infliximab) achieved 52% market share (based on vials) in Europe in the fourth quarter of 2017, which marked the first time a biosimilar has surpassed the market share of original drugs.
Truxima (rituximab) logged market shares of 76% and 66% in the Netherlands and Britain, respectively, on the back of plentiful clinical data in the third quarter of 2018.
As for Herzuma (trastuzumab), Celltrion Healthcare recently won big tenders in France. The total order volume accounts for some 40% of the country’s trastuzumab market, consisting of the original and copy versions.
In the US, through our partnership with Pfizer, the fourth-quarter sales of Remsima (infliximab), also known as Inflectra, in the US market increased to $70m, up 59% from a year ago. The company's annual earnings of Inflectra also stood at $259m, up 119% from 2017.
Although there have been barriers to biosimilar uptake in the US, there have been some proactive measures by the FDA to support biosimilars, such as the recent statement by the Health and Human Services (HSS) secretary, Alex Azar. To lower prescription drug costs by targeting backdoor rebates, there will be an opportunity to remove barriers to competition and to do more to demonstrate the value of biosimilars.
Also, with the recent HHS proposal to target rebates, biosimilar manufacturers will be able to gain favoured formulary tier placement and bring down drug costs by avoiding ‘rebate traps’ brand-name drug makers have been using to block patient access to more affordable options.
BPR: How do you expect biosimilar development and commercialisation to develop in the coming years?
HK: The competition between biosimilar developers is accelerating, as new entrants are competing against each other aggressively to capture market share. The improvement in production efficiency will be an essential factor in this battle of biosimilars.
One of the biggest barriers that Celltrion has witnessed to entering and promoting biosimilars was the originator companies’ rebate trap to incentivise payers to continue with originator drugs. This inhibits market competition and there has been a strong need to improve cost transparency to create price competition.
Biosimilar manufacturers should be able to offer competitive contracting terms to payers. Biosimilar would need to offer affordable prices to persuade payers that the cost savings from biosimilars are significant.
Even though biosimilars offer incredible health and economic benefits, these opportunities will not be fully realised. Significant challenges for biosimilars arise because all stakeholders involved – patients, physicians, payers, and biosimilar manufactures need to realise gains from the biosimilars and reach a consensus on using biosimilars.
BPR: What needs to happen for biosimilar market to continue to grow?
HK: Competitive price
As competition increases, attaining low costs is critical for biosimilar manufacturers to support discount and defend against competition. The biosimilar industry needs to keep reducing production costs to set a competitive price. With this in mind, Celltrion is working on a titer improvement and high value vial to maximise the price merit.
Despite biosimilars’ relatively long history, many European patients still lack awareness of biosimilars. Patients are primarily concerned about differences between the biosimilar and its reference product in terms of the molecular structure of the drug, and the potential for any differences in efficacy or safety.
As the patient awareness is hindrance to patients’ adherence, more education needs to be provided. Sharing the positive experiences of both healthcare professionals and patients and, in particular, highlighting best practice of biosimilars is very important. Biosimilar manufactures should work hard to actively change the awareness through biosimilar education, building partnerships and engaging with key stakeholders.
The industry should plan to not only make biosimilars but also add value to medicines by developing bio-betters and new medicines that offer enhanced convenience. Essentially, biologics are moving toward personalised medicines. The introduction of anti-drug antibodies and pharmacokinetics monitoring kits and subcutaneous formulations, all of which are going to be added to Celltrion’s infliximab biosimilar, is for the sake of improving the convenience and optimisation of the treatment.
BPR: What stage of development is the subcutaneous version of CT-P13 currently at and what is the advantage of this form of delivery?
HK: While the treatment of intravenous CT-P13, an infliximab biosimilar, is effective and well-tolerated, Celltrion anticipates that a new subcutaneous formulation would provide added patient convenience. CT-P13 SC is expected to be approved this year.
The subcutaneous formulation could offer a number of potential advantages to patients and healthcare providers, such as increased capacity for administration units by reducing chair time, and a lesser burden on patients as they do not need to visit a hospital to receive this treatment.
Since May 2016, Celltrion has conducted Phase I and Phase III clinical trials on the safety, pharmacokinetic and efficacy assessment of CT-P13 SC.
Celltrion has completed Phase III clinical trial for CT-P13 SC, with the preparation for filling a market authorisation application in Europe now in the final stage. Celltrion is set to complete the clinical analysis soon and to submit its application for Remsima SC to the European Medicines Agency in the second half of this year.
BPR: Celltrion previously suggested it had plans to add an additional third biosimilar manufacturing site outside of Korea – how is this developing?
HK: Celltrion is planning to construct a third factory in South Korea capable of producing 120,000 liters of drugs.