Biosimilars

Testing for unwanted immunogenicity from biologicals

Immunogenicity caused by biologicals, both originator and biosimilar, is an important issue that was raised by Dr Wadhwa from the National Institute for Biological Standards and Control [1].

Asian companies venture into biosimilars for kidney failure

Malaysia-based Chemical Company of Malaysia Berhad (CCM) wholly-owned subsidiary CCM Duopharma Biotech Berhad and Korea-based biotechnology company PanGen Biotech announced on 19 June 2012 that the companies had entered into an agreement to carry out a clinical trial of biosimilar erythropoietin in Malaysia to treat end stage renal failure patients.

iBio and GE Healthcare form new global alliance

Biotechnology company iBio, self-professed leader in the plant-made pharmaceutical field, and GE Healthcare, the health business of General Electric, announced on 26 July 2012 a new global alliance to commercialise plant-based technologies for the manufacture of biologicals and vaccines.

FDA urged to exclude plasma protein therapies from biosimilar pathway

FDA is being lobbied by patient and industry groups to exclude plasma protein therapies from its pathway for the approval of biosimilars. FDA has a mandate to create a new abbreviated process for the approval of biosimilars under the Biologics Price Competition and Innovation Act of 2009, which was part of the new healthcare reform law passed in March 2010 [1]. This potentially brings cheaper products to market sooner, and so increases the availability of affordable health care. However, it also means that manufacturers applying for approval for new biosimilars may be able to skip clinical testing if they can demonstrate sufficient similarity with reference products.

Deal struck over development of Herceptin biosimilar

Netherlands-based biopharmaceutical company Synthon announced on 18 July 2012 that it has entered into a global licensing agreement with Amgen and Watson Pharmaceuticals for the clinical development and testing of biosimilar trastuzumab as an alternative to Roche’s blockbuster anticancer agent Herceptin. The deal follows the results of a phase I trial reported on 22 March 2012 showing bioequivalence between Synthon’s trastuzumab and Herceptin [1].

Positive results from phase I study with biosimilar insulin glargine

Leading biotech company Biocon announced on 25 July 2012 positive results from a phase I comparative study conducted in Germany of its biosimilar insulin glargine in type 1 diabetes mellitus (T1DM) patients.

Biosimilar monoclonal antibody approved in Korea

South Korean biotechnology company Celltrion announced on 23 July 2012 that the Korean Food and Drug Administration (KFDA) had approved its first monoclonal antibody, Remsima.

US supreme court ruling means biosimilars pathway safe

On 28 June 2012 the US Supreme Court ruled in favour of the bulk of the Affordable Care Act, meaning that the biosimilars pathway, which is part of the act, is now also safe.

Biosimilar infliximab equivalence proven in phase III trial

Results from a phase III trial of biosimilar infliximab have proven the equivalence of South Korean biotechnology company Celltrion’s biosimilar (CT-P13) and the reference product – Johnson & Johnson’s rheumatoid arthritis blockbuster Remicade (infliximab) in terms of safety and efficacy in patients with active rheumatoid arthritis [1].

Copaxone sees off generics challenge

Teva received a major boost in June 2012, after a US court backed the Israeli firm in a patent dispute concerning its multiple sclerosis blockbuster Copaxone (glatiramer acetate).

US$67 billion worth of biosimilar patents expiring before 2020

Last updated: 20 January 2014

Twelve biological products with global sales of more than US$67 billion will be exposed to biosimilar competition by 2020, with Enbrel (etanercept) whose US patent has been extended until 2028, scoring global sales of US$7.3 billion by December 2011; coming in second after Humira (adalimumab) with global sales of US$7.9 billion [1].

Phase I trial of biosimilar infliximab proves biosimilarity

Results from a phase I trial of biosimilar infliximab have proven the equivalence of South Korean biotechnology company Celltrion’s biosimilar (CT-P13) and the reference product – Johnson & Johnson’s rheumatoid arthritis blockbuster Remicade (infliximab) in terms of pharmacokinetic parameters, as well as in safety and efficacy in patients with active ankylosing spondylitis [1].

Small molecule versus biological drugs

Biological drugs are large and complex, often consisting of heterogeneous mixtures. They are generally made in genetically engineered cells that impose their own variabilities–in post-translation modifications such as glycosylation–on the processes used to make such drugs.

Amgen welcomes biosimilar monoclonal antibody guideline

In a statement issued on 18 June 2012, biologicals major Amgen announced that the company broadly supports the scientific principles behind the guideline on non-clinical and clinical aspects for biosimilar monoclonal antibodies recently issued by EMA [1]. The company added that the guideline aims at maintaining a high standard for approval of a biosimilar in the EU.

Trials of biosimilar monoclonal antibody prove biosimilarity

South Korean biotechnology company Celltrion presented the PLANET clinical studies results of phase I and phase III trials for its first monoclonal antibody biosimilar (CT-P13) of Johnson & Johnson’s rheumatoid arthritis blockbuster Remicade (infliximab) at the Annual Congress of the European League Against Rheumatism (EULAR) held in Berlin, Germany, on 6–9 June 2012. The results demonstrated the biosimilarity of CT-P13 to the reference drug, supporting the company’s intention to launch the biosimilar monoclonal antibody globally.

Successful phase III trial of biosimilar r-FSH

Finox Biotech announced on 6 June 2012 that the company’s pivotal phase III study with Afolia, a biosimilar recombinant follicle stimulating hormone (r-FSH), in patients undergoing assisted reproduction technology (ART), had met its primary endpoint.

Merck KGaA and Dr Reddy’s to collaborate on biosimilar mAbs

Pharma major Merck KGaA announced on 6 June 2012 its first steps into the biosimilars market, with an agreement with India-based generics manufacturer Dr Reddy’s Laboratories (Dr Reddy’s) to co-develop biosimilar cancer drugs.

Prescriber caution is likely over biosimilars

The experience with generic medicines is a sign that prescribers are likely to be cautious, and in some cases concerned, about the use of biosimilars as alternatives to brand-name drugs.

Alternative delivery devices for biosimilars

FDA, in its draft guidance for biosimilars, has said that biosimilars can use different drug delivery devices than the corresponding reference product.

Biosimilars approved and marketed in The Netherlands

Last updated: 1 June 2012

The Dutch Medicines Evaluation Board (MEB) – College ter Beoordeling van Geneesmiddelen (CBG) – is responsible for the approval of marketing authorisation of medicinal products including biosimilars in The Netherlands.

FDA’s public hearing on biosimilars draft guidances

On 11 May 2012, FDA held a public hearing to gain input on their draft guidances relating to the development of biosimilar products and it seems that the guidances were generally well accepted.

Immunogenicity of biologicals

This article discusses the issue of immunogenicity with respect to originator biologicals and biosimilars [1].

US Supreme Court looks set to challenge Affordable Care Act

The United States Supreme Court is reviewing the constitutionality of the provision in the Affordable Care Act providing that individuals should take personal responsibility for paying for their health care by obtaining health insurance or pay a fine. The move could mean that the Supreme Court rejects the whole healthcare law, including the biosimilars pathway created by the healthcare reform.

Biosimilars approved and marketed in Belgium

Last updated: 18 May 2012 

The Federal Agency for Medicines and Health Products (FAMHP), formerly the Directorate-General for Medicinal Products of the Federal Public Service (FPS) Public Health, created in January 2007, is the official authority for medicines and health products in Belgium and is also responsible for authorising biosimilars in Belgium [1]. This is carried out via the EU procedures (centralised, national, mutual recognition or decentralised) and following EMA guidelines for biosimilars.

Daiichi Sankyo and Coherus BioSciences make biosimilars deal

Coherus BioSciences and Daiichi Sankyo announced on 7 May 2012 that the two companies had made an exclusive agreement to develop and commercialise biosimilars of etanercept and rituximab in certain Asian countries including Japan.

Biosimilar filgrastim provides cost savings for treating febrile neutropenia

Professor Aapro and co-authors have performed a cost-efficiency analysis for the three most common granulocyte colony-stimulating factors (G-CSF) products used to treat febrile neutropenia: filgrastim (Neupogen, Amgen) and its biosimilar (Zarzio, Sandoz/Novartis) and the pegylated form of filgrastim, pegfilgrastim (Neulasta, Amgen) [1]. Filgrastim is more cost-efficient than pegfilgrastim for up to 12 days of treatment: beyond 12 days, pegfilgrastim becomes the most cost-efficient of the two. But above all, biosimilar filgrastim is the most cost saving compared to both originator filgrastim and pegfilgrastim.

Also noted on biosimilars: 11 May 2012

Sandoz testimony at FDA hearing on biosimilars will emphasise need for consistent regulatory standards across all biologicals
Sandoz announced on 9 May 2012 that Dr Mark McCamish, Head of Global Biopharmaceutical Development, would present on behalf of the Novartis Group of companies (Novartis) at the 11 May 2012 FDA public hearing on draft guidances for biosimilars.

The message he will convey will focus on the need for a single science-based regulatory standard that FDA should apply across all biologicals, irrespective of the business model of the sponsor. As well as a single standard, Dr McCamish will address the points that biosimilar clinical studies should be only confirmatory and the fact that interchangeability is critical to maximising access to affordable biosimilars for US patients.

Source: Sandoz

Bayer opposes sorafenib compulsory licence in India

German pharma giant Bayer told Reuters on 5 May 2012 it had challenged a decision by the Indian Government, which allows India-based generics firm Natco Pharma to sell a generic version of Bayer’s liver and kidney cancer drug Nexavar (sorafenib) in India, before its patent expires in 2020.

Abbott asks FDA to block adalimumab biosimilar

Abbott Laboratories (Abbott) submitted a 30-page citizen petition to FDA on 2 April 2012 asking the agency to reject any biosimilar for its rheumatoid arthritis drug Humira (adalimumab). Abbott says that FDA would be forced to use trade secrets included in Humira’s Biologics License Application (BLA) to approve biosimilars. Abbott is therefore requesting that FDA refuses to review any biosimilar biological whose BLA was submitted before the Biologic Price Competition and Innovation (BPCI) Act of 2009 came into effect on 23 March 2010.

Bioavailability comparison of brand-name and generic acetylcysteine in China

A study comparing brand-name and generic acetylcysteine in China by Liu et al has shown that the generics test formulation was bioequivalent to the originator drug [1].

EMA reviews its first biosimilar monoclonal antibody

According to EMA’s list of applications for new human medicines under evaluation by the Committee for Medicinal Products for Human Use released in April 2012 the agency will be reviewing a new application for a biosimilar version of infliximab.

Study of biosimilar enoxaparins in Brazil

Analysis of biosimilar enoxaparins available for clinical use in Brazil by the Laboratório de Tecido Conjuntivo in Brazil have shown that the biosimilar preparations of enoxaprain are similar to the originator drug [1].

Novartis versus the Indian patent system

The Indian patent system is once again under scrutiny as a final decision in the case of Novartis versus the Indian patent system is eagerly awaited by originator biologicals and biosimilars manufacturers alike. However, any decision on the case has been delayed until 10 July 2012.

Samsung to launch biosimilars by 2015 at half the current prices

South Korean electronics giant Samsung told the Financial Times that it plans to launch biosimilars by 2015 at half the prices that patients in Europe and the US currently pay.

Biocon opens new research centre

Indian biosimilars major Biocon, announced on 5 April 2012 the opening of a new state-of-the-art Integrated Research and Development Centre in Bangalore, India.

EMA publishes procedural advice for biosimilars

On 11 April 2012, EMA published a new document on regulatory procedural advice for biosimilars.

Biosimilars dilemma over reference products

Global manufacturers of biosimilars have a dilemma on their hands concerning reference products. What to do to reduce the burden of data required in different countries and regions of the world to get their biosimilars onto the market?

Also noted on biosimilars: 13 April 2012

Palivizumab biosimilar successfully produced in plants
Biotechnology company iBio, self-professed leader in the plant-made pharmaceutical field, announced on 10 April 2012 that it had successfully used its iBioLaunch technology to produce biosimilar palivizumab in non-transgenic green plants.

This is the second monoclonal antibody that the company has successfully produced. Back in October 2011 the company announced the successful use of its technology to produce rituximab.

Related article

Rituximab biosimilar successfully produced in plants

Source: iBio

Current and future issues surrounding biosimilars

Biological medicines are already becoming an increasingly important part of health care. With patent expiries on originator biological products, biosimilars are also increasingly become a part of this future [1]. In fact, by 2020 twelve of the top-selling biologicals will have lost patent protection, opening up an estimated US$24 billion in EU sales and US$30 billion in US sales [2].

BIO and GPhA support biosimilar and generic user fees

Both the Biotechnology Industry Organization (BIO) and the Generic Pharmaceutical Association (GPhA) have expressed their support of user fees for biosimilars and generics.