Biosimilars

Hospira's biosimilar filgrastim recommended for EU approval

On 18 March 2010, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorisation for Hospira’s biosimilar product Nivestim (filgrastim), 12 MU/0.2 mL, 30 MU/0.5 mL, 48 MU/0.5 mL solution for injection or infusion intended for the treatment of neutropenia.

South Korea to emerge as global leader in biosimilar R & D

According to the South Korea Pharmaceuticals and Healthcare Report Q2 2010 released by Business Monitor International (BMI) in March 2010, South Korea will emerge as a global leader in biosimilar research and development.

AutekBio to build ‘Asia’s largest biologics contract manufacturing organisation’ in China

AutekBio, Inc. –with headquarters in the Bay Area of California, USA, but operations in China– will build one of Asia’s largest biologic contract manufacturing organisation (CMO) facilities in southern Beijing, China. To construct the facility, AutekBio signed a deal securing US$100 million in venture capital from private and government sources. Contributing to the capital raise were SUMA Ventures and Beijing E-Town Harvest International Capital Management Corporation, Beijing’s Municipal Government’s venture capital group. The new joint venture will build a world class R & D and manufacturing centre in southern Beijing, to service international biologic developments, with combined volumes of bioreactors up to 20,000 L in multiple production lines (trains).

For complex biosimilars in EU: drop clinical comparability

Clinical trials required by European regulators to compare biosimilar products with corresponding biologic brands are surplus to requirements and may even be a barrier for the development of biosimilars of more complicated biologics, state Professor Huub Schellekens and Dr Ellen Moors of Utrecht University, The Netherlands, in a Nature Biotechnology Commentary of January 2010. “If you look in detail at the accepted and rejected biosimilars and the differences, then you might conclude that proof of clinical equivalence is actually overdue,” comments Professor Arnold Vulto of the Erasmus MC, Rotterdam.

New method for producing human-like glycosylated MAbs

As reported online on 28 February 2010 in Nature Chemical Biology, Professor Lai-Xi Wang, Professor Markus Aebi and colleagues describe a new bacterial method for producing homogeneous eukaryotic N-glycoproteins.

GTC achieves high-level production of TG20, a biobetter anti-CD20 MAb with enhanced antibody-dependent cell-mediated cytotoxicity

GTC Biotherapeutics announced on 1 March 2010 that it has achieved high-level production of TG20; an anti-CD20 monoclonal antibody (MAb). The TG20 MAb, which is produced in the milk of transgenic goats, is being co-developed by GTC and LFB as part of an LFB-GTC joint venture.

Glycosylation technologies for biosimilars and ‘biobetters’

According to Mr Hans Baumeister and Mr Steffen Goletz of Glycotope, human cell lines providing a human glycosylation pattern – such as those of Crucell (PER.C6), Cevec (CAP) and Glycotope (GlycoExpress) – have attracted increasing amounts of attention over the past years. In the case of biosimilars, regulatory approval now requires an extensive programme of bioequivalence studies to be undertaken to characterise the product in terms of its biochemical properties, safety and activity. As a consequence, glycosylated biosimilars need to be equipped with a similar pattern of glycosylation. For example, the degree of sialylation should not deviate by more than 20% from that of the original product. Hence, the chosen cell clone with high productivity has to be able to provide post-translational modifications as closely related to the originator’s cell line as possible. However, since glycosylation differs within clones, during the bioequivalence study it is often realised that the product carries different carbohydrates, usually resulting in a hyposialylation; this requires the screening process to be repeated in order to identify a new cell clone that is able to provide the equivalent glycosylation. Several glycosylation analysis technologies are available for the development and production of glycosylated biotherapeutics, applicable to both biosimilars and second-generation ‘biobetters’ (see Table 1).

Biosimilar epoetin zeta gets positive EMA-CHMP opinion for SC route in renal patients in EU

Hospira announced on 22 February 2010 that the EMA’s Committee for Medicinal Products for Human Use (CHMP) has recommended for approval the administration of Retacrit (epoetin zeta) subcutaneously in the nephrology setting. This provides an alternative option to intravenous (IV) delivery of the drug for the symptomatic treatment of anaemia associated with chronic renal failure. Final approval by the European Commission is expected in the next few months, which will result in marketing authorisation for Retacrit subcutaneous (SC) administration in all EU Member States.

Rituximab gets US FDA approval for chronic lymphocytic leukaemia

The US FDA has approved Roche’s Genentech/Biogen Idec's anti-CD20 monoclonal antibody Rituxan/MabThera (rituximab) plus chemotherapy for people with either previously untreated or previously treated (relapsed or refractory) chronic lymphocytic leukaemia (CLL).

As pointed out by Scrip, MabThera was approved in the EU in 2009 for these same indications. However, US approval was held up by a complete response letter issued by the FDA in November 2009. The companies said then that the agency had not requested any new data to complete its review of these applications, but that they were continuing final labelling discussions.

How to tackle overcapacity in monoclonal antibody production

In the early days, most monoclonal antibody (MAb) therapies required high dosages, as pointed out by Ms Gail Dutton in a Genetic Engineering & Biotechnology News Feature Article on 15 February 2010 (see also Monoclonal antibodies modelling - predictive analytics, Improving monoclonal antibody production - antibody-drug conjugate technology and Modern monoclonal antibody production - focus on quality by design, timelines, cost)

Monoclonal antibodies modelling - predictive analytics

Improved analytics is helping to ensure that the active pharmaceutical ingredient (API) quality attributes of monoclonal antibodies (MAbs) are identified as early as possible, determining both the desirable and undesirable characteristics, as pointed out by Ms Gail Dutton in a Genetic Engineering & Biotechnology News Feature Article on 15 February 2010 (see also How to tackle overcapacity in monoclonal antibody production, Improving monoclonal antibody production - antibody-drug conjugate technology and Modern monoclonal antibody production - focus on quality by design, timelines, cost)

Improving monoclonal antibody production - antibody-drug conjugate technology

Researchers are developing new approaches to improve monoclonal antibody (MAb) production, as pointed out by Ms Gail Dutton in a Genetic Engineering & Biotechnology News Feature Article on 15 February 2010 (see also How to tackle overcapacity in monoclonal antibody production, Monoclonal antibodies modelling - predictive analytics and Modern monoclonal antibody production - focus on quality by design, timelines, cost)

Modern monoclonal antibody production - focus on quality by design, timelines, cost

In the decade since severe capacity constraints limited monoclonal antibody (MAb) production, the industry has adjusted, so that today, overcapacity is the issue, along with developing techniques to ensure product quality, reduce development timelines, and decrease costs, writes Ms Gail Dutton in a Genetic Engineering & Biotechnology News Feature Article on 15 February 2010. Many of these issues will be explored at IBC’s conference on ‘Antibody Development and Production’ in March 2010 as she points out.

Will the EU biosimilars pathway be applicable to monoclonal antibodies?

To what extent is the existing framework for biosimilars in Europe likely to be applicable to monoclonal antibodies (mAbs)? This question was verified in a paper by Dr Christian Schneider –member of the EMA’s Committee for Medicinal products for Human Use (CHMP), Chairman of EMA’s Biological Medicines Working Party (BMWP) and the Paul-Ehrlich-Institut in Langen, Germany– and Dr Ulrich Kalinke of the Paul-Ehrlich-Institut and Twincore Center for Experimental and Clinical Infection Research in Hannover, Germany, as published in Nature Biotechnology of September 2008.

A follow-on biologic drug is not a ‘biogeneric’: Lessons from Omnitrope and Valtropin

In an article by Dr Robert Roth and Dr Nicholas Fleischer of the Weinberg Group published in Journal of Generic Medicines of May 2009, it is stated that a follow-on biologic drug is not a ‘biogeneric’, based on lessons from Sandoz’s biosimilar human growth hormone Omnitrope (somatropin) and BioPartners’ Valtropin (somatropin).

PhRMA, Amgen correct NEJM article on biologics exclusivity

In a NEJM Letter to the Editor of 18 February 2010, Mr David Wheadon, Senior Vice President of the Scientific & Regulatory Affairs team of the Pharmaceutical Research and Manufacturers of America 
(PhRMA) –having been employed by several pharmaceutical companies (Eli Lilly, GlaxoSmithKline, Abbott) and holding stock in Abbott Laboratories and GlaxoSmithKline– corrects the NEJM Perspective article by Mr Engelberg et al. of 12 November 2009, writing that “the record should be set straight” with regard to the market exclusivity of biologicals in the biosimilars debate.

FDA approves Amgen’s and Johnson & Johnson's the risk evaluation and mitigation strategy (REMS) for erythropoiesis-stimulating agents (ESAs)

Amgen and Johnson & Johnson (J&J) announced on 16 February 2010 that the US FDA approved the companies' risk management strategy for patients with chemotherapy-induced anaemia who are receiving erythropoiesis-stimulating agents (ESAs), including Amgen's Aranesp (darbepoetin alfa) and Epogen (epoetin alfa), and Johnson & Johnson's Procrit (epoetin alfa).

Improving effector functions of MAbs for cancer treatment: Enhancing antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC)

Mr Akito Natsume et al. of Kyowa Hakko Kirin, Machida-shi, Tokyo, Japan, have shown to improve effector functions of monoclonal antibodies (MAbs) for cancer treatment by enhancing ADCC and CDC, as published in their review article in Drug Design, Development and Therapy 2009:3 of December 2008.

Aglycosylated IgG mAbs can be engineered to display unique FcγR selectivity that mediate antibody dependent cell-mediated cytotoxicity

Until recently, bacterially derived monoclonal antibodies (mAbs) were unable to recruit innate immune cells and were thus ineffective at raising an attack against tumour cells. However, Mr George Georgiou et al. of the University of Texas, Austin, found that engineered mutations in the Fc domain can improve innate immune cell recognition by mAbs manufactured in bacteria, as published in the Proceedings of the National Academy of Sciences.

The study stems from efforts to make therapeutically useful mAbs in bacteria. A key roadblock is that bacterially manufactured antibodies lack Fc region glycosylation. “Antibodies that are not glycosylated cannot be recognised by immune cells,” said Mr Georgiou. In the article it is described how aglycosylated IgG variants expressed in bacteria that selectively bind FcγRI potentiate tumour cell killing by monocyte-dendritic cells. The authors explain that the N-linked glycan of immunoglobulin G (IgG) is indispensable for the interaction of the Fc domain with Fcγ receptors on effector cells and the clearance of target cells via antibody dependent cell-mediated cytotoxicity (ADCC). E.coli-expressed, aglycosylated Fc domains bind effector FcγRs poorly and cannot elicit ADCC.

US FDA prepares for biosimilars in 2011 budget plan, despite stalled healthcare reform bill

Increasing inspections and creating a regulatory pathway for the approval of biosimilars are among the most important areas of the US FDA's fiscal 2011 budget request, US Department of Health and Human Services (HHS) Secretary Ms Kathleen Sebelius says. In testimony before the House Energy and Commerce Committee on 4 February 2010, Ms Sebelius focused on funds included in the budget request for the FDA's efforts to improve medical product safety, including increased inspections and investment in tools to enhance the safety of increasingly complex drugs and biologics.

Bionomics of biosimilars - Indian options for investors

As reported by Ms Nayantara Som in BioSpectrumIndia of 13 January 2010, biosimilars are said to be the next big cash cow for India. However, players have many knots to untangle before they can have a firm grip over the economics of the market.

Bionomics of biosimilars – EU and US markets not easy for India

As reported by Ms Nayantara Som in BioSpectrumIndia of 13 January 2010, biosimilars are said to be the next big cash cow for India. However, players have many knots to untangle before they can have a firm grip over the economics of the market, she warns.

Bionomics of biosimilars – Indian opportunities

As reported by Ms Nayantara Som in BioSpectrumIndia of 13 January 2010, biosimilars are said to be the next big cash cow for India. However, players have many knots to untangle before they can have a firm grip over the economics of the market.

Bionomics of biosimilars – India’s next big cash cow?

As reported by Ms Nayantara Som in BioSpectrumIndia of 13 January 2010, biosimilars are said to be the next big cash cow for India. According to her, however, players have many knots to untangle before they can have a firm grip over the economics of the market.

FDA accepts Teva’s biosimilar filgrastim BLA, Amgen not

The US FDA has accepted Teva‘s application to sell a biosimilar version of Amgen's Neupogen (filgrastim), although the biotech giant is working to block the move in court.

XM02, a granulocyte colony-stimulating factor (G-CSF), is designed to treat severe neutropenia, a haematological disorder characterised by an abnormally low number of white blood cells. If approved, the drug would be marketed under the name Neutroval by US pharma company Hospira, which in 2009 acquired worldwide rights to the new version in a deal that also saw it gain manufacturing capacity for filgrastim and pegfilgrastim - a long-acting version of the drug marketed by Amgen as Neulasta. The worldwide market for Neulasta and Neupogen currently stands at more than US$2 billion.

Abbott: Non-responding RA patients with anti-infliximab antibodies may switch to less immunogenic anti-TNF

In the race for biosimilar/biobetter monoclonal antibodies (MAbs), it is interesting to compare originator MAbs, e.g. mouse-human chimeric infliximab (Remicade) of Johnson & Johnson’s Centocor versus Abbott’s fully human – and thus less immunogenic – adalimumab (HUMIRA).

Celtic Pharma invests in Cantab, PolyTherics for ‘biosuperiors’

As reported by Genetic Engineering & Biotechnology News on 25 and 26 January 2010, Celtic Pharma Holdings is making an initial £5 million (about $8.1 million) investment in Cantab Biopharmaceuticals, Cambridge, UK. Cantab is wholly owned by the Celtic Pharma Holdings II LP (CP2) fund. The new CP2 funding will be spread over three years and will support the development of the firm’s first clinical-stage so-called ‘biosuperior’ biologic in haematology.

Korean biopharma: special programme for biosimilars

As reported by Narayan Kulkami, Singapore, in BioSpectrum Asia Edition on 18 January 2010, the Korean biopharmaceutical sector gets support for biosimilars and/or biobetters.(see also Korean biopharma gets support for biosimilars/biobetters)

Korean biopharma gets support for biosimilars/biobetters

As reported by Narayan Kulkami, Singapore, in BioSpectrum Asia Edition on 18 January 2010, the [South] Korean biopharmaceutical industry continues to get the attention of the global players, mainly because the Korean government in 2009 identified ‘biopharmaceutical and medical equipment’ as one of the future engines for economic growth. The life sciences industry in Korea consists of close to 2000 companies including 580 pharmaceutical companies and 600 biotech companies. (see also Korean biopharma: special programme for biosimilars)

ADCC enhancement technologies for monoclonal antibodies

In a 2009 article by Dr Cheng Liu, founder and CEO of Eureka Therapeutics in California, and Andreia Lee in Trends in Bio/Pharmaceutical Industry on Antibody Therapeutics, it is stated that ADCC (Antibody Dependent Cell-mediated Cytotoxicity) enhancement is a key strategy for improving therapeutic antibody drug efficacy against cell-surface targets in cancer and chronic inflammation. It takes advantage of patients’ innate immune cells to kill target cells. The functions are primarily triggered through direct interaction of the Fc domain of human immunoglobulin (in most cases IgG1) with the corresponding receptors. Therapeutic antibodies with enhanced ADCC are anticipated to have a clinical advantage owing to increased specific lysis of target cells, such as cancer cells, mediated by Fc receptors present on natural killer cells, macrophages, and other immune cell types.

Biosimilar EPO and infliximab, adalimumab get formal Japanese approval

As reported by Scrip on 21 January 2010, a large batch of new products has received final approval from Japan's ministry of health, labour and welfare, including a biosimilar erythropoietin. These and the other products given formal approval by the ministry received positive recommendations in November and December 2009.

Xencor: Via Fc engineering enhanced antibody half-life improves in vivo activity

Improved affinity for the neonatal Fc receptor (FcRn) is known to extend antibody half-life in vivo. However, this has never been linked with enhanced therapeutic efficacy. Mr Jonathan Zalevsky and Dr John Desjarlais et al. of Xencor at Monrovia, CA, USA, studied if such enhanced antibody half-life improves in vivo activity, as published online in Nature Biotechnology on 17 January 2010.

Medarex: With CDA1, CDB1 MAbs better metronidazole or vancomycin treatment against C difficile toxins

New therapies are needed to manage the increasing incidence, severity, and high rate of recurrence of Clostridium difficile infection in which toxins A and B cause pseudomembranous colitis. This is associated with bleeding and a severe form of diarrhoea, which together can lead to perforation of the lower bowel and even death.

Ustekinumab better than etanercept in psoriasis trial

In a study by Christopher Griffiths et al. of the University of Manchester, UK, Johnson & Johnson (J&J)’s monoclonal antibody STELARA (ustekinumab, an interleukin-12 and interleukin-23 blocker) and Amgen’s Enbrel (etanercept, an inhibitor of tumour necrosis factor: anti-TNF) have been compared for the treatment of psoriasis, as published in The New England Journal of Medicine (NEJM) of 14 January 2010. The Phase 3, Multicenter, Randomized Study Comparing CNTO 1275 and Etanercept for the Treatment of Moderate to Severe Plaque Psoriasis’ was sponsored by J&J’s Centocor.

Innovation over imitation: New FOBs technologies, players

In an article by Xencor President and CEO Bassil Dahiyat, published in Pharmaceutical Executive on 4 November 2009, tables are presented on new technologies for creating ‘biobetter’ follow-on biologics (FOBs) and potential ‘Big Pharma’ players in FOBs.

Innovation over imitation - How to deliver FOBs on the bottom line

In an article by Xencor President and CEO Bassil Dahiyat, published in Pharmaceutical Executive on 4 November 2009, the development of ‘biobetter’ follow-on biologics (FOBs) — optimised versions of pioneer drugs that have improved pharmaceutical properties but carry only minor changes in structure — is discussed.

Innovation over imitation - Charting the FOBs landscape

In an article by Xencor President and CEO Bassil Dahiyat, published in Pharmaceutical Executive on 4 November 2009, the development of ‘biobetter’ follow-on biologics (FOBs) — optimised versions of pioneer drugs that have improved pharmaceutical properties but carry only minor changes in structure — is discussed.

Innovation over imitation: Tools to compete and win with ‘biobetter’ FOBs

In an article by Xencor President and CEO Bassil Dahiyat, published in Pharmaceutical Executive on 4 November 2009, the development of ‘biobetter’ follow-on biologics (FOBs) — optimised versions of pioneer drugs that have improved pharmaceutical properties but carry only minor changes in structure — is discussed.

Innovation over imitation: High-cost biosimilar FOB development, slow uptake

In an article by Xencor President and CEO Bassil Dahiyat, published in Pharmaceutical Executive on 4 November 2009, the development of ‘biobetter’ follow-on biologics (FOBs) — optimised versions of pioneer drugs that have improved pharmaceutical properties but carry only minor changes in structure — is discussed.

Innovation over imitation: ‘Biobetter’ follow-on biologics

In an article by Xencor President and CEO Bassil Dahiyat, published in Pharmaceutical Executive on 4 November 2009, the development of ‘biobetter’ follow-on biologics (FOBs) — optimised versions of pioneer drugs that have improved pharmaceutical properties but carry only minor changes in structure — is discussed.