E-DRUG: The Utrecht Centre of Excellence for Affordable Biotherapeutics for
Public Health
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[all the texts below are sourced from
http://www.uu.nl/en/organisation/utrecht-centre-of-excellence-for-affordable-biotherapeutics/
Copied as fair use. WJB]
The WHO and University Utrecht (Netherlands) today announced the set up of a
new WHO collaborating centre:
The Utrecht Centre of Excellence for Affordable Biotherapeutics for Public
Health (UCAB) is the result of a collaboration between Utrecht University and
the World Health Organisation. UCAB is a non-profit foundation that aims to
facilitate the development and distribution of high quality and affordable
biotherapeutics in low and middle income countries.
UCAB
Mission: Our mission is to improve global health by helping to make high
quality and affordable biotherapeutics accessible to patients throughout the
world in a sustainable fashion.
Why a centre of Excellence? Unmet medical needs in Low and Middle Income
Countries
Since the market authorisation of the first recombinant insulin in 1982 and the
first monoclonal antibody in 1992, biological therapeutics (biologicals) have
been developed to treat a variety of diseases, including cancer and autoimmune
diseases. Although the use of biopharmaceuticals has expanded in high income
countries, low and middle income countries (LIMCs) have been largely devoid of
these products, notwithstanding a considerable medical need1. As the first
biopharmaceuticals products have lost, or are about to lose their patent
protection, opportunities have arisen to develop affordable copy versions
(biosimilars) of these products. However, currently available biosimilars are
still too expensive for most patients in LMICs.
In various countries cheaper copies of biological products have been available
for many years, mainly predating the existence of biosimilar regulatory
guidelines. These products mostly did not complete the rigorous comparability
exercise that is advocated in the current WHO guidelines and some may be of
questionable quality. It is thus of the utmost importance that the products
that are available in LMICs adhere to international quality standards.
1. Lopes Gde, L.,Jr, de Souza, J. A. & Barrios, C. Access to cancer medications
in low- and middle-income countries. Nat. Rev. Clin. Oncol. 10, 314-322 (2013).
The first project will be to produce the monoclonal antibody palivizumab, used
in the prevention of RSV respiratory infections.
RSV
Respiratory syncytial virus (RSV) is the leading cause of hospitalisations in
infants and young children and the leading cause of acute lower respiratory
infections (ALRI) in children globally. The annual global incidence of RSV
infection has been estimated at 64 million and is estimated to cause
approximately 33.8 million new episodes of ALRI in children annually, of which
96% occur in developing countries. In addition, RSV is the most common viral
cause of death in children younger than 5 years of age and has been estimated
to cause up to 199,000 deaths per year. As a comparison, global measles deaths
are estimated at 164,000. Infections are more severe in premature infants and
in those with subjacent illness (such as chronic lung disease, congenital heart
disease and HIV).1 Globally, about 15 million neonates are born prematurely
(defined as before 37 weeks of gestation) each year, which corresponds to more
than one in 10 of all neonates.2 So far, no safe and efficacious vaccine
against RSV has been approved. Although some vaccines are under development, it
remains uncertain if these will prove to and be effective in protecting preterm
or immunocompromised infants.
Palivizumab
Currently there is only one medical intervention available against RSV: Monthly
intramuscular injections of the monoclonal antibody palivizumab (Synagis®) to
high-risk infants to serve as a prophylaxis for reducing the incidence of
hospitalisation. In countries with a clear seasonal pattern the treatment is
generally recommended during the winter months or rainy season and is
authorised to be administered to neonates born less than 35 weeks gestation.
However, the cost of treatment with palivizumab has been estimated at around €
4000 per season (five doses)3, with some estimates as high as US$ 9,615 per
season. Set at this price, palivizumab is out of reach for many patients in
LMICs. The patent on the technology will expire in 2015, opening up
opportunities for biosimilar versions on the market. However, so far there has
been little interest from biosimilar manufacturers in developing this product.
1. Tempia, S. et al. Mortality associated with seasonal and pandemic influenza
and respiratory syncytial virus among children <5 years of age in a high HIV
prevalence setting--South Africa, 1998-2009. Clin. Infect. Dis. 58, 1241-1249
(2014).
2. Prescott, W. A.,Jr, Doloresco, F., Brown, J. & Paladino, J. A. Cost
effectiveness of respiratory syncytial virus prophylaxis: a critical and
systematic review. Pharmacoeconomics 28, 279-293 (2010).
3. Nuijten, M. J. & Wittenberg, W. Cost effectiveness of palivizumab in Spain:
an analysis using observational data. Eur. J. Health. Econ. 11, 105-115 (2010).
About Biosimilars
Biosimilars are copy versions of biological products whose patents have
expired. Unlike small molecules, biologicals are very large and intricate
molecules that are subject to extensive post-translational modifications that
are sensitive to differences in manufacturing conditions. Therefore, biological
products are complex mixtures that cannot be completely characterised using
existing analytical methods. Because of these limitations, biosimilar
regulatory pathways have been established throughout the world. These pathways
allow the authorisation of a biopharmaceutical through the demonstration of
‘biosimilarity’ to an already approved ‘reference product’ by completing an
extensive ‘comparability exercise’.
The extent of this comparability exercise differs globally, but an increasing
number of countries have adopted regulations modelled after the WHO guidelines
on evaluation of similar biotherapeutic products (SBPs). These guidelines
advise a stepwise approach, including the provision of a full quality dossier,
appropriate nonclinical studies, pharmacokinetic and pharmacodynamic studies,
and, finally, comparative clinical studies (either confirmatory PK/PD, or
therapeutic efficacy studies) to confirm a comparable benefit risk profile to
the chosen reference product.
Costs of biotherapeutics
Currently authorised, top selling monoclonal antibodies are sold at prices
ranging from €1000-€100.000 per year, whereas the estimated costs of goods for
producing monoclonal antibodies are estimated at around 2.3% of the sales
price.1 Clearly, there is great opportunity to reduce the costs of these
products once their patents expire.
However, developing biosimilars requires considerable technological expertise.
Compared to small molecule generics, the development process is long (5-10
years) and costly, with estimated investment costs ranging from US$ 40-200
Million for a biosimilar. Biosimilar products authorised in Europe are being
sold at prices that are only 30%-40% lower than the innovator.2 While this may
lead to considerable cost savings, such high costs still put these products out
of reach for most patients in LMICs. In order to improve access to
biotherapeutics in LMICs, the costs of these treatments require substantial
reductions.
1. Kelley, B. Industrialization of mAb production technology: the bioprocessing
industry at a crossroads. MAbs 1, 443-452 (2009).
2. IMS health. Shaping the biosimilars opportunity: A global perspective on the
evolving biosimilars landscape. Available from:
http://www.imshealth.com/ims/Global/Content/Home%20Page%20Content/IMS%20News/Biosimilars_Whitepaper.pdf
[Accessed 17 July 2012]. (2011).
The driving force behind the new Centre of Excellence is Huub Schellekens, its
Director.
Huub Schellekens is professor of Pharmaceutical Biotechnology at Utrecht
University in the Netherlands. He teaches Medical Biotechnology at the
Innovation Studies Group and has a research position at the Department of
Pharmaceutical Sciences at the same university.
E-drug welcomes more discussion on biosimilars
Wilbert
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Wilbert Bannenberg, E-drug moderator
wjb@wxs.nl
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