Regenerative medicine - Science and Technology Committee Contents


Chapter 3: The Current landscape

Impact and excellence of the science base

28.  The UK has a strong science base in regenerative medicine. The Department for Business, Innovation and Skills (BIS) commissioned Thomson Reuters to analyse the quality and impact of UK regenerative medicine research as part of its taking stock exercise. It found that, compared with continental averages, the UK had more highly cited research on average than the rest of Europe and Asia. North America outperformed the UK in the number of "very highly" cited articles but the UK has a strong, world-class, science base in this field.[54]

29.  The UK has multiple academic centres of excellence in the field including the Wellcome Trust—Medical Research Council (MRC) Cambridge Stem Cell Biology Institute and the University of Edinburgh MRC Centre for Regenerative Medicine, as well as centres in London, Oxford and Newcastle.[55] UK researchers are "significant and regular" contributors to international scientific conferences on regenerative medicine and stem cell research.[56] Professor Michael Linden, King's College London, summed up the UK's current strength as follows: "the per capita impact that UK scientists have compared with the rest of the world—I mean UK science and biomedical science in particular—is very high".[57]

30.  The Oxford Stem Cell Institute (OSCI) said that "the UK scores well in all metrics of academic output in the stem cell field, having particular strengths in disciplines such as induced pluripotency, bioengineering and scaffold design, transplantation immunology and medicinal chemistry. Many groups are of international standing and produce publications that are both influential and highly-cited".[58] Other areas of strength highlighted to us included haematopoietic stem cell research, developmental biology, gene therapy, tissue engineering and human embryonic stem cell biology.[59] Leukaemia and Lymphoma Research (LLR) offered a number of disease-specific examples: "academically the UK is leading the world in the development of cell and gene therapies for a wide range of inherited and acquired disorders including blindness, deafness, degenerative neurological conditions and cancer".[60]

Historical strengths

31.  Prominent UK academics include three Nobel Prize winners: Professor Sir Martin Evans FRS, who discovered the principles for introducing specific gene modifications in mice using embryonic stem cells;[61] the late Professor Sir Robert Edwards FRS, who developed human in vitro fertilization (IVF) therapy[62]; and Professor Sir John Gurdon FRS, who pioneered methods to "reprogram" cells to an embryonic state.[63] The UK is also responsible for some of the developmental biology which underpins the iPS (induced pluripotent stem cells) work in Japan and the US, for which Professor Shinya Yamanaka shared the 2012 Nobel Prize with Professor Sir John Gurdon.[64] Examples of ongoing work exploring the underpinning science of regenerative medicine in the UK include: understanding mechanisms of pluripotency, the interaction between stem cells and bioengineered surfaces, and advanced imaging techniques to monitor stem cell behaviour in living tissues.[65]

32.  We consider the translation of basic science to clinical research in greater depth in the next Chapter. There are a great many areas of basic science related to regenerative medicine which need further investigation, and clinical research will bring to light areas where further research is required, for example to explain underpinning mechanisms.

Clinical trials

33.  Clinical trials are medical research studies to test whether different treatments are safe and how well they work.[66] Figure 1 (overleaf) sets out the different stages of clinical trials:

FIGURE 1

Clinical trial stages[67]

34.  The UK had the second highest number of clinical trials involving ATMPs in Europe during the period 2004-10.[68] Table 3 gives details of the number of ATMP clinical trials broken down by EU Member State.

TABLE 3

ATMP clinical trials in Europe in the period 2004-10[69]
Country
Phase of Clinical Trial
Distribution of Clinical Trials
I
I/II
II
II/III
III
III/IV
IV
TOTAL
National
Multinational
Comments
EU/EFTA Sponsors
Austria
1
2
5
1
9
4
5
Belgium
4
7
1
1
2
15
12
3
Czech Rep
1
2
3
6
6
0
Denmark
6
7
13
14
0
(1 NC)
Finland
1
1
1
0
France
4
4
9
1
3
21
12
9
Germany
1
6
16
1
7
1
3
35
29
7
(1 NC)
Greece
1
1
1
Italy
11
1
3
3
18
16
2
Netherlands
6
1
10
1
1
1
20
5
17
(2 NC)
Norway
2
2
4
4
Poland
1
1
1
Spain
17
4
43
1
6
71
67
5
(1 NC)
Sweden
3
4
5
1
13
11
3
(1 NC)
UK
12
11
16
7
46
34
14
(2 NC)

35.  As of April 2013, the UK had 34 active clinical trials involving stem cells. The majority of these were early phase trials.[70] Figure 2 shows the number of ongoing stem cell therapy clinical trials in the UK.

FIGURE 2

Ongoing stem cell therapy clinical trials in the UK[71]

To illustrate this work, we set out further examples of ongoing UK clinical trials in Box 3 (these supplement the examples in paragraphs 13-17).

BOX 3

Further examples of UK regenerative medicine clinical trials

University College London (UCL) and King's College London are collaborating on a gene therapy phase I clinical trial for graft versus host disease (a disease where transplanted cells try to attack a patient's cells having identified them as "foreign").[72] T lymphocytes (T cells) carried in a graft have powerful beneficial effects and play a vital role in the eradication of leukaemia and in fighting infection, but can also damage healthy tissues and cause graft versus host disease. In this trial, T cells are modified to encode a "switch" so that they can be eliminated or "turned off" if problems arise.[73]


Cell Medica (a UK cell therapy company) is conducting a phase III trial to investigate the potential clinical benefit of a cell therapy in combination with a drug therapy to treat cytomegalovirus (a common viral infection in the herpes family) recurrence in patients following a bone marrow transplant (specifically, in this case, allogeneic haematopoietic stem cell transplant from a seropositive sibling donor).[74]


Industry

36.  Data from the Regenerative Medicines in Europe Project (REMEDiE) (Figure 3) demonstrated that the majority of regenerative medicine companies active in Europe were in the UK, France and Germany.

FIGURE 3

Regenerative medicine companies broken down by European Union Member State[75]

37.  The chart below (Figure 4) allows us to compare the European regenerative medicine industry with the rest of the world and these data shows that, in 2010, Europe and North America had the most companies working in this field.

FIGURE 4

Type of regenerative medicine company broken down by company size and region[76]

38.  On the basis of Office for National Statistics' figures about the pharmaceutical industry, and "assuming an average of 20 employees per company", the UK Regenerative Medicine Community estimated that "regenerative medicine, and regenerative medicine-related, companies contribute around £150 million of production and £80 million gross value added to the UK economy, that is around one percent of current production figures for UK pharmaceutical manufacturing and around 10% of the global cell therapy market".[77] The Scottish Government described a rapid expansion from three companies in Scotland operating in the sector in 2004 to more than 20 companies in 2012.[78] The BIA was of the view that the UK had a complementary mix of cell therapy companies alongside service, tools and technology companies.[79]

39.  Pfizer, a major pharmaceutical company, operates its regenerative medicine activities from its Neusentis Unit in Cambridge, along with a division in the United States of America. These activities focus on age related and degenerative disorders, including collaborative work with UCL and Moorfields Eye Hospital to develop a cell replacement therapy for age related macular degeneration.[80] Amgen, an international small or medium sized enterprise (SME) which discovers, develops, manufactures and delivers innovative human therapeutics, has a base in the UK hosting both commercial and research and development activities. In partnership with UCB Pharma, it is developing a treatment for osteoporosis.[81] Azellon Cell Therapeutics is a spin-out company from the University of Bristol. It is developing a patented platform technology to repair damaged tissue using mesenchymal stem cells.[82] Neotherix, a spin-out from Smith and Nephew based in York, is a regenerative medicine seeking to develop and commercialise scaffolds for tissue regeneration and repair.[83] These examples show the variety of types of company working in this field in the UK.

40.  The following "heat-map" (Figure 5) gives an indication of the spread of regenerative medicine companies within Great Britain by region.

FIGURE 5

Heat map of GB regenerative medicine companies[84]

Funding

41.  The Strategy for Regenerative Medicine in the UK broke down available public funding for regenerative medicine research by technology readiness level (TRL). Each TRL is explained in Figure 6 (overleaf).

FIGURE 6

TRL Stages[85]


42.  In 2012, UK public sector investment in regenerative medicine was over £77 million. This is broken down by agency in Figure 7 below.

FIGURE 7

UK public sector spend on regenerative medicine (£ million)[86]


In addition, significant amounts of money have been set aside for the Regenerative Medicine Platform and Cell Therapy Catapult. We explore these, and other investments in regenerative medicine, in greater detail below.

43.  Figure 8 breaks down the amount of public funding available for regenerative medicine by TRL in 2010 (although it should be borne in mind that TRLs are a guide and not entirely fixed stages).

FIGURE 8

Regenerative medicine spend by TRL stage[87]

BASIC SCIENCE

44.  Seventy-nine percent of public sector funding for regenerative medicine was for basic or early preclinical research in 2010. The research councils primarily fund regenerative medicine basic science through response-mode funding (that is, competitions to identify projects which are excellent).[88]

UK REGENERATIVE MEDICINE PLATFORM

45.  As a result of the taking stock exercise, the Biotechnology and Biological Sciences Research Council (BBSRC), the Engineering and Physical Sciences Research Council (EPSRC) and the MRC jointly established the UK Regenerative Medicine Platform (UKRMP). It is a national programme to promote translational research in the field, and to address knowledge gaps and obstacles where more development is needed to underpin the delivery of new therapeutic approaches.[89]

46.  The UKRMP initially funded the establishment of up to five interdisciplinary research hubs which brought together teams of researchers to address a number of strategically important, tractable translational challenges. These challenge areas were refined from the regenerative medicine community's responses to a scoping call for expressions of interest in the UKRMP. This investment will be up to £25 million over five years. Following this initial round, a call to establish complementary disease-focused research programmes will be launched with an anticipated £5 million or more of funding.[90]

REGENERATIVE MEDICINE PROGRAMME

47.  In 2008-09, the TSB undertook to develop programmes that could support the emergence of new industries. One of those areas was regenerative medicine. The Regenerative Medicine Programme was developed in partnership with the MRC, BBSRC and EPSRC, with the aim of ensuring that UK businesses could achieve a commercially competitive edge with global impact by underpinning and enabling the best regenerative medicine businesses in the UK to flourish; and building a connected regenerative medicine community by forming well-linked programmes of work and activities to develop medicines and technology platforms.[91]

48.  The programme focused on addressing challenges in three areas:

(1)  "Therapeutic Development: to support companies to progress products towards or into the clinic;

(2)  Tools and Technologies: to address manufacturing and safety/efficacy challenges and to build linkages in the supply chain, both business to business and business to academia); and

(3)  Value systems and business models: to allow companies and stakeholders to develop a better understanding of where and how value will be created in the emerging regenerative medicine value chain and develop business models to enable businesses to best capture that value".[92]

49.  The programme funded a total of 76 projects and committed £16.25 million of TSB funding, with additional funding committed by the MRC, the BBSRC, the EPSRC, the Economic and Social Research Council (ESRC) and the Scottish Government. These projects were matched with £7.5 million of funding from industry. Some examples of its efforts included direct financial support to five commercially led projects to start clinical studies, and support to enable Tissue Regenix, a University of Leeds spin-out company, to achieve AIM (the London Stock Exchange's international market for smaller growing companies) listing, which raised £4.5 million.[93] Table 4 summarises how the programme's funding was divided.

TABLE 4

Regenerative Medicine Programme grant funding 2009-11[94]
Theme Number of projects funded Amount of funding (£ million)
Therapeutic feasibility studies 312.8
Therapeutic development stage 1 163.6
Therapeutic development stage 2 41.9
Tools and technologies feasibility studies 121.6
Tools and technologies stage 2 106.6
Value systems and business models 32
Stem Cells For Safer medicine programme (SC4SM) n/a0.5
TOTAL76 19

CELL THERAPY CATAPULT

50.  The Cell Therapy Catapult was established in May 2012. It aims to provide additional resources and expertise to support the emerging industry, and progress therapies to the point where there is sufficient evidence of efficacy, safety, manufacturability, cost effectiveness and market potential.[95] The TSB intends the Cell Therapy Catapult to accelerate the creation of a large (>£10 billion) industry, generating both health and wealth for the UK. It operates as an independent, not-for-profit research organisation and will receive £70 million of core funding over the next five years from the TSB.[96] The Cell Therapy Catapult hopes to leverage at least £10 million a year from grant funders (other than the TSB) and £10 million a year from industry contracts.[97] The work of the Cell Therapy Catapult will be considered further in Chapter 5.

BIOMEDICAL CATALYST

51.  The MRC and the TSB have collaborated to offer funding through the Biomedical Catalyst to SMEs and academics looking to work, either individually or in collaboration, to develop solutions to healthcare challenges. It provides awards for feasibility, early-stage and late-stage research and awards made so far have included regenerative medicine research.[98] For example, ReNeuron (a British stem cell business) has received a £0.4 million grant towards the funding of a UK phase I clinical trial treating patients with limb ischemia (a condition that occurs when blood flow to the limbs is severely restricted from a build up of fat in the arteries) and a £0.8 million grant to fund pre-clinical development of the company's ReN003 stem cell treatment for retinitis pigmentosa.[99]

NIHR

52.  Through Biomedical Research Centres (BRCs) and Units (BRUs), the National Institute for Health Research (NIHR) is funding regenerative medicine to the sum of £9 million a year.[100] Tables 5 and 6 break down NIHR investment in the field of regenerative medicine.

TABLE 5

Biomedical Research Centre funded regenerative medicine research[101]
NHS Organisation Academic Partner Research Themes Funding
2012-17

(£ million)

Cambridge University Hospitals NHS Foundation Trust University of Cambridge Transplantation and Regenerative Medicine 5.4
Great Ormond Street Hospital for Children NHS Trust University College London, Institute of Child Health Stem and Cellular Therapies 11.5
Guy's and St Thomas' NHS Foundation Trust (2 programmes) King's College London Transplantation; Translational Genetics 6.7
Imperial College Healthcare NHS Trust (2 programmes) Imperial College London Surgery and Technology (which includes a component on Cell Therapies) 10.1
Moorfields Eye Hospital NHS Foundation Trust (2 programmes) University College London Gene Therapy; Regenerative Medicine and Pharmaceutics 3.5
University College London Hospitals NHS Foundation Trust University College London Cellular and Gene Therapy 1.5

TABLE 6

Biomedical Research Unit funded regenerative medicine research
NHS Organisation Academic Partner Research Themes Funding
2012-17

(£ million)

Barts & The London NHS Trust Queen Mary University of London Cardiovascular Regenerative Medicine 1.5
University Hospitals Bristol NHS Foundation Trust University of Bristol Cardiovascular Regenerative medicine 1.4
University Hospitals Birmingham NHS Foundation Trust University of Birmingham Liver Regeneration, Repair and Stem Cells 0.6
Leeds Teaching Hospitals NHS Trust University of Leeds Biomaterials and Regenerative Interventions 0.4
Oxford University Hospitals NHS Trust University of Oxford Orthopaedics3.1

THIRD SECTOR

53.  Investment by the third sector in regenerative medicine has been growing over the last five years: over £51 million was invested in regenerative medicine between 2005 and 2010,[102] and average annual investment increased from £6 million in the period 2005-08 to £13 million in 2009.[103] Some examples of third sector funding include the British Heart Foundation's "Mending broken hearts" appeal, which aims to fundraise an additional £50 million for investment in cardiovascular science,[104] Arthritis Research UK's £5.9 million tissue engineering (multi-site) centre, which aims to regenerate bone and cartilage by using patients' own stem cells to repair the joint damage caused by osteoarthritis,[105] and £15 million of funding from the UK Stem Cell Foundation since 2005 for stem cell research projects.[106] The Wellcome Trust awarded £55.4 million related to regenerative medicine in 2011-12. In partnership with the MRC, it has invested £12.75 million to generate and characterise a large number of high quality human induced pluripotent stem cells (iPS cells).[107]

EU FUNDING

54.  The European Commission (EC)'s Seventh Framework Programme (FP) provided a budget of €6.1 billion for health research over the period 2007-13. One facet of this programme has been the Innovative Medicines Initiative (IMI) Joint Undertaking, in partnership with the pharmaceutical industry, which provided €2 billion of funding for research activities to accelerate the discovery and development of better medicines by removing bottlenecks in the development process.[108] The EC contributed €249.6 million to 37 stem cell research projects from 2007-12, through the health and SME streams of FP7.[109] Table 7 shows the breakdown of this funding by project type and year.

TABLE 7

European Commission project funding for regenerative medicine 2007-10[110]
Year Type of project Number
funded
Amount
(
million)
2007Stem cell-based therapies 223.6
2007Culture conditions 720.7
2008Cells and tissues 223.7
2008Biomaterials 333.8
2008Endogenous cells 332.7
2010RM clinical trials 741
2010Tools and technologies 738.1
2012Controlling differentiation and proliferation in human stem cells intended for therapeutic use 636
TOTALn/a 37249.6

55.  In 2012, the Stem Cells for Drug Discovery project (stemBANCC) was launched under the IMI. Its aim is to generate and characterise 1, 500 high quality patient derived iPS cell lines and provide access to them in an accessible and sustainable bio-bank. StemBANCC also aims to demonstrate proof of concept for the utility of induced pluripotent stem cells in drug discovery for hard-to-treat disorders and chronic diseases including diabetes and dementia. The UK is providing the "responsible entity" (leader of the academic and SME participants in the consortium, responsible for the scientific management and the supervision of the overall progress in collaboration with the co-ordinator) for this project, and almost one third of all partners are based in the UK.[111]


54   Department for Business, Innovation and Skills (BIS) and Department of Health (DH): Taking stock of regenerative medicine in the United Kingdom, July 2011. Back

55   ABPI, London Regenerative Medicine Network (LRMN), William James, NHSBTS. Back

56   Health Protection Agency (HPA), Q 4. Back

57   Q 2. Back

58   OSCI. Back

59   BSBMT, BSH, RCPath, BIA, HPA, University of Manchester, OSCI, Parkinson's UK, Professor Stephen Rimmer, Professor Sheila MacNeil and Professor John Haycock, University of Sheffield, Q 67, University College London (UCL) applied regenerative science group. Back

60   LLR. Back

61   British Heart Foundation, Nobel Foundation: The Nobel Prize in Physiology or Medicine, 2007: http://www.nobelprize.org/nobel_prizes/medicine/laureates/2007/. Back

62   Nobel Foundation: The Nobel Prize in Physiology or Medicine, 2010: http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/. Back

63   California Institute for Regenerative Medicine (CIRM). The Nobel Prize in Physiology or Medicine, 2012: http://www.nobelprize.org/nobel_prizes/medicine/laureates/2012/. Back

64   Professor William S. James, University of Oxford. Back

65   RCUK, Q 16, further supplementary written evidence from the Government. Back

66   National Institute for Health Research (NIHR): Understanding clinical trials, October 2010. Back

67   Adapted from NIHR: understanding clinical trials, October 2010. Back

68   Consulting on Advanced Biologicals Ltd. Back

69   Trials registered as such on EudraCT, based on the following article: Maciulaitis, R., D'Apote, L., Buchanan, A., Pioppo, L., Schneider, CK.: 'Clinical development of advanced therapy medicinal products in Europe: evidence the regulators must be proactive', Molecular therapy: the journal of the American Society of Gene Therapy, 2012.
NC = non commercial. 
Back

70   Cell Therapy Catapult: UK Clinical Trials Database, April 2013. Back

71   IbidBack

72   NHS Choices: Bone marrow transplant, 2012: http://www.nhs.uk/Conditions/Bone-marrow-transplant/Pages/Introduction.aspx. Back

73   NIH: Clinical trials database suicide gene therapy trial, 2012: http://clinicaltrials.gov/ct2/show/NCT01204502?term=Dr+Waseem+Qasim&rank=3. Back

74   LRMN, op. cit. UK Clinical Trials Database, NHS Choices: Cytomegalovirus (CMV), 2012: http://www.nhs.uk/Conditions/Cytomegalovirus/Pages/Introduction.aspx, NIH: Regenerative Medicine, 2007: http://stemcells.nih.gov/info/scireport/pages/chapter5.aspx. Back

75   Adapted from REMEDiE: Regenerative medicine in Europe: emerging needs and challenges in a global context, 2011. Back

76   Derived from the REMEDiE project database: http://www.cs.york.ac.uk/satsu/remedie. Back

77   UK Regenerative Medicine Community. Back

78   Scottish Government. Back

79   BIA. Back

80   Pfizer. Back

81   UCB Pharma. Back

82   Azellon. Back

83   Q 283, www.neotherix.com. Back

84   Based on supplementary written evidence from the Government. They identified 40 businesses in Great Britain whose primary purpose was to develop regenerative medicine products. Back

85   Adopted from written evidence from Professor Chris Mason, TSB: Presentation outlining the vision for a Cell Therapy TIC, May 2011, US Department of Defence: Technology Readiness Assessment (TRA) Deskbook, July 2009, and op. cit. Strategy for Regenerative Medicine. Back

86   Supplementary evidence from the research councils. These numbers do not included investment in the Regenerative Medicine Programme (which was only launched during 2012-13) and the level of TSB investment in the Cell Therapy Catapult is significantly lower than it will be in the future given that it was only set up in 2012. ESRC data to be updated when received.
Key: MRC: Medical Research Council; BBSRC: Biotechnology and Biological Sciences Research Council; TSB: Technology Strategy Board; ESPRC: Engineering and Physical Sciences Research Council; ESRC: Economic and Social Research Council; NIHR: National Institute for Health Research. 
Back

87   MRC, BBSRC, EPSRC, ESRC and TSB: A Strategy for UK Regenerative Medicine, March 2012. Back

88   RCUK. Back

89   TSB. Back

90   RCUK. Back

91   TSB. Back

92   IbidBack

93   Ibid. Back

94   IbidBack

95   Cell Therapy Catapult. Back

96   Q 285. Back

97   TSB, Cell Therapy Catapult and presentation by its Chief Executive: https://catapult.innovateuk.org/documents/10726/0/CEO+AMC+FINAL.pdf/45ee556a-dd9d-4c01-88fe-6c889e633331. Back

98   RCUK, TSB. Back

99   ReNeuron press release: ReNeuron wins two major Biomedical Catalyst grants to pursue core stem cell therapy programmes-aggregate award of £1.2 million for UK phase I clinical trial in critical limb ischaemia and UK late pre-clinical development of therapy for retinitis pigment, 2013. Back

100   Q 43. Back

101   Further supplementary written evidence from the Government. Back

102   UK Stem Cell Foundation. Back

103   Association of Medical Research Charities. Back

104   Q 46. Back

105   Arthritis Research UK. This figure includes contributions from the participating universities. Back

106   UK Stem Cell Foundation. Back

107   RCUK. Back

108   European Commission: Health research in FP7, 2011. Back

109   Presentation by Charles Kessler of the European Commission Research and Innovation DG: EU Support to Stem Cell Research, 2011, and correspondence. Back

110   Ibid. Back

111   Further supplementary written evidence from the Government, http://stembancc.org/index.php/partners/. Back


 
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