Laying the Teva foundations

1900 - 1960
Laying the Teva foundations
The first company that later grew to be Teva Pharmaceutical Industries was established in Jerusalem in 1901. Three pharmacists started to work together in delivering medication to customers. They expanded and as a small business start distributing imported medications throughout the land.
And in 1935 Teva opened a first small drug factory after which additional drug factories were launched. At the time the company said: We wish to
assist human nature by means produced (extracted) from Nature. That is why the name Teva, which is Hebrew for “nature”.
The founding of Teva in Israel
The first company that later grew to be Teva
Pharmaceutical Industries is established in
Jerusalem in 1901.
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1912
1902
1930s
Georg Schöne determines that skin homografts
always fail and that subsequent grafts from
the same donor fail more rapidly than the first.
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1920s
Leo Loeb determines that the strength and
timing of rejection of skin homografts in
rats was governed by the extent of genetic
disparity of donor and recipient and shows
involvement of lymphocytes.
1936
1954
First successful kidney
transplantation
J. Murray, Peter Bent Brigham Hospital, Boston,
performs a live kidney transplantation between
23-year-old identical twins, one of who is
dying from advanced glomerulonephritis. The
recipient dies 8 years later for pneumonia.
Source
First human-to-human
kidney transplant
Yuri Voronoy, Russian surgeon performes the
first human-to-human kidney transplantation,
using a kidney from a cadaver donor of B+ blood
type to a recipient of O+ blood type.
British zoologist Peter Medawar uses experimental skin transplants on animals to explain
why burn victims reject donated skin.
Source
Discovering the role
of the lymphocyte
Source
Medawar’s ground-breaking
work in immunology
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Source
James Murphy establishes conclusively the role of
the lymphocyte in tissue and tumor graft rejection
and in protection against infection. Contemporary
mainstream immunology pays little attention to
these findings, until the lymphocyte will be
“rediscovered” with the advent of modern
cellular immunology after the mid-1950s.
Defining time-lapse
Source
1940s
German scientist Dr. Karl Landsteiner
classifies blood into three groups
A, B and O, and his colleagues add
a fourth, AB. He will be rewarded
the Nobel Prize in 1930.
Skin grafting
Source
Blood groups A, B, O, AB
discovered
Source
1950
Blood cell types
Ray Owen (University of Wisconsin, USA) finds
that in cattle fraternal twins frequently have a
mixture of two red blood cell types.
Source
HQ/MULTI/13/0003a
1901
1940s
Medawar’s ground-breaking
work in immunology
B
uilding upon observations of the immune system
dating back thousands of years, British zoologist
Peter Medawar uses experimental skin transplants on animals to explain why burn victims
from the bombing of civilians in England during World War II
reject donated skin. His work sets the stage for a new field,
transplantation biology. Medawar would later earn the Nobel
Prize for his work.
Medawar’s earlier research, done at Oxford, was on tissue culture, the regeneration of peripheral nerves and the
mathematical analysis of the changes of shape of organisms
that occur during this development. During the early stages of
the Second World War he was asked by the Medical Research
Council to investigate why it is that skin taken from one human
being will not form a permanent graft on the skin of another
person, and this work enabled him to establish theorems
of transplantation immunity which formed the basis
of his further work on this subject. When he moved
to Birmingham in 1947 he continued to work on it,
in collaboration with R. Billingham, and together
they studied there problems of pigmentation
and skin grafting in cattle, and the use of skin
grafting to distinguish between monozygotic and
dizygotic twins in cattle. In this work they took
into consideration the work of R. D. Owen and
concluded that the phenomenon that they called
«actively acquired tolerance» of homografts could
be artificially reproduced.
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Source
HQ/MULTI/13/0003
Peter Medawar skin grafting a cow.
The unexpected acceptance of
grafts exchanged between chimeric
bovine fraternal twins was the key
to understanding tolerance.
(The photograph is a gift from the
private collection of Rupert Billingham, who was the photographer.)
HQ/MULTI/13/0003a
Source
1960 - 1980
1960s – 1970s: Exploring global opportunities
Small factories, struggling to survive, decide to merge for increased efficiency. In 1976, Eli Hurvitz works at Teva. He had already put some companies together (namely Assia, Zori and Teva {the Hebrew word for ‘Nature’} ) to form Teva Pharmaceutical Industries Ltd., at that time the largest
healthcare company locally. And Eli Hurvitz becomes the leader who spurs the international expansion. In pursuit of greater capabilities in the
areas of research, development and marketing, Teva begins to acquire smaller pharmaceutical firms around the world.
First successful
liver transplantation
Dr. Thomas Starzl, University of Colorado Hospital, performs the first successful liver transplant;
the liver functions for thirteen months. Starzl is
also the first to use a combination of Azathioprin
and Steroids as immunosuppression.
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1967
Source
First successful
human heart transplant
“It’s going to work!” Dr. Christiaan Barnard
shouts as the heart of Denise Darvall,
a 23-year-old woman who died in an
automobile accident, begins to beat in the
chest of 54-year old Louis Washkansky.
Learn more
1980
1967
Source
1968
Learn more
Source
First successful
liver transplant in Europe
Roy Calne, a pioneer in organ transplantation
performs the first liver transplant in Europe at
Addenbrookes Hospital, Cambridge, UK.
Source
The Nobel Prize in Physiology or Medicine
1980 is awarded jointly to Baruj Benacerraf,
Jean Dausset and George D. Snell “for their
discoveries concerning genetically determined
structures on the cell surface that regulate
immunological reactions”.
Jean Dausset
Prof. Dr. Jon J. van Rood, a young physician
from Leiden proves that matching the HLAtype of donor and recipient has a positive effect
on the outcome of transplantation. In 1967 he
founds Eurotransplant starting with 12 centers
in three countries. The patient oriented allocation of organs leads to spectacular outcome
improvement.
Source
Nobel Prize for work
in immunology
Baruj Benacerraf
Foundation of Eurotransplant
George D. Snell
1970s
Researchers discover new
compound for transplant drug
Researchers discover that ciclosporin, a compound produced by fungi found in a soil sample
obtained in 1969 from Hardangervidda, Norway,
can suppress the human immune system. Years
of tests reveal that given as part of a regimen
primarily with steroids, it selectively suppresses
T-cells and can prevent the rejection of transplanted organs.
Source
HQ/MULTI/13/0003a
1967
1970s
Researchers discover new compound
for transplant drug
R
esearchers discover that ciclosporin, a compound produced by fungi found in a soil sample obtained in 1969 from Hardangervidda,
Norway, can suppress the human immune
system. Years of tests reveal that given as part of a regimen
primarily with steroids, it selectively suppresses T-cells and
can prevent the rejection of transplanted organs.
With the discovery of ciclosporin in 1971 begins a new era
in immunopharmacology. It is the first immunosuppressive
drug that allowes selective immunoregulation of T-cells
without excessive toxicity. Ciclosporin is isolated from the
fungus Tolypocladium inflatum and is first investigated as an
anti-fungal antibiotic but its spectrum is too narrow to be of
any clinical use. H. F. Stähelin and J. F. Borel, both working
for Sandoz, discover its immunosuppressive activity in
1976. This leads to further investigations into its properties
involving further immunological tests and investigations into
its structure and synthesis. Ciclosporin has unwanted side
effects, notably nephrotoxicity, but animal testing shows
ciclosporin to be sufficiently non-toxic to begin clinical trials.
These initially fail due to poor absorption of the drug. Once
this is overcome, results are encouraging enough for ciclosporin to be licensed for use in clinical practice. Ciclosporin
changes the face of transplantation. It decreases morbidity
and enables the routine transplantation of organs.
Source
HQ/MULTI/13/0003a
Source
1980 - 1990
1980s: A decade of growth
The acquisitions by Teva in this era mark the start of even sharper growth. First the acquisition of local drug manufacturer Ikapharm along with
API producer Plantex enables the (separate) production of Penicillin and non-Penicillin drugs. This split of production, an essential requirement
of USA health authorities, paved the way for Teva’s entry into the US market. Teva also expands its activity in the field of medical devices by
acquiring 50% of Migada, and further expands its US market share by forming partnerships with W.R. Grace and Lemmon. Acquiring companies
Abic and Travenol turns Teva into Israel’s largest and most successful pharmaceutical company and the flagship of the Israeli Industry.
First successful heart-lung
transplant
The first successful heart-lung transplant
takes place at the Stanford University Medical
Center; the surgeons are Dr. Norman Shumway
and Dr. Bruce Reitz.
1983
Source
1987
Source
1988
Teva Opava, CZ
The Food and Drug and Administration approval
of ciclosporin opens the door to the modern
era of organ transplantation. What had been a
marginally successful, experimental treatment or just plain impossible - becomes routine.
New transplant drug
discovered
Scientists develop FK506 or tacrolimus, a
macrolide derived from the bacterium streptomyces tsukubaensis, found to be an immunosuppressive drug more potent than ciclosporin.
Both drugs have a similar mechanism of action.
Teva (Galena, CZ) starts
producing Ciclosporin
Sandimmune® oral solution
approved by FDA
Source
1988
FDA approves organ
preservation solution
FDA approves a solution that extends preservation time for livers and other organs. UW
solution is the first designed solution for organ
preservation instead of using cold solutions like
lactated Ringer solution.
Source
When Ciclosporin is introduced in the market
it is still the time of “the cold war” and “the
iron curtain” in Europe. Patients behind the
iron curtain do not have access to this new
drug. In that time the Czech pharmaceutical
company Galena (later Teva) develops a ciclosporin product for patients in the Eastern
European countries. A first successful product is launched in 1990, the oral solution
named Consupren.
HQ/MULTI/13/0003a
1981
1987
New transplant drug discovered
T
acrolimus (FK 506) is a 23-membered macrolide
lactone discovered in 1984 while testing a wide
range of fermented broths of a Japanese soil
sample that contain the bacteria Streptomyces
tsukubaensis. FK 506 is found to be an immunosuppressive
drug more potent than ciclosporin. Both drugs have a similar
mechanism of action though different chemical structure.
The name tacrolimus is derived from Tsukuba macrolide immunosuppressant.
It is Thomas Starzl and co-workers in Pittsburgh who believe
in the substance and present first “most exciting” results at
the ESOT Congress 1987 in Gothenburg. Four years later he is
convinced that “… the clinical use of this drug will permit or
contribute to the next plane of achievements in transplantation”.
It is first approved as Prograf® (Astellas) by the Food and
Drug Administration (FDA) in 1994 for use in liver transplantation. Today tacrolimus is seen as the gold standard for
prophylaxis of transplant rejection in liver, kidney or heart
allograft recipients. It is mainly used in combination with
steroids and mycophenolate mofetil.
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Source
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1990 - 2000
1990s: Innovation becomes our nature
Teva turns into a major international player by adopting an aggressive merger and acquisition strategy in the USA and in Europe. During the
1990s, Teva also opens its flagship API plant Teva-Tech and completes ten years of intensive innovative R&D activities with the successful launch
of several products, of which Copaxone is a striking example, bringing better lives to MS patients worldwide, including successful patient service
programs. The foundation for Teva Transplant is laid as Galena, a company not yet part of Teva, in the Czech Republic, develops ciclosporin for the
countries behind “the Iron curtain”.
1990
Dr. Murray awarded
Nobel Prize
Joseph E. Murray shares the Nobel Prize
in Physiology or Medicine in 1990 with
E. Donnall Thomas for their discoveries
concerning organ and cell transplantation
in the treatment of human disease.
Learn more
1994
1991
A large group of pathologists, nephrologists, and
transplant surgeons meet in Banff, Canada and
in 1993 the first Banff classification for assessment of renal allograft biopsies is introduced
as a standardized international classification of
renal allograft pathology and acute rejection.
Source
FDA approves Tacrolimus
(Prograf® Astellas)
Tacrolimus is first approved as Prograf®
(Astellas) by the FDA in 1994 for use in liver
transplantation. Today tacrolimus is seen as
the gold standard for prophylaxis of transplant
rejection in liver, kidney or heart allograft
recipients. It is mainly used in combination
with steroids and mycophenolate mofetil.
Learn more
1995
First successful laparoscopic
live-donor nephrectomy
Drs. Lloyd Ratner and Louis Kavoussi, are
the first to perform laparoscopic live donor
nephrectomy at Johns Hopkins, Baltimore.
When compared to the conventional open
donor surgical technique, laparoscopic donor
nephrectomy results in significantly less post
operative pain, a shorter hospital stay, earlier
return to work and daily activities, a more
favorable cosmetic result and with recipient
outcomes identical to the open procedure.
Source
FDA approves Mycophenolate
mofetil (MMF, CellCept® Roche)
MMF is the prodrug to MPA (mycophenolic
acid) that was first mentioned in 1896 but only
developed for the prevention of organ transplant
rejection nearly a century later. MMF is used in
place of Azathioprine.
Source
1995
The first Banff
Classification meeting
Source
1997
Successful
knee-transplantation
First successful allogeneic vascularised
transplantation of a fresh and perfused
human knee joint by Gunther O. Hofmann.
Source
Source
First successful hand
transplantation
Prof. Hakim and Prof. Dubernard (Lyon, France)
perform the first hand transplantation. Feeling
uncomfortable with the transplanted hand the
recipient is non-compliant with immunosuppression and physiotherapy what leads to
rejection episodes and at his own request
the transplant is removed in 2001.
Source
FDA approves Sirolimus
(Rapamune®)
Being originally developed as an antifungal
agent, Sirolimus (rapamycin) is approved
as the first mTOR inhibitor to be taken with
ciclosporin and corticosteroids for prevention
of organ rejection in patients receiving kidney
transplantation.
Source
HQ/MULTI/13/0003a
1998
1999
K Solez and LC Racusen: Banff classification revisited
potential categories of rejection that would be clinically
relevant for guiding therapy.
The new classification used lesion scoring and guidelines
to provide rigor in the evaluation of renal allograft pathology
and the assignment of biopsies into diagnostic categories.
Nonrejection pathology in the allograft was also considered
and described in some detail, and this continues to be a focus
in ongoing Banff meetings.
THEMES OF THE BANFF MEETINGS
A previous article on the history of the Banff Classification
focused on the participants.1 Here, we will concentrate on the
ideas espoused by the Banff meetings (Table 1) and the Banff
Articles
70
60
50
40
30
20
10
0
Banff articles
19
9
19 1
9
19 2
9
19 3
9
19 4
9
19 5
9
19 6
9
19 7
9
19 8
9
20 9
0
20 0
0
20 1
0
20 2
0
20 3
0
20 4
0
20 5
0
20 6
0
20 7
0
20 8
0
20 9
1
20 0
1
20 1
12
The first Banff Classification meeting
Banff articles per year
Figure 1 | Number of Banff articles in transplantation per year.
The peak of 73 articles in 2005 was the combined effect of increasing
interest in antibody-mediated rejection and viral disease, and the
controversy surrounding the term ‘chronic allograft nephropathy’.
The distribution into categories was Kidney-Clinical (human) 611,
Kidney-Experimental 40, Liver-Clinical (human) 48, Liver-Experimental
8, Pancreas-Clinical (human) 4, All Organs-Clinical (human) 2,
Composite Tissue-Clinical (human) 3, and Heart-Clinical (human) 1.
There are 38 articles thus far in 2012 to July 31, which extrapolate to
65 for the year making 2012 the second highest year for Banff articles.
From the small beginnings in 1991, the Banff working classification has grown to be a major force for setting standards in renal
transplant pathology, and is widely used in international clinical trials of new antirejection agents. The Banff meetings have
expanded from renal allograft pathology to most other areas
of solid organ transplantation, and increasingly incorporate
international working groups, so that productive collaborative
activity is ongoing, creating an important dynamic process
enhancing clinical success in transplantation.
Source
“Combining gene expression
and microscopic analysis, in
my opinion, will be the most
potent approach to diagnosis
in the future.”
from an AJT Editorial
by Robert Colvin
Table 1 | Banff Allograft Pathology Meetings since 1991 with key themes
Location
Length
(days)
Links
Key subjects debated
1991
1993
1995
Banff, Canada
Banff, Canada
Banff, Canada
1.5
3
4
ISN
ISN, CAP
ISN
1997
Banff, Canada
5
ISN
1999
Banff, Canada
5
ISN, NKF, NIH
2001
2003
5
4
ISN, NKF
ISN, NKF
2007
Banff, Canada
Aberdeen,
Scotland
Edmonton,
Canada
La Coruna, Spain
Classification established, lesion scoring, diagnostic categories, physician-led consensus
Liver classification, chronic rejection, first presentation on molecular pathology approaches
Pancreas classification, glomerulitis, first international medical meeting on CD-ROM, first
Banff conference with microscope sessions. Lesion scoring normalized with CADI.
Merging of Banff and CCTT classifications, establishing basis for current Banff classification,
post-transplant lymphoproliferative disorder, first Banff conference with posters
Protocol biopsies, chronic rejection, and viral diseases, clinical practice guidelines.
First conference supported by an NIH grant.
AMR, donor biopsies, genomics, CAN, heart transplantation
C4d, macrophages, tolerance, accommodation, immunodepletion
2009
2011
2005
6
NKF
6
UofA
Banff, Canada
5
UofA
Paris, France
5
UofA
Genomics and molecular markers, B cells, chronic allograft injury with elimination of CAN,
establishment of criteria for chronic rejection
Protocol biopsies, transcriptome, mechanisms of rejection, ptc grading, new total
inflammation score; working groups for v-lesion, genomic integration, pancreas and
composite tissue rejection schemas
Viruses, quality assurance, AMR in kidney, heart, and pancreas, liver allograft
accommodation, endothelial cells, surrogate markers. Working groups.
Sensitized patient, C4d, isolated v-lesion, the future, genomics, glomerulitis, epithelial injury/
epithelial mesenchymal transformation, operational tolerance monitoring in liver grafts
Abbreviations: AMR, antibody-mediated rejection; CAN, chronic allograft nephropathy; CAP, Canadian Association of Pathologists, and Future of Pathology/Laboratory
Medicine in Canada Consortium; ISN, International Society of Nephrology; NKF, National Kidney Foundation (US); NIH, National Institutes of Health (US); ptc, peritubular
capillary; UofA, University of Alberta.
202
Kidney International (2013) 83, 201–206
Source
from Solez K; The Banff classification revisited;
Kidney International(2013) 83:201-206.
Limitations:
The future?
•
•
•
•
•
•
•
•
Lesiongradingissemiquantitative
Reproducibilityoflesionscoring
Reproducibilityisinfluencedby
biological variability
Experienceofthepathologist
Lackofformalincorporationof
morphometry and molecular and
genomics approaches
Adaptionofmorphometry
Integrationofgenomics?
Integrationofmolecular
medicineparameters?
Adapted from Solez K; The Banff
classification revisited; Kidney
International(2013) 83:201-206.
HQ/MULTI/13/0003
I
nspired by the development of a consensus grading system for diagnosis of rejection in cardiac
allografts a working group of renal pathologists,
nephrologists and transplant surgeons meet in
August 1991 to develop a schema for international standardization of nomenclature and criteria for the histologic diagnosis of
renal allograft rejection.
consensus process. The flavor of the Banff meetings from the
beginning was one of flexibility and openness to the ideas of
others. At the original meeting of 20 people in 1991, the
kidney transplant pathology classification that emerged was
very different from any of the drafts that individuals had
created before the consensus discussions began. It was a true
creation of the meeting itself, based on international
expertise, the existing literature, and facilitated discussions.
The classification was designed as a dynamic working
document that could be modified as the need for future
changes was demonstrated.
At the second meeting in 1993, a similar effort was
initiated to create a classification for liver transplant
pathology, and this became a major focus of the Third Banff
Conference held in July 1995.4 The third conference had four
times as many attendees as the first conference and was
conducted with an air of positive expectation that could not
have been anticipated in 1991. The 1995 meeting also
brought Banff lesion scoring into line with the CADI scoring
system,7 so there was no difference between the two
classifications.
By the time of the 1995 meeting, the original Banff
Classification of Renal Allograft Pathology was in wide use,
and there had been extensive studies showing its clinical
validity and reproducibility.8–12 Extrapolating from these
studies, it seemed likely that the classification had already
resulted in improvement in patient care. The Banff
classification had been endorsed by the FDA and other
regulatory agencies, and had enabled the use of objective
histological endpoints for international clinical trials of new
antirejection agents and other scientific studies, a process that
continues to this day.
HQ/MULTI/13/0003a
1991
mini review
2000 - 2010
2000s - 2010s: Continuing to expand our worldwide presence
Teva becomes the largest generic pharmaceutical company, and one of the top 15 pharmaceutical companies in the world. Teva has established
international presence with major manufacturing and marketing facilities in Israel, Europe and the US and through a network of international
subsidiaries. Teva Transplant slowly expands and in 2010 the introduction of Myfenax® is achieved throughout Europe.
In 2003 IVAX Pharmaceuticals Czech Republic
(today Teva Pharmaceuticals), starts the Transplant
Academy, an educational program of science
focused presentations by a panel of expert speakers
complemented by interactive workshops. The first
one takes place in Prague and is organized together
with the Czech Transplantation Society and this
tradition is carried on in collaboration with other
medical societies like Descartes (ERA-EDTA) and
ESOT. In 2013 the 10th anniversary of the Teva
Transplant Academy will take place in Amsterdam,
Netherlands, where the Teva Europe headquarters
is situated.
Learn more
2007
In what doctors call “an unfortunate traumatic
accident,” a 44-year-old Chinese man lost all
but the last half-inch of his penis. To replace it,
they offer him the 4-inch member of an anonymous 22-year-old brain-dead patient whose
parents agreed to donate the organ. The surgery
is performed at Guangzhou General Hospital,
China and later reversed after 15 days because
of severe psychological problems experienced
by the man and his wife.
Source
2008
Ekberg et al publish the
ELITE-Symphony study
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Source
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2008
First successful transplantation
of near total area of face
n engl j med 357;25
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Learn more
Source
2563
First transplant of a human
windpipe using a patient’s
own stem cells
A Colombian woman receives a trachea transplant using her own stem cells so her body
would not reject the transplant. In a Barcelona hospital Paolo Macchiarini and colleagues
plant stem cells from Claudia Castillo, into a
trachea taken from a cadaver. Doctors say the
new windpipe is “almost indistinguishable”
from the patient’s normal bronchi.
Source
A 45-year-old woman with a history of severe
midface trauma undergoes near-total face transplantation in which 80% of her face is replaced
with a tailored composite tissue allograft, by
Maria Siemionow (Cleveland, USA). 6 Months
after surgery, the functional outcome is excellent.
In contrast to her status before transplantation,
the patient can breathe through her nose, smell,
taste, speak intelligibly, eat solid foods, and
drink from a cup.
First successful complete
full double arm transplant
A team of the Technical University of Munich,
Germany conducts the world’s first double-arm
transplant on a 54-year-old farmer who had lost
both his arms in an accident.
This study (the largest trial in transplantation
with 1654 patients included) evaluated the
efficacy and relative toxic effects of four immunosuppressive regimens. The results favour
a reduced exposure to calcineurin inhibitors in
renal transplantation.
The
First successful human
penis transplant
Learn more
2009
Tony Huesman dies after 31
years being heart transplanted
Tony Huesman, the world’s longest living heart
transplant recipient, dies of cancer having survived for 31 years. Huesman received a heart in
1978 under heart transplant pioneer Dr. Norman
Shumway. He dies of complications from cancer,
says his wife, Carol Huesman. He was 51.
“His heart held up to the end,” she says.
Learn more
Source
HQ/MULTI/13/0003a
2003
2006
Teva Transplant Academy
2008
First successful complete
full double arm transplant
A
team of 40 physicians and nurses lead by E.
Biemer, C. Höhnke, H.-G. Machens and M. Stangl
(Technical University of Munich, Germany) conducted the world’s first double-arm transplant on
a 54-year-old farmer who had lost both his arms in an accident.
The medical staff was divided into five teams for the marathon
operation. Two teams each removed one arm from the donor,
while two others prepared the patient to receive them.
The fifth team removed veins from the donor which had to be
taken as part of the transplant to allow for a better blood flow.
Professor Biemer said the surgeons then joined the bone of
the donor’s upper arm to the patient’s shoulder sockets before
connecting arteries and veins. Although the nerve casings
were successfully transplanted as well, new nerves have to
grow.
Transplantation of about 20% of skin surface as well as bone
and bone marrow requires an intensified immunosuppressive
protocol and monitoring. The patient is of risk not only of host
versus graft rejection but also graft versus host disease.
HQ/MULTI/13/0003
HQ/MULTI/13/0003a
Source
2010- 2011
2010 – 2011: Becoming a multinational diversified organization
After the August 2010 acquisition of the German ratiopharm Teva’s market share in Europe increases significantly, but still Teva is looking at new
opportunities: Teva expands into the self-medication channel through the PGT joint venture with Procter & Gamble. This joint venture will increase
the share in self-medication Brands, like Vicks, used by many people.Teva Transplant starts to build the portfolio from 2010, from having Equoral®
in countries across Europe and countries around the world since the 90s, into a portfolio of the most important products for the treatment of
transplant patients.
Myfenax® is available
throughout Europe
Myfenax (mycophenolate mofetil) is now available in all European countries. Myfenax is the
second product from Teva Transplant to reach
the European market. Myfenax, first introduced
in central Europe, is in November available all
over Europe.
2010
2010
First full facial transplant
Source
Source
2010
First double leg transplant
In July 2011 Dr Cavadas and team (Valencia’s
Hospital La Fe, Spain) perform a world-first
double leg transplant on a 20-year old male
amputee. The double leg transplant took 10
hours to perform. In June 2013, the patient
encounters an illness which “forced the man
to stop taking anti-rejection drugs”…
Learn more
2011
Scientists announce that they have created
a functional synthetic genome. They had
computer calculated a DNA sequence, which
was produced in the lab and introduced in the
emptied nucleus of a yeast cell. Thus, the first
cells with a parent being the computer.
The First full facial transplant is done by the
team of Dr Joan Pere Barret (Vall d’Hebron
University Hospital on July 26, 2010 in
Barcelona, Spain.) A man injured in a shooting
accident receives the entire facial skin and
muscles - including cheekbones, nose, lips
and teeth - of a donor.
Learn more
2011
Scientists made ‘artificial life’
Source
Tacni® (tacrolimus) is launched in Europe
as the third product from Teva Transplant.
With Tacni available, the gold standard
regimen at this time is available in Teva
Transplant products: Tacni + Myfenax + steroids. With this step Teva Transplant
is coming closer to its dream to become
a partner of choice for the transplant
community in the (near) future.
Source
In 17 November researchers at CERN trap 38
anti-hydrogen atoms for a sixth of a second,
marking this the first time in history that humans
have trapped antimatter. The big issue is to
capture “the matter”. This is done in a magnetic
field, because positrons and anti-protons have
a charge and can be trapped in an electric field,
but atoms do not.
Source
Source
Tacni® is launched in
countries in Europe
Learn more
Antimatter trapped first time
2011
First artificial organ transplant
On 7 July scientists announce the world’s first
artificial organ transplant has been achieved,
using an artificial windpipe coated with stem
cells. Scientists in London created an artificial
windpipe which was then coated in stem cells
from the patient. Crucially, this technique does
not need a donor, and there is no risk of the
organ being rejected.
Learn more
Source
HQ/MULTI/13/0003a
2010
2010s
Teva establishes range of branded generics
The benefits of scale, that being part of a global
organisation affords, while maintaining agility and
dynamism, mean that Teva Transplant is well placed
to achieve this vision and endeavours to do so for
the long run.
Moreover, Teva Transplant’s commitment is not dependent on patents. We are committed to transplant.
Here to stay.
Teva Transplant aims to have the optimal portfolio of
products and services that could be of benefit in the
treatment of transplant patients. We already have
an extensive range of products for treating transplant
American Transplant Congress 2011: Abstract# 1095
patients comprising the major molecules:
tacrolimus = Tacni
ciclosporin = Equoral and Ciqorin
mycophenolate mofetil = Myfenax
steroids = generic brand
other drugs like epo, statins, blood pressure
agents, antibiotics, etc.
We strive to offer more than the current gold
standard regimen. Here to stay.
Teva’s dynamic team of Transplant Account Managers, supported by a Team-Lead, a Medical Director,
and Head of Transplant Business, ensures that the
Transplant Community is well served and receives
the most efficient and focused support. A pan-European team, aligned with international cooperative
groups and consortia. We are here for the patients
and their wellbeing. Here to stay.
Here to stay.
HQ/MULTI/13/0003a
Teva Transplant’s vision is to become an indispensable partner to the transplant community with which
to collaborate to improve outcomes for patients.
2012 - 2013
2012 – 2013: Teva enjoys both a strong brand image and a reputation for quality
Teva strengthens its long term strategy to diversify and expand its portfolio of branded and specialty pharmaceuticals, sold in over 50 countries.
Teva cares for an innovative pipeline, while making sure the foundations in the (branded) generic and self-medication areas are well cared for as
well. Teva Transplant develops the vision to become a one-stop-shop for the transplant community, and in parallel the strategy to become a partner of choice in the future; collaborative projects with several parties like ESOT, ERA-EDTA, and others are developing and more will be started.
Prototype bionic eye
On August 31 Researchers announced the
successfully performed the first implantation
of an early prototype bionic eye with 24
electrodes. This early prototype consists of
a retinal implant with 24 electrodes. A small
lead wire extends from the back of the eye
to a connector behind the ear. An external
system is connected to this unit in the laboratory, allowing researchers to stimulate the
implant in a controlled manner in order to
study flashes of light “seen” by the lady who
underwent the implantation to help further
research.
Learn more
2013
Source
2013
Ciqorin* was developed to have a Teva
ciclosporin product available in all European
countries, so transplanted patients will have
a quality ciclosporin choice all over Europe.
*registered in Austria as Vanquoral.
2013
First successful urgent lifesaving entire face transplant
2013
Source
Learn more
2013
Establishing the European
Teva Transplant Team
Teva Transplant recognises the need for international collaboration across Europe in the
transplant community. Collaboration across
boarders will in the end be in the advantage to
patients through the advances in the sciences.
To align the structure in Teva to this growing
need the European Transplant Account team
is established, to serve the needs for the European Transplant Community.
Woman pregnant after
uterus transplant
The first woman to receive an uterus
from a donor is now pregnant, her
doctors announced in Turkey early
April. Doctors waited 18 months
after Derya Sert’s uterus transplant
in August 2011 before they implanted
an embryo on April 1 using Sert’s
own egg.
Face transplants are complicated and rare procedures that require extensive preparation of
the recipient over a period of months or years.
But medical officials said the Polish patient’s
condition was deteriorating so rapidly that a
transplant was seen as the only way to save his
life. It was also Poland’s first face transplant.
Learn more
Ciqorin first launches in
Europe
Ear produced using 3D printing
American scientists use a 3D printer to create
a living artificial ear from collagen and ear cell
cultures. In the future, such ears could be grown
to order for patients suffering from ear trauma
or amputation.
Learn more
2013
Source
Source
Discarded kidneys can be used
to generate new kidneys
Researchers at Wake Forest Baptist Medical
Center in the USA find that human kidneys
discarded for transplant can potentially serve
as a natural “scaffolding material” for manufacturing replacement organs in the lab using
regenerative medicine techniques.
Source
HQ/MULTI/13/0003a
2012
2012 - 2013
Source
Source
HQ/MULTI/13/0003a
Source
> 2014 The Next Step
2014 – Beyond
Teva will have grown to become a pharmaceutical global leader. We continue to grow and improve, always moving ahead towards an exciting
future of new challenges and outstanding accomplishments.Teva Transplant continues to expand the portfolio in line with the vision to become a
one-stop-shop option for the transplant community; further work will be done in partnering with the players in this community and beyond, added
services to the portfolio which can support physicians, nurses and patients in order to improve patients’ lives.
Can 3-D printers produce
human embryonic stem cells?
Using stem cells as the ink in a 3-D printer, researchers in Scotland
hope to eventually build 3-D printed organs and tissues. A team at
Heriot-Watt University used a specially designed valve-based technique
to deposit whole, live cells onto a surface in a specific pattern.
Source
Having our very own lab-grown organs?
We are in the midst of the biotechnology revolution, the benefits of
which are finally starting to appear. Personalized medicine will emerge
in the coming decades, where physicians will be able to prescribe
medicines tailored specifically to our genetic constitutions. Biologists
are also exceedingly close to being able to generate differentiated tissue from our very own stem cells. This will eventually allow us to grow
our very own organs, including the heart — no donors needed, and with
virtually no chance of rejection.
The future
Surely everyone has thought about
the future once in a while.
30 Years ago transplantation became
routine by the introduction of ciclosporin.
However we are still facing a lack of organs
and a long term graft outcome that has not
significantly improved.
30 Years from now - will robots do a
transplantsurgery?Willwegrowourown
organsfromourowntissue?
The future - nobody knows but some of the
outstanding people in transplantation are
willing to share their thoughts on the next
panel.
Disclaimer: These future perspectives are provided
by the past, current and future ESOT Presidents and
Organising committee Presidents, on a voluntary basis.
Between the Presidents and Teva Transplant no financial
obligations exist and the Presidents and Teva are not
necessarily supporting each other’s vision or opinion.
HQ/MULTI/13/0003a
What’snext?
2050s
The Next Step
‘There will be a revolution in the
preservation and reconditioning
of organs’
‘In 2050 engineered organs that
produce urine and bile are available
for transplantation’
‘I am certain that transplantation will
remain a fascinating field over the next
few years and for much longer. In 2050
I am certain that we will look back and
say “Do you remember the time when we
simply kept organs on ice” i.e. there will
be a revolution in the preservation and
reconditioning of organs. In addition
I think that the advances in stem cell
therapy, combined with nanotechnology
and 3-D printing, will further revolutionise
our discipline. Yet the challenges of medical ethics will continue in our
exciting specialty. I warmly recommend this branch of medicine/surgery.’
‘Laboratories will seed stem cells of a
patient with a malfunctioning organ
into organ scaffolds that will grow into
a perfect functioning human organs.
‘To date, the Achilles’ heel in transplantation is not rejection but the
persistent shortage of donor organs’
‘With novel in- and ex-situ perfusion
technologies including addition of pharmacological and biological agents older
and highrisk organs can be repaired and
reconditioned, changing un-transplantable to transplantable with improved
outcomes for our patients.’
Rutger J. Ploeg
Past-president of ESOT
Carla Baan
President of ESOT
‘No doubt, the future of ‘Earth
Inc.’ will be (to) transplantation’
‘When in 1951 the first kidney transplant
was performed, human existence was
changed profoundly. Indeed a human
being would not die anymore with the
same organs she or he was born with! In
2050, exactly one hundred years later,
the interplay between advanced information technology, transplantation and
regenerative medicine will have even
more profoundly changed mankind. Different tissues, cells and organs originating from different (manipulated) organ donors and/or constructed in
the laboratory will function within the same person. ‘Puzzle people’
will overrule the actual world demography... And many transplant
professionals of all kinds of specialisations will be needed to bring
this endavour to a good end. No doubt, the future of ‘Earth Inc.’ will
be (to) transplantation.’
Professor Jan Lerut
President of the local organising committee ESOT 2015, Brussels
HQ/MULTI/13/0003a
John Forsythe
President-elect of ESOT
We will say Organ Transplantation
changed medicine. Be part of it.’
Sources panel 1900-1960
1902 – Blood groups A, B, O, AB discovered
K., Landsteiner. Zur Kenntnis der antifermentativen, lytischen und agglutinierenden Wirkungen
des Blutserums und der Lymphe, Zentralblatt Bakteriologie 1900 (27).
1912 – Skin grafting
G., Schöne. Die heteroplastische und homooplastische Transplantation. Berlin : Springer, 1912.
1920s – Discovering the role of the lymphocyte
J.B., Murphy. Factors of resistance to heteroplastic tissue graftings. J Exp Med. 19: 513-522, 1914.
1920s – Discovering the role of the lymphocyte
A.M., Silverstein. The lymphocyte in immunology: from James B. Murphy to James L. Gowans. Nat Immunol. 2001 Jul;2(7):569-71.
1930s – Defining time-lapse
L., Loeb. The biological basis of individuality. s.l. : Thomas, Springfield, IL, 1945.
1936 – First human-to-human kidney transplant
E., Matevossian. Surgeon Yurii Voronoy (1895-1961) - a pioneer in the history of clinical
transplantation: in memoriam at the 75th anniversary of the first human kidney transplantation.
Transplantation International. 2009; 22(12):1132-9.
1940s – Medawar’s ground-breaking work in immunology
C.F., Barker. Cold Spring Harb Perspect Med 2013;3:a014977.
1950 – Blood cell types
R.D., Owen. Immunogenetic consequences of vascular anastomoses between bovine twins. Science .
102: 400-407, 1945.
1954 – First successful kidney transplantation
P., Morris. “Joseph E. Murray (1919–2012)”. Nature 493 (164). 2013.
1940s – Medawar’s ground-breaking work in immunology
Nobel Lectures, Physiology or Medicine 1942-1962, Elsevier Publishing Company, Amsterdam, 1964.
HQ/MULTI/13/0003a
Back to panel
Sources panel 1960-1980
1967 – First successful human heart transplant
C., Barnard. The operation: A human cardiac transplant. S Afr Med J. 41:1271, 1967.
1970s – Researchers discover new compound for transplant drug
J.F., Borel. History of the discovery of cylosporin and its early pharmacological development. Wien
Klin Wochenschr. 2002 Jun 28;114(12):433-7.
HQ/MULTI/13/0003a
Back to panel
Sources panel 1980-1990
1987 – New transplant drug discovered
Goto T, Kino T, Hatanaka H, et al. Discovery of FK 506, a novel immunosuppreasant isolated from
Streptomycea tsukubaensis. Transplant Proc 1987;19(Suppl 6):4-8.
1988 – FDA approves organ preservation solution
FO, Belzer. The use of UW solution in clinical transplantation - A four year experience. Ann Surg
215: 579–585. 1992.
1987 – New transplant drug discovered
Kino T., FK 506: a novel immunosuppressantisolated from streptomyces. J Antibiot (Tokyo). 1987;
40:1249.
Starzl T. et al., FK 506: a potential breakthrough in immunosuppression. Transplant Proc. 19 Suppl
3:104, 1987.
Starzl T. et al, Second international workshop on FK 506 - a potential breakthrough in
immunosuppression: clinical implications. Transplant Proc. 22 (Suppl.1):113, 1990.
Prograf, Summary of Product Characteristics.
HQ/MULTI/13/0003a
Back to panel
Sources panel 1990-2000
1991 – The first Banff Classification meeting
Solez K. et al., Kidney Int. 1993 Aug;44(2):411-22.
1994 – FDA approves Tacrolimus (Prograf® Astellas)
Prograf, Summary of Product Characteristics.
KDIGO guideline for kidney transplant recipients. Am J Transplant. 2009 Nov;9 Suppl 3:S1-155.
1995 – FDA approves Mycophenolate mofetil (MMF, CellCept® Roche)
First Approval For Roche’s Mycophenolate Mofetil. The Pharma letter 15 May 1995.
Ratner LE, Ciseck LJ, Moore RG, Cigarroa FG, Kaufman HS, Kavoussi LR. Laparoscopic live donor
nephrectomy. Transplantation1995; 60: 1047–1049.
1997 – Successful knee-transplantation
Hofmann GO. et al., Vascularized knee joint transplantation in man: a report on the first cases.
Transpl Int. 1998;11 Suppl 1:S487-90.
1998 – First successful hand transplantation
Dubernard JM, Owen E, Herzberg G, et al. Human hand allograft: report on first 6 months. Lancet.
1999;353(9161):1315-20.
1991 – The first Banff Classification meeting
Solez K et al.; The Banff classification revisited; Kidney International (2013) 83:201-206.
Billingham ME, Cary NR, Hammond ME et al. A working formulation for the standardization of nomenclature in the diagnosis of heart and lung rejection: Heart Rejection Study Group. The International Society for Heart Transplantation. J Heart Transplant 1990.
Solez K et al. International standardization of criteria for the histologic diagnosis of renal allograft rejection: the Banff working classification of kidney transplant pathology. Kidney Int.
1993 Aug;44(2):411-22.
HQ/MULTI/13/0003a
Back to panel
Sources panel 2000-2010
2006 – First successful human penis transplant
Hu W. et al.,. A preliminary report of penile transplantation: part 2; Eur Urol. 2006 Nov;50(5):
1115-6.
2007 – Ekberg et al publish the ELITE-Symphony study
Ekberg H et al., Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med.
2007 Dec 20;357(25):2562-75.
2008 – First successful complete full double arm transplant
Transplantationsmedizin: Erstmals komplette Arme verpflanzt. Dtsch Arztebl 2008; 105(33).
2008 – First transplant of a human windpipe using a patient’s own stem cells
Macchiarini P etal.,Clinical transplantation of a tissue-engineered airway;. Lancet 2008; 372:
2023–30.
2008 – First successful transplantation of near total area of face
Siemionow M. etal., Near-total human face transplantation for a severely disfigured patient in the
USA. Lancet. 2009 Jul 18;374(9685):203-9.
2008 – First successful complete full double arm transplant
World`s first double arm transplant as man gets teenager`s limbs in 16-hour operation. Mail
Online, 2 August 2008.
HQ/MULTI/13/0003a
Back to panel
Sources panel 2010-2011
2011 – Tacni® is launched in countries in Europe (referring to the statement gold standard regimen)
KDIGO guideline on kidney transplantation: Am J Transplant. 2009 Nov;9 Suppl 3:S1-155
2011 – First double leg transplant
Cavadas P et al., American Journal of Transplantation 2013; 13: 1343–1349;
http://www.bbc.co.uk/news/health-22855670
HQ/MULTI/13/0003a
Back to panel
Sources panel 2012-2013
2013 – Discarded kidneys can be used to generate new kidneys
Orlando G. et al.; Discarded human kidneys as a source of ECM scaffold for kidney regeneration
technologies. Biomaterials. 2013 Aug;34(24):5915-25.
HQ/MULTI/13/0003a
Back to panel