GENET archive

[Index][Thread]

1-Proteins: European Medicines Agency did not license world's first drug from GE animals



                                 PART I
------------------------------- GENET-news -------------------------------

TITLE:  Europe Rejects Genetically Engineered Drug
SOURCE: The New York Times, USA, by Andrew Pollack
        http://www.nytimes.com/2006/02/24/business/worldbusiness/24drug.html
DATE:   24 Feb 2006

------------------ archive:  http://www.genet-info.org/ ------------------


Europe Rejects Genetically Engineered Drug

European regulators declined yesterday to approve what would have been
the first drug produced in the milk of genetically engineered animals,
dealing a setback to a fledgling industry that aims to convert cows,
goats and rabbits into low-cost pharmaceutical factories.

The decision was closely watched because companies developing drug-
producing animals need an approval from either the United States or
Europe to persuade pharmaceutical companies to try the production method.

The drug's developer, GTC Biotherapeutics, said it would appeal the
decision, adding that the ruling was based mainly on a problem with its
clinical trial, not on the fact that the drug was made in goats.

"With a new technology there is a conservatism that is not
inappropriate," Geoffrey F. Cox, chief executive of GTC, said in a
conference call with analysts. But he added, "There is no way with this
company and what we have achieved over 15 years that we will let this
block us from getting the product to market."

Shares of GTC, which is based in Framingham, Mass., fell 90 cents, or 40
percent, to $1.35.

GTC and a few other companies put human genes into animals so they
produce a human protein in their milk. The animals can be milked and the
protein purified for use as a drug.

The companies say the method is a cheaper and easier way to produce
biotechnology drugs. Many biotech drugs, like cancer-fighting monoclonal
antibodies, are made in vats containing cultures of genetically
engineered animal cells. Such factories can cost several hundred million
dollars.

Other protein drugs, like the one GTC is developing, are extracted from
donated blood, but are found in such minute quantities that they are
often in short supply. GTC said it would take 90,000 blood donations to
obtain as much of the protein as one of its goats can produce in a year.

But drug companies have been reluctant to use the technology, in part
because they were unsure how readily regulators would approve drugs
developed that way. So GTC decided to seek an approval by itself, even
if sales of the drug would be small.

It tested an anticlotting protein called antithrombin on patients who
have a rare inherited deficiency of the protein and are at risk of
potentially fatal blood clots. The company tested the drug on 14 people
who were undergoing surgery or giving birth. At those times, because of
the risk of bleeding, such patients cannot take the blood thinners they
usually use to prevent clots.

The European Medicines Agency said yesterday that its advisory committee
recommended against approval because too few patients undergoing surgery
were tested. Also, the drug tested was not made in exactly the same way
as the drug that would be sold, because a filtration step was added
after the trial began.

GTC executives said the committee decided not to count pregnant women
included in the test, because the dosing of the drug was not optimal.
They also said the regulators had concerns about possible immune
reactions to the drug, though none were seen.

The company is doing another trial aimed at applying early next year for
approval in the United States.

Another company, Pharming, has asked the Food and Drug Administration to
certify its human lactoferrin protein, made in transgenic cows, as
"generally recognized as safe." That designation would allow Pharming to
sell the protein for use in food products. Human lactoferrin is
naturally found in mother's milk.

Pharming, a Dutch company that has recovered from a financial collapse a
few years ago, is also in late-stage clinical trials of a protein called
C1 inhibitor, produced in rabbits, to treat hereditary angioedema.

PharmAthene, based in Annapolis, Md., is trying to win a contract from
the Defense Department to supply a protein, butyrylcholinesterase, to
help treat people exposed to nerve gas. The protein is found in blood
plasma but in such small amounts it would be impossible to make as much
as the military needs, the company said.

"It would take approximately 500 liters of plasma to produce a single
dose," the company's director for education, Stacey Jurchison, said. "We
have about 250 goats. The milk they would produce in a year's time would
be sufficient to produce 100,000 doses."

Production of drugs in transgenic animals is not the only part of
barnyard biotechnology that has suffered setbacks. So has cloning, which
involves making copies of desirable animals, rather than putting foreign
genes in them. The F.D.A. has continually put off making an expected
decision that the meat and milk from cloned animals and their offspring
are safe to consume.


                                 PART II
------------------------------- GENET-news -------------------------------

TITLE:  'Pharmed' goat drug not approved
SOURCE: British Broadcasting Corporation
        http://news.bbc.co.uk/2/hi/science/nature/4746736.stm
DATE:   24 Feb 2006

------------------ archive:  http://www.genet-info.org/ ------------------


'Pharmed' goat drug not approved

An application to license the world's first medicine to be produced from
a GM animal has been turned down.

Atryn is an anti-clotting agent and would have been used by people with
an inherited disease leaving them prone to developing blood clots.

A company had engineered the goats so they produced the drug in their milk.

The European Medicines Agency said the company applying for the licence
had failed to demonstrate the benefits of the drug outweighed its risks.


Milk manufacture

Potential recipients of Atryn number around 1 in 5,000 in the UK.

Sufferers are born missing one copy of the anti-thrombin gene, resulting
in underproduction of this protein in their bodies and leaving them
vulnerable to blood clots.

Normally, patients are maintained on blood thinners such as Warfarin;
but if they are giving birth or undergoing surgery this is deemed too
risky, and they are given replacement anti-thrombin.

The only current source for this is from human blood plasma.

While there have never been any contamination problems with anti-
thrombin products, fears about the possible transmission of diseases,
such as vCJD, as has been seen with whole blood, make doctors unwilling
to expose their patients to plasma products unless they have no choice.

GTC Biotherapeutics, based in the US, genetically modified goats to
contain a human gene that codes for anti-thrombin. The transgenic goats
are then able to produce the protein in their milk.

Market desire

Geoffrey Cox, chief executive of the company, said: "It takes just 18
months to produce a lactating animal and in a single year one goat
produces the equivalent of 90,000 blood collections."

The goat-derived drug was studied in 14 patients with the inherited
disease: five were given Atryn during surgery and nine were given the
drug during childbirth.

But the European Medicines Agency said it was not inclined to give the
drug a licence at this stage because the research had not looked at
enough surgical cases, and the childbirth studies could not be used in
support.

The agency also said that not enough evidence was produced to show if
trial patients were developing an unfavourable immune response to the drug.

In the late 1990s, biotech investors went wild for the promise of
living, breeding drug producers, delivering products at a fraction of
the cost of a traditional biotech factory, but delivery of these
products has been slow to come to market.

This latest decision marks a further setback in moving these transgenic
drugs from bench to bedside.


                                 PART III
------------------------------- GENET-news -------------------------------

TITLE:
SOURCE: European Medicines Agency, UK, Atryn Q&A, Doc.Ref. EMEA/62022/2006
        http://www.emea.eu.int/pdfs/human/opinion/QandA_Atryn_6202206en.pdf
DATE:   23 Feb 2006

------------------ archive:  http://www.genet-info.org/ ------------------


QUESTIONS AND ANSWERS ON RECOMMENDATION FOR REFUSAL OF MARKETING
APPLICATION for ATRYN

International Non-proprietary Name (INN): antithrombin alfa

On 22 February 2006, the Committee for Medicinal Products for Human Use
(CHMP) adopted a negative opinion, refusing the marketing authorisation
for ATryn 1750 IU powder for solution for infusion, to be used in
surgical patients with congenital antithrombin deficiency for the
prophylaxis of deep vein thrombosis and thromboembolism in clinical risk
situations, i.e., during the peri-surgical period. The company who
applied is Genzyme Europe B.V. They may request a re-examination of the
opinion within 15 days of its receipt.

What is ATryn?

ATryn is a white powder to be made up into a solution for infusion (drip
into a vein). ATryn contains the active substance antithrombin alfa.

What was ATryn expected to be used for?

ATryn was to be used in patients who have an inherited reduction of the
protein antithrombin, to prevent problems due to the formation of clots
in the vessels of the legs (deep vein thrombosis, DVT) or in other
vessels of the body (thromboembolism) during high risk situations (for
example major surgery).

How is ATryn expected to work?

ATryn is an anti-clotting agent. The active substance in ATryn,
antithrombin alfa, is a copy of the natural blood protein that is
produced by recombinant DNA technology. It is extracted from the milk of
goats who have a gene (DNA) inserted, which make them able to produce
the human protein in their milk.

In the body, antithrombin blocks thrombin, one of the substances
involved in blood coagulation (clotting). Thrombin plays a central role
in the process of blood clotting. Patients who have a congenital
antithrombin deficiency have blood levels of antithrombin that are lower
than normal, which may result in a reduced anti-clotting capacity of the
blood. This increases the risk of the formation of clots during high-
risk situations. ATryn would be expected to correct the antithrombin
deficiency and to give temporary control of the clotting disorder.

What documentation has been presented by the Company to support the
application to the CHMP?

The effects of ATryn were first tested in experimental models before
being studied in humans. ATryn was studied in 14 patients with
congenital antithrombin deficiency at risk of a thromboembolic event
(surgery [5 patients] or childbirth [9 patients]). The Company also
presented the results of the treatment in 5 patients who received the
medicine during surgery in a 'compassionate use programme' (when a
Company makes available to doctors a medicine before it is fully
licensed to treat a specific patient who needs it).

Which were the major concerns, which lead to the refusal of the
marketing authorisation by the CHMP?

The disease is rare (it is estimated that about one person in 3, 000 to
5,000 have a congenital antithrombin deficiency), and this explains why
few patients have been treated during the studies.

However, for the proposed indication, only 5 surgical cases were
considered. The CHMP considered this number to be too small, and not in
line with the EMEA's recommendations (scientific advice) to the Company
of 12 patients. The results in patients treated in the compassionate use
programme and at childbirth could not be used to support the proposed
use in patients undergoing surgery. Also the process for the production
of the medicine used in the studies is not exactly the same as that
which would have been marketed (addition of a filtration step).

ATryn is a protein-based medicine, and, like all protein-based
medicines, it is possible that patients develop antibodies (proteins
produced in response to ATryn). The CHMP considered that the Company did
not carry out enough studies looking for the development of antibodies.

At this point in time, the CHMP was of the opinion that it was not yet
demonstrated that ATryn's benefits are greater than its risks. Hence,
the CHMP recommended that ATryn be refused marketing authorisation.

What are the consequences of the refusal for patients undergoing
clinical trials/compassionate use programmes with ATryn?

No consequences for patients undergoing clinical trials have been
identified by the CHMP. If you are in a clinical trial or compassionate
use programme with ATryn and need more information about your treatment,
contact the doctor who is giving it to you.


                                 PART IV
------------------------------- GENET-news -------------------------------

TITLE:  GTC BIOTHERAPEUTICS EXPECTS CHMP TO ISSUE NEGATIVE OPINION ON ATryn(R)
SOURCE: GTC Biotherapeutics, USA
        http://www.transgenics.com/news.html
DATE:   23 Feb 2006

------------------ archive:  http://www.genet-info.org/ ------------------


GTC BIOTHERAPEUTICS EXPECTS CHMP TO ISSUE NEGATIVE OPINION ON ATryn(R)

FRAMINGHAM, MA - February 23, 2006 -- GTC Biotherapeutics, Inc. ("GTC",
Nasdaq: GTCB) announced today that it has been told that the Committee
for Medicinal Products for Human Use (CHMP) of the European Medicines
Agency (EMEA) intends to issue a negative opinion on the market
authorization application (MAA) for ATryn(R), GTC's recombinant form of
human antithrombin. On the basis of recent conversations, GTC
understands that the CHMP, after excluding data from pregnant patients,
determined that an insufficient number of surgical patients were
enrolled to support approval. In addition, GTC understands that the CHMP
has concerns about sufficient immunologic data and the lack of clinical
data from ATryn(R) produced with an additional filtration step. GTC
intends to take advantage of the appeal process to request a CHMP re-
examination of GTC's submission.

GTC's European development and commercialization partner, LEO Pharma A/
S, has affirmed that they remain committed to their collaboration with
GTC and will continue to pursue the primary goal of development of an
acquired deficiency indication for Europe. Acquired deficiency
indications represent the most significant market opportunity for the
product. GTC and LEO entered into a collaborative development and
commercialization agreement for ATryn(R) in Europe, Canada, and the
Middle East in November 2005. GTC is also continuing a multinational
study of ATryn(R) in hereditary antithrombin deficient patients in
preparation for submission of a Biologics License Application (BLA) in
the U.S. Enrollment is planned to be completed in 2006 and a BLA
submitted in the first half of 2007.

"Although we are very disappointed with the late-breaking concerns on
the clinical data and the negative opinion, we are pleased by the
commitment of LEO Pharma to continue working on further development of
this important product in Europe in acquired antithrombin deficiency"
stated Geoffrey F. Cox, Ph.D., GTC's Chairman of the Board and Chief
Executive Officer. "In addition we remain committed to completing our
submission for BLA approval in the US. The US remains a major long term
opportunity for ATryn(R) in a range of hereditary and acquired
deficiency indications. It is also important for our transgenic
technology platform that the CHMP has not identified to us any
significant outstanding issues related to the manufacturing and
production control systems for ATryn(R)."

Antithrombin is a protein in human plasma that has anticoagulant and
anti-inflammatory properties. Patients that have a hereditary deficiency
indication are prone to developing blood clots during high-risk
procedures, such as surgery and childbirth. Providing supplemental
antithrombin during these procedures may prevent the occurrence of DVT's
and other thromboembolic events. Antithrombin supplementation therapy
may also be useful in the treatment of patients who acquire temporary
antithrombin deficiency during certain clinical situations such as
burns, coronary artery bypass surgery, disseminated intravascular
coagulation, sepsis, and bone marrow transplant.


Conference Call Information
GTC will discuss this opinion and the status of ATryn(R) in a web cast
conference call at 9:00 a.m. (Eastern) today. The web cast may be heard
through GTC's web site at www.gtc-bio.com. The dial-in number from
inside the United States is 1-800-901-5231. The dial-in number from
outside the United States is 1-617-786-2961. The participant passcode is
41916712.


About GTC Biotherapeutics, Inc.
GTC Biotherapeutics is a leader in the development, production, and
commercialization of therapeutic proteins through transgenic animal
technology. In addition to the ATryn(R) program, GTC is developing
recombinant human alpha-1 antitrypsin, recombinant human albumin, a
CD137 antibody as a potential treatment for solid tumors, and a malaria
vaccine. In its external programs, GTC's technology is used to develop
transgenic production of its partners' proprietary products, including
both large-volume protein therapeutics as well as products that are
difficult to produce in significant quantities from conventional
recombinant production systems. One of the external programs is in
clinical trials with a transgenically produced product. Additional
information is available on the GTC web site, http://www.gtc-bio.com.


This press release contains forward-looking statements as defined in the
Private Securities Litigation Reform Act of 1995, including without
limitation statements regarding its expectations for the final CHMP
opinion, the development of an acquired deficiency indication with LEO,
the ongoing phase III study and preparation of a BLA, and GTC's request
for a CHMP re-examination of the submission. Such forward-looking
statements are subject to a number of risks, uncertainties and other
factors that could cause actual results to differ materially from future
results expressed or implied by such statements. Factors that may cause
such differences include, but are not limited to, the risks and
uncertainties discussed in GTC's most recent Annual Report on Form 10-K
and its other periodic reports as filed with the Securities and Exchange
Commission, including the uncertainties associated with regulatory
approval and the actions of partners. GTC cautions investors not to
place undue reliance on the forward-looking statements contained in this
release. These statements speak only as of the date of this document,
and GTC undertakes no obligation to update or revise the statements,
except as may be required by law.


CONTACT: GTC Biotherapeutics, Inc.
Thomas E. Newberry Vice President, Corporate Communications (508) 370-5374
Feinstein Kean Healthcare Francesca DeVellis (investors) (617) 577-8110


                                 PART V
------------------------------- GENET-news -------------------------------

TITLE:  'Pharmed' goats seek drug licence
SOURCE: British Broadcasting Corporation, by Rachael Buchanan
        http://news.bbc.co.uk/2/hi/science/nature/4740230.stm
DATE:   22 Feb 2006

------------------ archive:  http://www.genet-info.org/ ------------------


'Pharmed' goats seek drug licence

Imagine you could get life-saving medicines from milking a common
farmyard animal.

That idea moves a step closer to becoming a reality this week, as the
European Medicines Agency (EMEA) considers the final stages of an
application to license a natural human protein extracted from the milk
of goats.

If the EMEA says "yes" on Thursday, Atryn will become the world's first
medicine to be produced from a genetically modified animal and
represents the vanguard of this long-promised science.

The 57 unique goats that produced the drug-laden milk reside on an
anonymous-looking farm belonging to GTC Biotherapeutics, an hour's drive
from Boston, Massachusetts.

To the eye, they are indistinguishable from their fellow ruminants,
jostling in their pens for a better look at their visitors. But what
marks them out is an extra snippet of DNA entwined in their genome.


High yield

It is a human gene that codes for anti-thrombin (AT), an anticoagulant -
a substance that inhibits blood clots from forming. It is usually
extracted from blood plasma.

A decade and a half ago, the company's scientists copied the human AT
gene and attached it to a chunk of goat DNA, the promoter for beta
casein. This gives the instruction to express that gene only in milk and
no where else in the body.

This genetic composite was then injected into a newly fertilised goat
egg and as the sperm and egg fused together, the extra gene was
incorporated into the goat genome.

The embryo was then implanted into a surrogate mother and six months
later the herd founder was born.

For GTC's British born CEO, Geoffrey Cox, goats are an obvious choice of
bioreactor.

"It takes just 18 months to produce a lactating animal and in a single
year one goat produces the equivalent of 90,000 blood collections," he
told the BBC News website.


Birth confidence

Potential recipients of Atryn number around 1 in 5,000 in the UK.

Sufferers are born missing one copy of the anti-thrombin gene, resulting
in underproduction of this protein and leaving them prone to blood clots.

Normally patients are maintained on blood thinners such as Warfarin but
if they are giving birth or undergoing surgery that is too risky, and
they are given replacement anti-thrombin.


The key alteration takes place in a newly fertilised goat egg
The only current source is human blood plasma. While there have never
been any contamination problems with AT products, fears about the
possible transmission of diseases such as vCJD, as has been seen with
whole blood, make doctors unwilling to expose their patients to plasma
products unless they have no choice.

Hayley Jarvis is one such patient - having AT deficiency meant taking
plasma derived anti-thrombin when she had son Oliver.

In a month's time she will take the drug again when she delivers her
second son.

Hayley says she wouldn't have a problem taking a medicine from a goat.
She knows any risks from plasma are theoretical but "there is always
that niggle at the back of your mind," she says. "It would be good to
have a choice."


Animal history

Her physician, Dr Beverley Hunt of St Thomas' hospital London, is an
expert in thrombosis.

She agrees and would welcome an alternative, but Dr Hunt is not put off
by the animal origin of the drug.

"Yes we do need to think about risk of disease transmission from
animals, but we already use direct animal products such as heparin from
pig tissue and leech extracts for blood thinning, without causing harm
to people".

GTC's Atryn goats are not alone in this novel science. Mixed in with the
company's 1,500 strong herd are goats producing a treatment to shrink
solid tumours.

Down the road in Wisconsin, Dutch firm Pharming keep a herd of cows
expressing human lactoferrin - a protein found in breast milk which has
anti-bacterial qualities.

Three and a half thousand miles away on home turf in the Netherlands,
Pharming are milking rabbits for a treatment for hereditary angioedema,
which leads to swelling in various parts of the body.


Slow development

Life-saving goats, cows, rabbits - it's a long way from the laboratory
mice that were the first living transgenic drug factories in 1987.

Back then, human therapeutic proteins produced in animal milk appeared
to offer great economic potential.


Milking future: Goats offer the possibility of high yields
In the late 1990s, biotech investors went wild for the promise of
living, breeding drug producers, delivering products at a fraction of
the cost of a traditional biotech factory. But progress has been slow.

It is nearly two decades since that pioneering mouse and 14 years since
the birth of GTC's first Atryn goat, and not a single product has made
it to market yet.

As investors lost their patience, companies have faced leaner times and
some have gone to the wall.

Now Atryn stands on the brink of European licensing and Pharming's
Lactoferrin could get FDA approval later this year. Maybe 2006 will be
the year transgenic drug production finally makes the leap from bench to
bedside.


--


GENET
European NGO Network on Genetic Engineering

Hartmut MEYER (Mr)
In den Steinäckern 13
D - 38116 Braunschweig
Germany

P: +49-531-5168746
F: +49-531-5168747
M: +49-162-1054755
E: coordination(*)genet-info.org
W: <http://www.genet-info.org>



-----------------------------
   GENET-news mailing list
-----------------------------