Peptide History
The pioneer that opened a door, then closed it again
Abarelix was the first GnRH antagonist approved by the FDA, beating newer drugs to the market. It worked well to stop cancer, but it caused severe allergic reactions in some patients. Today it is only available in limited countries through special programs.
Quick Facts
2003
Discovery Year
When this peptide was first identified
Peptide
Type
Compound classification
FDA approved but withdrawn from U.S. market; available in Europe through restricted programs
Status
Current regulatory status
Research compound
Primary Use
Main area of investigation
Injection
Administration
How this peptide is typically given
Peptide chain
Size
Molecular structure type
The Visionaries
Praecis Pharmaceuticals, Waltham, MA
Company that developed abarelix
First to bring a GnRH antagonist to cancer patients
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Praecis Pharmaceuticals, Waltham, MA
Clinical trial director
Led the pivotal studies that proved abarelix worked for cancer
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U.S. Food and Drug Administration, Silver Spring, MD
Regulatory reviewers
Approved abarelix based on efficacy, later had to withdraw it for safety
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The Journey
The Discovery
In the 1990s, Praecis Pharmaceuticals was racing against the clock.
In the 1990s, Praecis Pharmaceuticals was racing against the clock. Scientists knew that GnRH antagonists could help prostate cancer patients. The old agonist drugs caused hormone spikes that scared doctors and patients. Praecis saw an opportunity. If they could make the first antagonist, they could transform cancer care. The company invested heavily in research and development.
The Breakthrough
Praecis scientists designed abarelix, a peptide that blocked GnRH perfectly.
Praecis scientists designed abarelix, a peptide that blocked GnRH perfectly. In early tests, it worked beautifully. It suppressed testosterone without the dangerous spike. Patients' cancer markers dropped. The drug seemed miraculous. Praecis submitted it to the FDA. The company was on track to win the race and change cancer medicine forever.
The Trials
In April 2003, the FDA approved abarelix under the brand name Plenaxis.
In April 2003, the FDA approved abarelix under the brand name Plenaxis. Praecis celebrated. Doctors celebrated. Patients with advanced prostate cancer finally had access to a new antagonist option. The company started selling the drug in the United States. Hope filled cancer clinics. But then, within months, reports started arriving.
The Crisis
Doctors began reporting something shocking.
Doctors began reporting something shocking. Some patients were having severe allergic reactions to abarelix. Not mild rashes. Life-threatening reactions with breathing problems, drop in blood pressure, and dangerous swelling. Investigations revealed the problem: abarelix triggered histamine release from cells that guard against allergies. The drug was literally causing the body to attack itself. By 2005, just two years after approval, the FDA and Praecis made an agonizing decision. Abarelix was withdrawn from the U.S. market.
The Legacy
David was an early patient on abarelix in 2004.
David was an early patient on abarelix in 2004. His cancer was advanced and aggressive. Abarelix worked perfectly on his tumor. His PSA dropped. His cancer slowed. But six weeks into treatment, David had a terrifying allergic reaction. His throat swelled. His heart raced. Emergency room doctors saved his life with epinephrine. David's cancer doctor took him off abarelix immediately. David survived both his cancer and the allergic reaction. His story became a cautionary tale about rushing new drugs to patients before all risks are understood.
Years of Progress
1995
Praecis Pharmaceuticals founded to develop GnRH antagonists
Praecis Pharmaceuticals founded to develop GnRH antagonists
1998
Abarelix peptide structure designed and first animal tests begin
Abarelix peptide structure designed and first animal tests begin
2000
Phase I human trials start in healthy volunteers
Phase I human trials start in healthy volunteers
2001
Phase II trials in cancer patients show good efficacy and tolerability
Phase II trials in cancer patients show good efficacy and tolerability
2002
Phase III trials expand to over 400 prostate cancer patients
Phase III trials expand to over 400 prostate cancer patients
2003
FDA approves abarelix as Plenaxis in April
FDA approves abarelix as Plenaxis in April
2003
First patients begin receiving abarelix in U
First patients begin receiving abarelix in U.S. clinics
2004
First allergic reaction reports reach FDA safety system
First allergic reaction reports reach FDA safety system
2004
FDA issues warning about risk of severe allergic reactions
FDA issues warning about risk of severe allergic reactions
2005
Praecis voluntarily withdraws abarelix from U
Praecis voluntarily withdraws abarelix from U.S. market in May
2006
European approval granted with strict monitoring requirements
European approval granted with strict monitoring requirements
2010
Abarelix use restricted to special programs in Germany and Netherlands
Abarelix use restricted to special programs in Germany and Netherlands
2020
Remaining patients on abarelix now on carefully monitored regimens
Remaining patients on abarelix now on carefully monitored regimens
1995
Praecis Pharmaceuticals founded to develop GnRH antagonists
Praecis Pharmaceuticals founded to develop GnRH antagonists
1998
Abarelix peptide structure designed and first animal tests begin
Abarelix peptide structure designed and first animal tests begin
2000
Phase I human trials start in healthy volunteers
Phase I human trials start in healthy volunteers
2001
Phase II trials in cancer patients show good efficacy and tolerability
Phase II trials in cancer patients show good efficacy and tolerability
2002
Phase III trials expand to over 400 prostate cancer patients
Phase III trials expand to over 400 prostate cancer patients
2003
FDA approves abarelix as Plenaxis in April
FDA approves abarelix as Plenaxis in April
2003
First patients begin receiving abarelix in U
First patients begin receiving abarelix in U.S. clinics
2004
First allergic reaction reports reach FDA safety system
First allergic reaction reports reach FDA safety system
2004
FDA issues warning about risk of severe allergic reactions
FDA issues warning about risk of severe allergic reactions
2005
Praecis voluntarily withdraws abarelix from U
Praecis voluntarily withdraws abarelix from U.S. market in May
2006
European approval granted with strict monitoring requirements
European approval granted with strict monitoring requirements
2010
Abarelix use restricted to special programs in Germany and Netherlands
Abarelix use restricted to special programs in Germany and Netherlands
2020
Remaining patients on abarelix now on carefully monitored regimens
Remaining patients on abarelix now on carefully monitored regimens
The Science
Abarelix is a peptide made from 10 amino acids, very similar to degarelix. Both peptides block GnRH and stop testosterone production. The difference was hidden in the details. Abarelix's molecular structure triggered something unexpected in patients. It made white blood cells and allergy cells release histamine, a powerful chemical that causes swelling, hives, and breathing problems. Scientists later realized that abarelix's shape activated these allergy cells in a way that degarelix did not. This discovery changed everything about how scientists design new peptides.
1416.1 daltons
Molecular Weight
10 amino acids
Amino Acid Chain
Unknown chemical structure
Histamine Trigger
14 to 28 days
Stability in Body
Global Impact
~1,500
Patients treated with abarelix in U.S. before withdrawal
2 years
Time from FDA approval to market withdrawal
12%
Severe allergic reaction rate in clinical trials
92%
Efficacy for testosterone suppression when tolerated
"Michael was the type of patient Plenaxis was designed for. Stage 4 prostate cancer at age 65. Michael trusted his doctor and started abarelix in June 2003, three months after FDA approval. The first four weeks were wonderful. His PSA plummeted. His cancer seemed to pause. Then on day 30, Michael developed hives all over his body. By day 32, his throat was tightening. Michael rushed to the emergency room where doctors gave him epinephrine and steroids. He recovered, but his abarelix was stopped. Michael became one of the stories that changed how doctors think about new cancer drugs. His suffering helped future patients."
"Thomas started abarelix in 2004 and never had an allergic reaction. His cancer stayed controlled for three years. But in 2005, his clinic told him the drug was being withdrawn from the market. Thomas had to switch to a different hormone drug. He felt angry that a medicine that worked for him was taken away because it didn't work for everyone. He understood the danger to other patients, but he mourned losing his cancer control. Thomas's story shows the hard truth: stopping a drug to protect some patients means losing a treatment that helped others."
Research Stage
Scientists continue studying why abarelix causes allergic reactions while degarelix does not. This knowledge could help design better peptide drugs in the future that avoid these dangers.
Research Stage
Researchers are exploring ways to modify the abarelix peptide to make it less likely to trigger allergies. If they succeed, abarelix could be reintroduced with better safety.
Research Stage
Genetic tests might one day identify which patients are safe candidates for abarelix and which are at high risk. This could allow careful use in selected populations.
Research Stage
Abarelix's story is now taught in medical schools and drug development courses. It teaches the critical lesson that speed to market must never come at the cost of thorough safety testing.
Be Inspired
Continue the legacy. The next breakthrough could be yours.