Macimorelin Acetate
(Macrilen®/Ghryvelin®)

Act I: The Dark Problem

The Test That Made Patients Sick

How doctors were forced to hurt patients to diagnose a hormone problem

For decades, doctors had a serious problem. They needed to know if patients had enough growth hormone, but the test was terrible and dangerous. The only way to check was the insulin tolerance test, called the ITT. Here's how it worked: doctors would inject insulin, which is a hormone that lowers blood sugar. The goal was to make the patient's blood sugar drop so low that the brain would panic and release growth hormone. The idea was: stress triggers the hormone.

But this test was brutal. Patients would shake. They would sweat. Their hearts would race. Some patients would have seizures from dangerously low blood sugar. In rare cases, people actually died from this test. Elderly patients could not take it. People with heart disease could not take it. Patients with a history of seizures could not take it. Think about that: the patients who needed the test most were the ones who could not safely have it.

Doctors felt trapped. They knew the test was dangerous. But without it, they could not diagnose growth hormone deficiency, called AGHD for short. Veterans with traumatic brain injuries often developed AGHD after their injuries. These brave soldiers needed help, but the only diagnostic tool available could kill them.

The medical community knew something had to change. They needed a new way to test for growth hormone that did not risk the patient's life. It seemed impossible. How could doctors trick the brain into releasing growth hormone without putting the patient in danger?

Then, in the late 1990s, scientists discovered something amazing about the body: there was a hormone called ghrelin that could tell the brain to make growth hormone. If doctors could find a way to activate ghrelin, they might have a safer test. But could such a thing be invented?

Act II: The French Innovation

Building a Fake Key in Montpellier

How two chemists invented a molecule that mimics nature

In southern France, at the University of Montpellier, two exceptional scientists were asking different questions. Jean-Alain Fehrentz and Jean Martinez worked at the Institut des Biomolécules Max Mousseron. They were experts in peptides — short chains of amino acids that are nature's building blocks. Natural ghrelin is a small protein with only three key amino acids in a row. Fehrentz and Martinez understood something important: they did not need to build the entire ghrelin protein. They just needed to build the key part — the three amino acids that unlock the growth hormone door.

In chemistry, there is an interesting challenge: natural proteins can break down quickly in the stomach. If doctors gave patients natural ghrelin to drink, the stomach acid would destroy it. They needed something different. They needed a synthetic version — a designed molecule that would survive the stomach and still work.

Fehrentz and Martinez designed a modified tripeptide. Instead of using natural amino acids, they used special versions that were reversed or changed slightly. The molecular formula was C26H30N6O3 — a carefully balanced arrangement of 26 carbon atoms, 30 hydrogen atoms, 6 nitrogen atoms, and 3 oxygen atoms. They called it JMV-1843. This fake key was smaller, tougher, and more clever than the real ghrelin.

The genius of their design was this: when a patient drank JMV-1843, it would survive the journey through the stomach. It would travel to the gut. Then it would attach to the ghrelin sensor — the receptor — just like natural ghrelin would. The body would not know the difference. The brain would see the fake signal and respond by releasing growth hormone, exactly as if the real hormone had appeared.

This was not easy work. Fehrentz and his team had to test hundreds of designs. Each change to the molecule had to be calculated and measured. They had to ensure the fake key would fit the lock perfectly. But by the early 2000s, they had created something remarkable: a molecule that could be taken by mouth and would trick the body safely.

Act III: The Clinical Validation

Proof That Simple Works Better

How doctors proved the new test was safer and smarter than the old one

By 2014, a pharmaceutical company called Aeterna Zentaris had licensed the French invention from CNRS (the French National Center for Scientific Research). Now the hard work of clinical testing could begin. A research team led by Jose Garcia, an endocrinologist at a Veterans Affairs hospital, ran the first major validation study. They gave the molecule to patients and measured whether it worked. The results were excellent: the test identified growth hormone deficiency with 82% sensitivity and 92% specificity. That means it caught most people who had the problem and avoided false alarms.

But the real test came in 2018. Garcia led a massive phase three clinical trial published in the Journal of Clinical Endocrinology and Metabolism. This was the pivotal study that would determine whether the FDA would approve the new molecule. The trial compared the new test directly against the dangerous insulin tolerance test in 99 people who might have growth hormone deficiency, plus 25 healthy controls.

The results were stunning. The new test, now called macimorelin, could be completed in 99% of patients. The old test could only be completed in 82% of patients. Why? Because some patients were too sick, too old, or too fragile to survive the dangerous insulin injection. With macimorelin, elderly patients, heart patients, and seizure-prone patients could finally be tested safely.

When doctors compared the two tests directly in the same people, macimorelin performed beautifully. At a growth hormone threshold of 2.8 nanograms per milliliter, macimorelin had 87% sensitivity and 96% specificity. But the most important finding was this: there were no serious side effects from macimorelin. No seizures. No heart problems. No hypoglycemia. Just patients drinking a solution and waiting 45 minutes.

The reproducibility was also remarkable: when scientists retested 33 patients weeks later, 97% of them got the same results. The test was reliable, consistent, and safe. For the first time in medical history, doctors had a simple, oral way to diagnose growth hormone deficiency that did not require making patients dangerously sick. The case was clear: macimorelin should replace the insulin tolerance test.

Act IV: FDA Approval and Victory

A New Standard for Safe Diagnosis

How a simple oral test changed medical practice forever

On December 20, 2017, the FDA approved macimorelin under the brand name Macrilen. It was a historic moment. For the first time ever, the FDA approved an oral diagnostic test for adult growth hormone deficiency. Macrilen was the first and only test of its kind. The European Commission also approved it as Ghryvelin, making it available across Europe as well.

The approval was not just a regulatory victory. It was a revolution in how doctors could care for patients. Suddenly, physicians who treated elderly patients, heart patients, and seizure patients could finally diagnose growth hormone deficiency safely. Veterans with traumatic brain injuries could get tested. Patients with complicated medical histories no longer had to risk their lives for a diagnosis.

The test is remarkably simple. A patient comes to a clinic in the morning. They drink 0.5 milligrams of macimorelin per kilogram of their body weight dissolved in water. For a person weighing 75 kilograms, that would be 37.5 milligrams total — about 1.3 ounces of liquid. Then they wait 45 minutes. During that time, if their pituitary gland is working normally, it will release growth hormone in response to the macimorelin. At exactly 45 minutes, a nurse draws blood and measures the growth hormone level.

Compare this to the old insulin tolerance test: inject insulin, wait for dangerous hypoglycemia, hope the patient does not have a seizure, measure growth hormone. The old test took hours and risked death. The new test takes 45 minutes and has virtually no risk. It is faster, safer, and more reliable.

Within a few years, approximately 60,000 macimorelin tests were being conducted annually across the United States, Canada, and Europe. Thousands of patients who could never have been diagnosed safely now had answers. Doctors could confidently prescribe growth hormone replacement for those who needed it. Veterans could get the care they deserved. Elderly patients could finally get tested.

The story of macimorelin is ultimately a story about human ingenuity and compassion. Scientists in France asked: how can we copy nature but do it better and safer? Doctors in America asked: how can we help our patients without hurting them? The answer was a simple drink that changed the standard of care forever.

Act V: The Future and Expansion

From Adults to Children and Beyond

How one breakthrough diagnostic is opening new possibilities

The success of macimorelin in diagnosing adult growth hormone deficiency raised an important question: could it work for children too? Children can develop growth hormone deficiency from birth, illness, or brain tumors. But diagnosing it safely in children was even harder than in adults. The insulin tolerance test is particularly dangerous in young children, who cannot tell doctors when they feel symptoms.

Aeterna Zentaris, the company that developed macimorelin, decided to launch a new clinical trial specifically for children. This trial is called the DETECT trial (Detection of Growth Hormone Deficiency in Childhood). The study aims to prove that macimorelin works just as well in children as it does in adults. If successful, the FDA would expand approval to childhood-onset growth hormone deficiency. This would mean millions of children worldwide could finally be safely diagnosed.

The DETECT trial completed enrollment in 2024. Researchers are now analyzing the data. If the results are as promising as the adult studies, we could see pediatric approval within the next few years. For parents of children with growth issues, this could mean getting answers without watching their child suffer through dangerous testing.

Beyond pediatric expansion, scientists are exploring other possibilities for macimorelin. Some researchers wonder whether macimorelin could be used as a therapeutic drug — not just a diagnostic test, but an actual treatment. Growth hormone deficiency causes real problems: poor muscle growth, bone weakness, low energy. What if macimorelin could help treat these conditions, not just diagnose them? Early research suggests promise, but more studies are needed.

There is also interest in using macimorelin in specific patient populations. For example, patients recovering from illness or injury often lose muscle mass and bone strength. Could macimorelin help them recover faster? Cancer patients undergoing chemotherapy often develop hormone problems. Could macimorelin help them? These are questions being asked in laboratories around the world.

The journey of macimorelin from a laboratory in southern France to a diagnostic tool used around the globe shows something important: great medical breakthroughs often come not from chance, but from asking the right questions. When scientists asked how to copy nature safely, when doctors asked how to help patients without hurting them, the answer was this simple oral solution. It reminds us that the best medical innovations are not always the most complicated. Sometimes they are the simplest ones.