CP-424,391: The Growth Hormone Pill That Chose Veterinary
Medicine

The Discovery (Late 1990s - 2003)

The Groton Chemists

When Pfizer invented a pill that mimics a hormone

In the late 1990s, chemists at Pfizer's Groton, Connecticut lab had a big challenge. They wanted to create a pill that could increase growth hormone without needles. Growth hormone is a real hormone in your body that builds muscle and bone. But hormones are usually big peptides made of amino acids. Big molecules get destroyed by stomach acid. How could they make a pill?

Philip Carpimo and his team had an idea. Instead of making the hormone itself, they would make something that looked like a hormone's smaller cousin. They studied peptides that told your body to make more growth hormone. Then they did something clever. They replaced parts of the peptide with smaller molecular pieces. It was like swapping out big building blocks for smaller ones that fit the same slot.

They designed a structure called pyrazolinone-piperidine. This tongue-twisting name just means two rings of atoms arranged in a specific way. The rings were small enough to survive stomach acid but shaped perfectly to fit into the ghrelin receptor. Think of it like a tiny key that opens a tiny lock in your cells.

After months of testing different variations, they found the winner. Capromorelin (the code name CP-424,391) was born. In animal tests, it worked perfectly. Even tiny doses made rats produce more growth hormone. When they gave it by mouth, it still worked. The stomach acid didn't destroy it. The Groton team had created something special: an oral growth hormone pill.

In 2003, Carpimo published the discovery paper. The medicinal chemistry world took notice. This was elegant chemistry. This was innovation. Pfizer had a drug candidate that could help millions. But first, they needed to test it in humans.

The Human Promise (2005 - 2009)

The Elderly Patients

When capromorelin showed real hope for aging bodies

By 2005, Pfizer was ready to test capromorelin in humans. They chose a specific group: people over 65 years old who were getting weak. These were people who walked slowly, had poor grip strength, or fell easily. They had all the signs of aging. Doctors hoped capromorelin could help them regain muscle and strength.

Helen White, MD, led the clinical trial at Duke University. The study was called NCT00527046. Nearly 400 elderly men and women joined. Some received capromorelin pills. Others received sugar pills (placebo). Neither the patients nor the doctors knew who got the real drug. This is called a masked trial. It prevents bias.

They tested four different doses. Some people took 10 milligrams three times a week. Others took smaller doses more frequently. The team measured blood levels of growth hormone and IGF-1 (a marker that grows when growth hormone increases). After six months, the results were clear: capromorelin worked.

Patients taking capromorelin gained about 1.4 kilograms of lean muscle. The placebo group actually lost muscle. Their bones felt stronger. Their arms could grip harder. Most impressively, when researchers tested their walking speed on a challenging course, capromorelin patients walked 0.9 seconds faster. That might sound small, but for a 75-year-old person, it means the difference between staying independent and needing help.

After one year, the benefits grew. Patients could climb stairs faster. Their endurance improved. The data was beautiful. Growth hormone increased. Muscle increased. Walking improved. This was a win for Pfizer. Elderly patients needed better treatments. This could be it. The future looked bright.

The Turning Point (2008 - 2010)

When Blood Sugar Became The Enemy

Why a promising drug had to be abandoned for humans

But then something concerning emerged from the data. Researchers noticed that capromorelin was increasing blood glucose. Some patients had fasting blood sugar levels that climbed. Their insulin resistance increased. These are the first signs of diabetes developing. For young, healthy people, a little increase in blood glucose might not matter. But these were elderly people already at high risk for diabetes. Some of them already had pre-diabetes.

This was the dilemma. Capromorelin built muscle. It helped people walk and climb better. It genuinely improved quality of life. But it pushed patients toward diabetes. Type 2 diabetes brings its own problems: foot sores, kidney disease, blindness, heart attacks, and stroke. For an elderly person, the drug was trading one problem (weak muscles) for a worse problem (diabetes).

Fpizer's leadership faced a hard choice. The trial had a rule built in. If blood sugar problems became clear, they would stop the trial. That rule was triggered. The clinical trial was terminated early. The company decided the risks were too high. Capromorelin could not continue in elderly humans.

This was a devastating moment for Pfizer. They had invested millions. They had a working drug. The chemistry was elegant. The results were real. But in humans over 65, it was not safe enough. The team had to file away their research. Capromorelin became a failed drug. It sat on the shelf. Years would pass before anyone would think about it again.

Helen White published the results in the Journal of Clinical Endocrinology and Metabolism in 2009. The paper was honest. It showed the good results and the bad ones. The scientific community understood: sometimes a good drug cannot help a particular group of people. Sometimes your body is too fragile to take the risks. That was the case with elderly humans and capromorelin.

The Pivot (2014 - 2016)

Dogs Who Wouldn't Eat

How a human failure became a veterinary triumph

In 2014, a different company spotted capromorelin on the shelf. Aratana Therapeutics licensed the compound from Pfizer. Aratana's scientists thought differently than Pfizer's human doctors. They asked a simple question: if capromorelin makes you hungry and increases growth hormone, what about animals that have lost their appetite?

Older dogs suffer from the same problem as older humans. They lose interest in food. They grow thin and weak. Cancer, kidney disease, and age itself make dogs not want to eat. Vets had almost no treatments. They could place feeding tubes. They could use steroids that sometimes helped. But there was no real appetite-stimulating drug for dogs. Until now.

Aratana tested capromorelin in dogs with appetite loss. The results were dramatic. Dogs started eating again. They gained weight. They had more energy. In 2015, the company filed for FDA approval. The agency moved quickly. In May 2016, the FDA approved Entyce (capromorelin for dogs). It was the first ghrelin receptor drug ever approved for veterinary use.

When Entyce launched in September 2016, veterinarians across the country embraced it. Pet owners watched their aging dogs eat again. Dogs with cancer could gain a few more months of quality time with their families. Dogs recovering from surgery ate and healed faster. Entyce became a blockbuster. Thousands of dogs received it every month.

But the success didn't stop there. Aratana looked at cats. Cats with chronic kidney disease face a cruel problem. Their kidneys fail, they feel sick, they stop eating. They lose weight rapidly. They die. Cats are especially picky eaters. Traditional drugs didn't work. In 2017-2018, Aratana tested capromorelin in cats with kidney disease. Again, it worked. Cats ate. Cats gained weight. Cats lived longer. On October 28, 2020, the FDA approved Elura (capromorelin for cats).

Suddenly, a drug that failed to save elderly humans was saving the lives of beloved pets. Dogs and cats with terminal illnesses could enjoy their final months. The irony was beautiful. The same molecule that Carpimo designed at Groton to help aging people ended up helping aging animals. Capromorelin didn't fail. It just needed to find the right patients.

The Legacy (2016 - Present)

A Drug That Found Its Purpose

How failure led to success, and success led to saving lives

Today, capromorelin is a success story. Elanco Animal Health (which acquired Aratana Therapeutics in 2019) now markets both Entyce and Elura. These are among the most important drugs in veterinary medicine. Every day, veterinarians prescribe them to help animals in need. The molecule that Carpimo designed 25 years ago is actively saving lives.

The story of capromorelin teaches an important lesson. Sometimes the best drug is not for the disease it was first designed to treat. Sometimes a breakthrough compound has to wait for the right problem to come along. Pfizer's chemists created something beautiful and useful. The human clinical trial proved it worked. But humans over 65 couldn't take it safely. That wasn't a failure of the chemistry. It was just a mismatch between the drug and the patient.

When veterinary scientists looked at the same molecule, they asked different questions. They weren't trying to treat age-related weakness in people who would live another 20 years. They were trying to help animals facing weeks or months. For a dog with cancer who hasn't eaten in a month, a slightly increased risk of blood sugar problems doesn't matter. The dog needs to eat now. Capromorelin let them eat.

Today, millions of pet owners have experienced the impact of capromorelin. They watched their aging dogs recover appetite and energy. They saw their cats with kidney disease gain weight and live months longer. They felt their pet's warm breath again, their purr return, their interest in life rekindled. All because of a tiny molecule designed by clever chemists at Pfizer decades earlier.

The future may hold new chapters for capromorelin. Research continues on ghrelin receptor agonists for human aging, muscle wasting in cancer patients, and other conditions. Perhaps new versions will be developed that don't raise blood sugar as much. Perhaps capromorelin itself will find other veterinary uses. But already, its greatest achievement is clear: it proved that science's greatest breakthroughs sometimes come not from getting it right the first time, but from finding the right problem to solve.