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Entyce Capromorelin Appetite Stimulant

A Possible Option For Dogs That Won't Eat

   

 

Ron Hines DVM PhD

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Ghrelin, the complex molecule above and to the right, is a hormone that stimulates appetite in you and your pet. The body naturally produces it, mainly in the walls of the stomach and upper intestine. (ref) Ghrelin triggers a lot of other important activities as well. One is the release of growth hormone (GH) ; in that capacity ghrelin is called a secretagogue. Entyce is one of those secretagogues too - an artificial compound that mimics the effects of ghrelin. Both also increases intestinal motility. That increases the rate at which food passes through your pet's intestine. They inhibit nausea. (ref)   They have the potential to elevates blood glucose through their effects on the liver. Ghrelin also has has positive effects on heart function and blood pressure, increasing the strength of the heart and decreasing blood pressure . (ref1, ref2, ref3) Ghrelin also interplays with various cells of the immune system to enhance their function. (ref) In humans, ghrelin even has positive effects on sleep, anxiety and memory. (ref) If Entyce/ capromorelin has that ability too remains unknown.

Through its effect of stimulating the production of growth hormone, ghrelin (and similar bio-engineered drugs like capromorelin/Entyce) was thought to have the potential to slow the natural muscle loss and debility that comes with old age. Because of that, ghrelin it was a prime candidate for pharmaceutical companies looking for ways to slow the adversities of human aging.

The first problem they had was that ghrelin is a large molecule – too large to be absorbed intact through the intestine - so it could not be given orally. Pfizer got to work on that in the early 2000s. They engineered more powerful molecules (agonists) with similar effects to ghrelin (= artificial secretagogues).  These were smaller molecules so they could be given orally. (ref1, ref2)

One of them was capromorelin (aka CP-424391-18 aka AT-002), It is the molecule above and  to the left at the beginning of this page.

Although initial studies on the use of capromorelin were promising (ref) , Pfizer halted the drug’s clinical trials in 2006. Although the reasons for halting the studies were not clearly announced, rumor had it that fat gain (rather than lean muscle gain) and side effects were among the reasons. (ref) Although no countries have yet approved the drug for general use in humans (as of 7/16) , from time to time, positive results on capromorelin are still published. (ref1, ref2)

It is very difficult to get a drug approved in America to combat normal human aging. That is because our FDA does not consider normal aging to be a disease. So the FDA sets the bar extremely high for approval of such products. (ref) There are occasionally documented drops in growth hormone levels that are excessive for a person's natural age (GHD). Perhaps capromorelin will eventually be approved to treat those cases. (ref)

So I do not believe that Pfizer is actively pursuing the licensure of capromorelin in humans at this time. Although some initial Pfizer studies were done in laboratory dogs, Pfizer’s split-off veterinary branch Zoetis  apparently did not want capromorelin either. However, a small player in the current veterinary pharmaceutical market, Aratana Therapeutics, saw a potential market for capromorelin. (ref)  They  applied for and received an FDA license to market capromorelin for short term (a maximum of 4 days) use as an appetite stimulant in dogs. That application was approved in May of 2016. It is my understanding that the company plans to make the drug available to a “select” group of veterinary specialists on or about February of 2017.

Many of the common disease that dogs develop lead to poor appetite and weight loss. Aratana gives that number at 10 million dogs per year. Some of those diseases cause an inevitable downward spiral regardless of the pet’s willingness to eat. But some pets, no doubt, would live longer, and perhaps even recover if they could be induced to eat. For those dogs, Entyce might be helpful. The FDA has only approved the use of this drug in dogs for four days. But veterinarians have very wide latitude in how they prescribe drugs and some will certainly suggest it be given longer when Entyce appears to be enhancing the pet’s health and well-being. 

Entyce/capromorelin also increases the body’s production of growth hormone (GH aka somatotropin) and IGF-1. Both are anabolic agents. That is, they favor the building up of muscle, overall vitality and positive mood. But, over time, anabolic agents can also have negative effects on blood pressure, blood sugar level, the liver and the heart.

So far, there is very little in the scientific literature that allows a veterinarian to estimate the effectiveness of this drug in dogs. There are so many reasons a pet might not want to eat and this drug does not address those many potential causes of inappetence (poor appetite). When it is effective, it is thought to be working through appetite centers in the brain - not the underlying health issues responsible for a lack of appetite. But with its multiple targets throughout the body, that is not entirely certain. So this medication is likely to help some dogs but not others. Its effects are rapid (a matter of hours), so it should not take long to see if it is beneficial to a specific pet.

In clinical trials in dogs, side effects were said to be minimal. They included diarrhea, vomiting, increased thirst and drooling (hypersalivation). In a news release, the Company said it plans to begin supplying Entyce to “a small group of veterinary specialists” beginning in 2017. In that release, they said that 68% of the dogs given Entyce were reported by their owners to be eating better, versus 44% of the owners who receive a similar looking liquid that did not contain the drug (a placebo) that also though their dog's appetite improved. (ref) That is encouraging - but only a first step. (ref)

In the precautionary statement, available in July 2016, proposed to accompany the drug, it is suggested that Entyce be used cautiously in dogs with liver or kidney problems or pets receiving other medications that might adversely affect their liver. When the drug was given to beagles daily at the recommended dose for one year, increased salivation, reddened/swollen paws, increased liver size and changes in liver cells were noted in some of the dogs. Higher daily dosed were associated with increased blood cholesterol, AP and HDLs .  You can read the directions that will come with Entyce here.

There could be a number of situations in which Entyce could be helpful. Dogs recover from complex surgery faster when they consume adequate protein. Entyce might be helpful in those cases. Dogs undergoing chemotherapy sometimes loose their interest in food. Perhaps the drug might help avoid that.

There will probably be off-label uses for Entyce as well. Even before this medicine is available (Feb 2017?) , veterinarians have begun to discussing what those other uses might be. (ref) Older dogs in mental decline might benefit. (rptref)  Dogs with intestinal stasis (ileus) might also benefit. (ref) ; as might dogs with extensive skin burns, trauma or skin disease. The drug might improve the daily lives of dogs with untreatable cancers (ref) or pets with chronic constipation and megacolon. (ref)

In all those cases, it might be wise to closely monitor the pets liver and kidney function until veterinarians understand the long term effects of these drugs better.

Since capromorelin’s effects are similar in humans, rats and dogs, I see no reason, as yet, why this drug might not have applications in cats as well as dogs. In fact, the company stated in one presentation that capromorelin's effects on cats were similar. (ref) Cat process certain medications differently than dogs - particularly those that are modified or eliminated by their livers. So I would be exceedingly cautious in off-label uses until we understand this medication better.

When Entyce does become available, I would be quite interested to receive reports of owner using it in their pets; or from anyone else who has information to add. Based on that, I plan to modify this article accordingly as time goes by. So please do contact me. I am sure there is still a lot we have to learn.