The Nonlinear Library LW - The likely first longevity drug is based on sketchy science. This is bad for science and bad for longevity. by BobBurgers
Dec 12, 2023
08:26
Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: The likely first longevity drug is based on sketchy science. This is bad for science and bad for longevity., published by BobBurgers on December 12, 2023 on LessWrong.
If you are interested in the longevity scene, like I am, you probably have seen press releases about the dog longevity company, Loyal for Dogs, getting a nod for efficacy from the FDA. These have come in the form of the New York Post calling the drug "
groundbreaking", Science Alert calling the drug "
radical", and the more sedate New York Times just asking, "Could Longevity Drugs for Dogs Extend Your Pet's Life?", presumably unaware of Betteridge's Law of Headlines. You may have also seen the coordinated Twitter offensive of people
losing their shit about this, including their lead investor, Laura Deming, saying that she "
broke down crying when she got the call".
And if you have been following Loyal for Dogs for a while, like I have, you are probably puzzled by this news. Loyal for Dogs has been around since 2021. Unlike any other drug company or longevity company, they have released almost zero information (including zero publications) about their strategy for longevity.
These thoughts swirling around my head, I waded through the press releases trumpeting the end of dog death as we know it in order to figure out what exactly Loyal is doing for dog longevity. And, what I found first surprised me, then saddened me. Loyal did not prove efficacy in dog longevity. They found a path around the FDA instead. That's the surprising part. The sad part is that, in doing so, they relied on some really sketchy science.
And I think that, based on their trajectory, they won't just be the first company to get a drug approved for longevity. They will be the first one to get a longevity drug pulled for non-efficacy as well, and put the field back years.
So let's start with how they got their drug approved in the first place. Well, they didn't. To get drugs approved in animals, you need to prove three things: efficacy, safety, and manufacturing consistency. Normally, efficacy is the hardest part of this, because you have to prove to the FDA that your drug cures the disease that it's supposed to. This is especially hard in aging, because any aging trial would take a long time. Loyal found a way around that.
If you can instead prove to the FDA that it would be too difficult to test your animal drug for efficacy before releasing it, they allow you to sell the drug first, and prove the efficacy later. This is a standard called "reasonable expectation of effectiveness".
So, what exactly did Loyal show to the FDA to prove that there was a reasonable expectation their drug would be effective in aging? Well, it's hard to tell, because, again, Loyal has released very little data. But, based on the NYT article and
their blog post, I can sketch out a basic idea of what they did.
Loyal's longevity drug is an injectable insulin-like growth factor 1, or IGF-1, inhibitor. As the name suggests, IGF-1 is closely related to insulin and is regulated by insulin. Also as the name suggests, IGF-1 causes things to grow. High IGF-1 causes acromegaly, the condition that makes people look like storybook giants.
Loyal gave their IGF-1 inhibitor to healthy laboratory dogs (and possibly diabetic dogs, although it's hard to tell). Lo and behold, it lowered IGF-1. It probably also reduced insulin. They then looked at healthy pet dogs, and found that big dogs had higher levels of IGF-1, which is one of the reasons they're big. Small dogs had lower levels of IGF-1. Small dogs, as we all know, live longer than big dogs. Therefore, Loyal said, our IGF-1 inhibitor will extend the life of dogs.
Needless to say, this is bad science. Really bad science. There are holes big enough in this to walk a Great Dane through, which I'll talk about in a sec. Apparent...
If you are interested in the longevity scene, like I am, you probably have seen press releases about the dog longevity company, Loyal for Dogs, getting a nod for efficacy from the FDA. These have come in the form of the New York Post calling the drug "
groundbreaking", Science Alert calling the drug "
radical", and the more sedate New York Times just asking, "Could Longevity Drugs for Dogs Extend Your Pet's Life?", presumably unaware of Betteridge's Law of Headlines. You may have also seen the coordinated Twitter offensive of people
losing their shit about this, including their lead investor, Laura Deming, saying that she "
broke down crying when she got the call".
And if you have been following Loyal for Dogs for a while, like I have, you are probably puzzled by this news. Loyal for Dogs has been around since 2021. Unlike any other drug company or longevity company, they have released almost zero information (including zero publications) about their strategy for longevity.
These thoughts swirling around my head, I waded through the press releases trumpeting the end of dog death as we know it in order to figure out what exactly Loyal is doing for dog longevity. And, what I found first surprised me, then saddened me. Loyal did not prove efficacy in dog longevity. They found a path around the FDA instead. That's the surprising part. The sad part is that, in doing so, they relied on some really sketchy science.
And I think that, based on their trajectory, they won't just be the first company to get a drug approved for longevity. They will be the first one to get a longevity drug pulled for non-efficacy as well, and put the field back years.
So let's start with how they got their drug approved in the first place. Well, they didn't. To get drugs approved in animals, you need to prove three things: efficacy, safety, and manufacturing consistency. Normally, efficacy is the hardest part of this, because you have to prove to the FDA that your drug cures the disease that it's supposed to. This is especially hard in aging, because any aging trial would take a long time. Loyal found a way around that.
If you can instead prove to the FDA that it would be too difficult to test your animal drug for efficacy before releasing it, they allow you to sell the drug first, and prove the efficacy later. This is a standard called "reasonable expectation of effectiveness".
So, what exactly did Loyal show to the FDA to prove that there was a reasonable expectation their drug would be effective in aging? Well, it's hard to tell, because, again, Loyal has released very little data. But, based on the NYT article and
their blog post, I can sketch out a basic idea of what they did.
Loyal's longevity drug is an injectable insulin-like growth factor 1, or IGF-1, inhibitor. As the name suggests, IGF-1 is closely related to insulin and is regulated by insulin. Also as the name suggests, IGF-1 causes things to grow. High IGF-1 causes acromegaly, the condition that makes people look like storybook giants.
Loyal gave their IGF-1 inhibitor to healthy laboratory dogs (and possibly diabetic dogs, although it's hard to tell). Lo and behold, it lowered IGF-1. It probably also reduced insulin. They then looked at healthy pet dogs, and found that big dogs had higher levels of IGF-1, which is one of the reasons they're big. Small dogs had lower levels of IGF-1. Small dogs, as we all know, live longer than big dogs. Therefore, Loyal said, our IGF-1 inhibitor will extend the life of dogs.
Needless to say, this is bad science. Really bad science. There are holes big enough in this to walk a Great Dane through, which I'll talk about in a sec. Apparent...