FDA approves first ready-to-use liquid stable Glucagon Gvoke

WRITTEN BY: Beyond Type 1 Editorial Team

Editor’s Note: Xeris Pharmaceuticals is slated to host a conference call today at 12:30 pm ET. Beyond Type 1 will update this breaking news as more information becomes available.

On September 10, the FDA approved the Gvoke HypoPen, an emergency glucagon rescue treatment for severe hypoglycemia. The device from Xeris Pharmaceuticals contains a room temperature, liquid-stable form of glucagon that is auto-injected when pressed against the body, similar to how an EpiPen works to treat severe allergic reactions. GVOKE is formulated for use in patients over the age of two and can be administered by caregivers in emergency situations of hypoglycemia.

Once administered, the glucagon works to rapidly increase blood glucose levels by stimulating the liver to release accumulated glucose into the bloodstream. Also approved was the GVOKE PFS, a pre-filled syringe with the same liquid-stable form of liquid glucagon found in the HypoPen. Both options will be available in two doses: a 0.5 mg/0.1 mL dose for pediatric patients and a 1 mg/0.2 mL dose for adolescents and adults.

“This milestone is a positive step forward for the diabetes community as the first pre-mixed, pre-filled, and pre-measured liquid glucagon to effectively treat severe hypoglycemia in both adults and children with diabetes,” said Paul R. Edick, Chairman and Chief Executive Officer of Xeris Pharmaceuticals. “We are actively preparing to introduce GVOKE in two different administration options to accommodate the community’s preferences starting with our pre-filled syringe in 4-6 weeks and the auto-injector in 2020.”

For decades, a Glucagon emergency kit had been the only FDA-approved way to administer glucagon in cases of severe hypoglycemia. However, injectable glucagon was not previously not liquid-stable at room temperature and therefore required mixing a powder and liquid with a syringe, which can be intimidating and prone to user error in emergency situations.

“Until now, many people may have been hesitant to use conventional glucagon kits because the complex preparation felt confusing and perhaps overwhelming. With GVOKE as a new glucagon option, we gain an easy to use and effective solution to a dangerous and stressful event,” said Jeff Hitchcock, founder and president of Children with Diabetes.

FDA approval came after positive results from Phase 3 clinical trials comparing the use of GVOKE to conventional glucagon rescue kits in situations of severe hypoglycemia in both children and adults. These trials saw a 100% treatment success rate in children, and a 99% success rate in adults.

These new, liquid-stable glucagon kits from Xeris represent the second approval of next-generation glucagon in the past two months. In July, the FDA approved the first non-injectable form of glucagon, BAQSIMI. The rescue device from Eli Lilly is a powder form of glucagon administered into the nose, and comes in a single-use dispenser.

Although the HypoPen and PFS are currently only approved to treat severe hypoglycemia, a liquid-stable form of glucagon opens the door to approval for a wider range of future use cases for the drug. Edick told Beyond Type 1 earlier this year that the company was looking at the potential for their product to treat both exercise-induced hypoglycemia and post-bariatric surgery hypoglycemia.

liquid-stable. Nice! Cost?

It’s great to see this shelf-stable liquid glucagon emerge from the regulatory pipeline. My personal interest will increase when/if this product becomes available for mini-doses selectable by the user at a reasonable price.

My endo mentioned this last week at a technology event he and my CDE set up for their patients. In his opinion he thought all T1’s should have this or the nasal glucagon at their disposal.

But same question as @Dave44 - what’s the cost and is it covered by insurance?

I can’t say anything about the price, but you can micro-dose if you want.

See my reference to it on FUD.

Exciting! Can something like this eventually be used in a pump alongside insulin to treat highs and lows?

My endo told me (last November I think) that several research groups were looking at just this idea. I don’t know if anything promising is coming out of it. I’ll ask when I see him next month. Seems to me FDA approved liquid-stable glucagon would go along way toward making this feasible.

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In fact Xeris is working on that:

Data was presented at American Diabetes Association’s 79th Scientific Sessions (ADA), which included preclinical data of our XeriSol™ pramlintide-insulin co-formulation and regular insulin and lispro insulin, clinical data summarizing combined safety and efficacy of Gvoke, as well as clinical data using Xeris’ RTU glucagon in a dual hormone, closed-loop pump system.

https://www.globenewswire.com/news-release/2019/08/06/1897927/0/en/Xeris-Pharmaceuticals-Announces-Second-Quarter-2019-Financial-Results-and-Highlights.html

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That’s an obvious solution I didn’t see. Thanks for the tip.

Now the economics will come into play. I think I can get about 10 mini-gluc doses out of one kit. Not sure how my insurance coverage will work.

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FYI, if you are wanting to mini-dose, and aren’t interested in the auto-injector, I would definitely get the pre-filled syringe option.

I didn’t understand that the “pre-filled syringe” would permit partial dosing. I sure hope that is the case.

Edited to add:

I just read this DiabetesMine piece with the details for this new glucagon. Here’s confirmation of what I thought might be the single use design:

03%20AM

I am puzzled as to how they’ve built-in a single dose only feature. In any case, it does make possible the technique that @Eddie2 described above.

Regarding the pricing of this new product, I found this from the same DiabetesMine source I cited above.

Xeris isn’t specific on actual list prices, but says only that pricing will be “in parity” with existing glucagon products on the market. If so, that translates to roughly $280 for a single Gvoke injector pen, and ~$561 for a two-pack.

It has GOT to be cheaper to raise one’s bg’s with food. I’m not talking about when it is a dire emergency, but the talk of “mini dosing” is not the same as someone passed out with a bg hovering near zero. In lieu of mini dosing, why not eat something?

That’s a sensible question. Eating something will definitely be cheaper than taking a mini-gluc dose. There are a few reasons why some people would prefer to avoid taking in the extra glucose.

  • It’s extra calories that someone who would like to lose weight might wish to avoid.

  • Using a mini-glucagon shot is closer to a healthy glucose metabolism than is eating to compensate for the hypo.

  • Since glucagon provokes the liver to release glycogen, it uses a pathway that those of us with T1D have essentially lost. I hypothesize that this does no harm and may provide some benefit science is not yet aware of. Perhaps it provides an exercise that benefits the liver’s ability to perform this function.

  • When this is used as part of automated insulin and glucagon dosing system, it could enable more aggressive insulin dosing to lower average blood sugar more closely to gluco-normals.

Using food to treat a low is much more accessible, simpler, cheaper, and pragmatic. My interest is driven mainly by my curiosity and thinking that its benefits may not be appreciated until many years from now.

The other thing is that your food absorption might be delayed. Like if you have a high fat meal, or your stomach is full, or you are dehydrated, etc. In those situation, food does not absorb quickly. Many times I have treated a low with food and then waited and waited…

As long as your liver is stocked, glucagon is incredibly consistent and quick!

@Terry4, try it, you will like it!

As far as mini-dosing being approved, I am not sure it is even approved for the current glucagon kits. People do it, but has the FDA approved it with the current Lilly glucagon?

The whole approval thing is nonsense. Get whatever shelf-stable glucagon kit you can, put it in a vial. That’s your approval!

As far as cost, I am not sure how it works for everyone’s insurance, but my insurance has always covered the Lilly glucagon kits at an incredibly cheap amount. It’s logical for insurance to to that. If it stops a trip to the ER, glucagon saves the insurance company thousands of dollars. Those ambulance rides are not cheap!

Does glucagon raise blood sugar faster than, say, glucose tablets? Don’t know the answer, but if faster, that could be an advantage.

I personally hate waiting around wondering if the correction I’ve made is adequate. Sometimes if I’m in the low range, dropping quickly, I get a bit paranoid and take more glucose than I need, ending up with a BG spike.

Even though I know it will take several minutes before BG will rise after eating, and that eating ‘more’ doesn’t mean ‘faster’, it’s hard not to over react.

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Regarding mini-dosing, that implies it isn’t an emergency. Even when I’m really, really low, like the low 40’s I can eat and bring my bg’s up without assistance. When one needs assistance it’s tittering on the brink of perhaps needing glucagon if past history shows that person can’t safely eat (choking hazard, or other issues).

To Terry’s comments, a few skittles or 1/2 a banana can bring up bg’s and that’s not a ton of calories, so I think the calorie argument is specious at best.

Agreed, but you’re missing my point. I’m asking is it faster than glucose in
non emergency situations for faster feedback and better control of how much glucose you take as a correction. So back to my original question - is it faster than oral glucose?

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Sometimes eating is faster, sometimes it is not. As mentioned above, it depends on what is going on with your digestive system at the time.

Makes sense that what’s in your digestive tract at the time you eat has an impact. But transit time before uptake in an empty digestive tract is still a factor. I would think that’s still slower than immediate release from your liver?

I really like the idea.
One, I do not need to eat more. I am not fat, but I don’t NEED to eat.
I feel that using this would closely mimic our natural body functions rather than abusing our digestive tract.
NORMAL bodies normally produce too much insulin for any meal, then counterbalance it with a small liver dump to bring your BG back to stability.

Also, when sick, you cannot always eat enough to get your BG back up if you just dosed for a meal, and cannot keep it down.