FDA OKs First Needle-Free Nasal Glucagon

Huge news for those of us whose lives depend on insulin: After years of R&D and community anticipation, we now have a new form of glucagon, the emergency blood sugar boosting substance, that can simply be sprayed up the nose rather than requiring a complicated mix kit and scary-large needle that bystanders have to stab you with.

Remarkably, this is the first new type of glucagon we've seen since the standard injectable emergency kits were introduced in 1961!

On July 24, the FDA announced its approval of the new intranasal glucagon known as Baqsimi (more on the name in a moment), made by pharma giant Eli Lilly. That company is of course a major insulin manufacturer, but also makes one of the two multi-step, injectable glucagon kits currently available (the other being Novo Nordisk). Originally developed by a Canadian biomed company, the new nasal glucagon was acquired by Lilly in 2015 and has been in late stage clinical trials since being submitted to regulators a year ago in June 2018.

While it may seem a bit dramatic to describe this new drug as "historic" and "game-changing," it's certainly a milestone for our community as it's the first new type of glucagon to hit the market since the original injectable forms were introduced almost six decades ago. In fact, Lilly's new product will be available starting in August 2019 it's the first of three new forms of glucagons expected to hit the market in the near future, setting the stage for new ways of using glucagon.

JDRF CEO Dr. Aaron Kowalski, who lives with T1D himself, issued the following statement: “This is an important step toward providing more treatments to address the complications of type 1 diabetes. Until now, complex glucagon injections that take several steps to administer were the only available treatment for people experiencing a severe hypoglycemic episode. Administering nasal glucagon is a much less invasive and simplified process that can save critical moments during an emergency, particularly if an individual loses consciousness. JDRF is grateful to FDA for its decision and continues to advocate for more treatments to come to market so that people with T1D can better manage its complications and live happier and healthier lives.”

Baqsimi Nasal Spray: The Basics and How It Works

As a reminder, glucagon is a hormone that triggers the liver to release glucose very quickly in order to boost blood sugar levels. The familiar red and orange multi-step glucagon emergency kits have been the only option to date (and Lilly says it will continue to offer those).

Here's a snapshot of this new Baqsimi product, including cost and what's ahead for the glucagon market:

• Ready-to-Use Dispenser: This is a 3 mg dose of glucagon that's for a single use, housed in a compact, portable, ready-to-use plastic dispenser. The full dose is used up upon acting, so this doesn't allow for mini-dosing (which is not yet FDA OK'd, but done by many patients off-label using traditional injectable glucagon). Interestingly, the dispenser is actually developed by Illinois-based company AptarGroup, which maufacturers this Unidose Device for multiple powder-form drugs beyond just glucagon and diabetes.

• Dosing: The dispenser tip is inserted into a nostril and you press/squeeze a small plunger on the bottom of the device to release the foxed dose of glucagon dry powder into the nose. That glucagon is then absorbed into the nasal cavity lining, where it starts working immediately. No inhaling, sniffing, or deep-breathing is required -- especially important if the PWD (person with diabetes) is unconscious or not fully aware of what's happening. See Lilly's online instruction guide here.

• Mini-Dosing: Not with Baqsimi, Lilly says. This is a once-and-done dispenser, where you use the full 3 mg dose at one time. You push the plunger until the green line disappears, indicating 100% of the dose has been given. The company says it hasn't explored glucagon mini-dosing to date because it has been focused on this easer-to-use emergency rescue glucagon.

• With a Cold or Congestion: Yes, it works even if you have a common cold and/or nasal congestion, and are taking meds for those particular symptoms. Clinical trial data shows this glucagon is just as effective in those situations.

• Clinical Data: Speaking of trials, in two clinical studies of 83 and 70 adults with diabetes comparing a single dose of Baqsimi to a single dose of injectable glucagon, Baqsimi was significantly more effective. It started working within minutes and boosted blood sugar levels completely within 15-30 minutes. In a pediatric study of 48 patients over 4 years old, similar results were observed.

• Kids and Adults: Baqsimi is approved for both adults and kids, ages 4 and up. There will be ongoing safety and efficacy studies for children younger than 4, as well. Lilly says the same 3 mg dosing is safe for any of those ages, whether it be a full-grown male or a small child.

• Side Effects: There are no notable black box warnings, but possible side effects mirror many of those included on injectable glucagon products currently -- watery eyes, redness and itchiness of the eyes, nausea, vomiting, headache, etc. There are also a few conditions and other meds that can influence Baqsimi's effectiveness, including insulinoma or pheocromocytoma, and beta blockers or indomethacine drugs. The interfering ingredients include betadex and dodecylphosphocholine. Also, since glucagon's effectiveness can be impaired by alcohol (due to the liver's need to deal with alcohol vs. glucose dumping), that remains an item to keep in mind when using Baqsimi.

• Storage: Shelf life is 18 months to 2 years, and Lilly says it's working on extending that expiration date. Baqsimivdoes not require refrigeration and should be stored up to 86 degrees. It comes packaged in a tube with shrink wrap, and you're supposed to keep it in that tube prior to use. Lilly says that exposure to moisture could impair the nasal glucagon's effectiveness.

• Availability: Baqsimi will be for sale in pharmacies starting in August 2019. A prescription will be required, meaning this will not be available over-the-counter (OTC). More specifics on access and pricing is below. 

For those interested in more FDA detail on Baqsimi, the agency has posted its official letter to Eli Lilly as well as the 18-page labeling documentation for review.

Puffing Glucagon Up Your Nose

Remember, Basqimi is the same nasal glucagon that I got to trial-test in prototype form back in 2014, before Lilly acquired the product. My experience was as follows:

After being put on an insulin drip to drop my glucose levels into the 50s and 40s, I was prompted to administer the investigational glucagon up my nose. I felt like it started working within a few minutes -- certainly much quicker than the normal injectable glucagon I'd been forced to use just a month earlier. Within 15 minutes, all of my low sensations had passed and my CGM and the clinic's fingerstick readings showed my sugars were on the rise. Within a couple of hours, my BG levels returned to the low 200s, where they'd been hovering before the experiment.

Of course, many others participated in that trial and others through the years. We were also fascinated to eventually see "real life" studies showing the ease-of-use for PWDs and caregivers who might need to resort to this glucagon in an emergency situation. All of that provided proof that this nasal glucagon is much easier to use and just as effective than what we've had available all these years.

Nasal Glucagon Baqsimi: What's in a Name?

It's pronounced "BACK-see-mee," and Lilly acquired the name along with the product itself during the 2015 acquisition from Canada-based startup Locemia Solutions -- whose company name is a mashup of “low blood sugar” and “hypoglycemia." We're told the original inspiration for the name Basqimi came from conversations within the Diabetes Community about "who has your back" when it comes to people helping during scary low blood sugar emergencies.

Locemia was led by Robert Oringer, an entrepreneur with a long history in the diabetes industry and a D-Dad himself with two sons who developed T1D a month apart in 1997. His resume includes a number of diabetes care products, including work in creating the popular Dex4 glucose tabs (which are now discontinued in the USA, at least). He and researchers began working on this intranasal glucagon formulation in 2010.

The group hoped to raise public awareness on hypoglycemia and shift how glucagon's viewed, so that it might be more visible with treatments readily available, like defibrillators and the EpiPen in restaurants, stadiums, schools, and other public places.

"I’m very grateful to everyone who contributed over so many years to the development of this amazing and vitally important product -- including our small but mighty team at Locemia, the researchers who ran our clinical trials, insulin users who volunteered to be part of our trials, scientific advisors, patient advocates, investors, and countless others," he wrote in an email.

"Claude Piche, Co-Founder and CEO of Locemia, and I are both beyond grateful to the team at Eli Lilly that recognized the value of Baqsimi over five years ago and showed their commitment by taking the action to acquire it, continue to invest in it, and bring it forward to market. You cannot begin to imagine the number of talented Lilly team members who have contributed to this moment and are continuing to work to bring Baqsimi to the world. Yes, the U.S. will be first, but hopefully Canada (where the development took place), Europe, and other countries will have Baqsimi available for insulin users and those who love or care for them."

Access and Affordability for Baqsimi Glucagon

Lilly says it expects Baqsimi to be available in U.S. pharmacies starting by end of August (2019), and they've already submitted it to regulatory agencies in Canada, Europe and Japan where it's still being reviewed.

We're told that Baqsimi will have the same list price as Lilly's injectable glucagon emergency kit: $280.80 for a single dispenser, and a two-pack will cost $561.60.

That's disappointing.

Many in the D-Community had hoped this new form of glucagon would be more affordable, rather than being just as unafforable as a vial of insulin in the U.S. these days. While insulin pricing and diabetes device access have been in the news lately, the price of glucagon has remained less-discussed in our D-Community and beyond.

When queried about concerns over the high list price, a Lilly spokesperson told us the company is offering a Baqsimi Savings Card through the end of 2020 for those with commercial insurance to obtain 2 Baqsimi one-packs or 1 two-packs, for as little as $25. That will be good for 12 months, meaning the card will be good for a year and can be used as many times as you get a new Baqsimi prescription. They also have a first-fill offer where some can get a single Baqsimi product or a 2-pack for no cost, before the savings program kicks in for any refills. This "Got Your BAQ" program will be for those "eiligible," meaning there will be specific criteria. They also referred to further savings cards, Patient Assistance Programs (PAPs) and their Lilly Solutions Center created to offer financial help to those who are eligible for diabetes medications, including insulin and glucagon.

"We understand the financial impact that managing diabetes has on families. Lilly is committed to helping make Baqsimi affordable and accessible to as many people living with diabetes as possible by securing access with payers as well as through our affordability offerings," said Tony Ezell, Lilly's VP of U.S. Connected Care and Insulins.

When asked what the patient community may have expected from Lilly on glucagon pricing, we at the 'Mine told them clearly that this price point will likely be seen by the community as tone-deaf, and it will mean nasal glucagon remains off-limits to a huge swath of patients.

Of course, some insurance plans may very well cover this new Baqsimi glucagon. And the two-pack option may allow people to get twice the amount for a single co-pay. That's all TBD, as Lilly works with insurance companies and Pharmacy Benefit Managers (PBMs) to get this new glucagon included on formularies.

It's also important to know that two other novel glucagon formulations are in the works and one is currently before the FDA:

• Xeris Pharmaceuticals: This Chicago company has developed a single-use hypo rescue pen called G-Voke, filed with FDA in Summer 2018. That's a first-gen product in a form much like the EpiPen, and the FDA is likely to make a decision on that by year's end 2019. Xeris is also working on a next-gen version that will allow for mini-dosing beyond emergency hypo response.

• Zealand Pharma: This Denmark-based company is developing a novel version called Dasiglucagon, a soluble glucagon formula that can be used in insulin pumps. It's being tested in the exciting in-development iLET Bionic Pancreas closed loop system. Dasiglucagon is also being developed in a ready-to-use rescue pen much like the Xeris form factor. Zealand now says it plans to file its stable glucagon formulation with FDA in early 2020. 

Calling for Help on Glucagon Access

Around our D-Community online, responses are mixed on Baqsimi.

Most agree that it's certainly big news and worthy of celebration, given the easy new delivery form. We've seen some note that it could revolutionize how glucagon is viewed and understood by the general public.

But the issue of affordability and access (or lack thereof) is sort of dark cloud, with sentiments like this Tweet from longtime type 1 Chris Wilson in California: "I hope Xeris and/or Zealand eats Lilly's lunch with their shelf-stable liquid formations. The potential of micro-dosing liquid vs intranasal alone opens up VASTLY more applications."

On the advocacy front, there's a recognized need for better glucagon policies -- for schools, nurses, and even paramedics. Maybe now with a non-injectable version that's incredibly easy to use, some policy changes can happen to get glucagon rescue dispensers into more public places and to those who need them most.

For our part, we're thrilled to see an easier, gentler way to treat hypoglycemia emergencies, and we're thankful to all the scientists and leaders who've made this happen.

At the same time, we hope Lilly listens to this commnity feedback calling for help on affordability and access to this important innovation in emergency glucagon treatment for severe hypos.

This breaking news article was originally published on DiabetesMine.