List of Excipients in Branded Drug GVOKE HYPOPEN

Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
Xeris Pharmaceuticals Inc	GVOKE HYPOPEN	glucagon injection, solution	72065-121	DIMETHYL SULFOXIDE
Xeris Pharmaceuticals Inc	GVOKE HYPOPEN	glucagon injection, solution	72065-121	SULFURIC ACID

GVOKE HYPOPEN Excipient Strategy and Commercial Opportunities

Last updated: August 16, 2026

GVOKE HYPOPEN uses a liquid, ready-to-administer glucagon formulation rather than the conventional powder-and-diluent rescue kit. Its commercial differentiation depends on the combination of glucagon, dimethyl sulfoxide (DMSO), trehalose, an acidic formulation environment, and a single-step autoinjector. The formulation reduces preparation errors, improves caregiver usability, and supports broader distribution through retail pharmacies, schools, emergency kits, and diabetes-management channels.

The principal commercial opportunity is expansion of the severe-hypoglycemia rescue market beyond trained healthcare professionals to caregivers, families, schools, employers, and patients using insulin or other glucose-lowering therapies. The principal competitive risks are low-cost generic glucagon products, nasal glucagon, alternative autoinjectors, formulary restrictions, and patent challenges directed to the liquid formulation or delivery system.

What is GVOKE HYPOPEN and how does its formulation work?

GVOKE HYPOPEN is a single-use autoinjector containing 1 mg of glucagon in a ready-to-use liquid formulation. Xeris Pharmaceuticals, now part of Xeris Biopharma Holdings, developed the product for emergency treatment of severe hypoglycemia in adults and pediatric patients aged 12 years and older weighing at least 45 kg. The product received FDA approval in September 2019 under NDA 212097. [1][2]

The formulation contains:

Component	Functional role
Glucagon	Active pharmaceutical ingredient that raises blood glucose by stimulating hepatic glycogenolysis
Dimethyl sulfoxide	Solubilizing and formulation vehicle that permits liquid glucagon delivery
Trehalose dihydrate	Stabilizer and peptide-protection excipient
Hydrochloric acid and sodium hydroxide	pH adjustment
Water for injection	Aqueous vehicle

The formulation is administered subcutaneously through a prefilled autoinjector. Unlike traditional emergency glucagon kits, the user does not have to reconstitute a powder, attach a needle, or manually draw the dose into a syringe. [1]

Why is DMSO important in GVOKE?

DMSO is the formulation’s key enabling excipient. Glucagon has historically presented stability and solubility challenges in aqueous formulations. DMSO allows Xeris to maintain glucagon in a liquid state at a concentration suitable for a compact rescue device.

The commercial value of DMSO is functional rather than cosmetic. It supports:

• A ready-to-use liquid product
• Elimination of reconstitution
• Reduced preparation time
• A small injection volume
• Compatibility with an autoinjector format
• Potentially improved dose delivery in emergency settings

DMSO also creates regulatory and formulation barriers. A follow-on product must demonstrate acceptable local tolerability, impurity control, container compatibility, extractables and leachables performance, and long-term stability. A competitor cannot assume that substituting another cosolvent will produce an equivalent product.

What role does trehalose play?

Trehalose is commonly used to stabilize proteins and peptides by reducing structural damage during storage. In GVOKE, it supports glucagon stability in the liquid formulation and helps control degradation pathways that could reduce potency or increase impurities.

Trehalose alone does not define the product’s intellectual-property position. The stronger formulation claim is likely to arise from the combination of glucagon concentration, DMSO content, trehalose concentration, pH, stability profile, and delivery-device configuration.

What formulations are protected by GVOKE-related intellectual property?

GVOKE’s defensible technology position is broader than the active ingredient. Glucagon itself is an established peptide and cannot support a conventional composition-of-matter monopoly. Commercial protection instead centers on formulation and delivery.

The relevant protection categories are:

Protection category	Strategic relevance
Liquid glucagon composition	Protects the use of a stable glucagon solution rather than a reconstituted product
DMSO-containing formulation	Can limit direct substitution with the same or similar cosolvent system
Trehalose-containing formulation	Supports peptide stabilization claims
pH and concentration ranges	May protect the operating window needed for stability and tolerability
Container and device compatibility	Covers the interaction between formulation and autoinjector components
Prefilled delivery system	Raises device-sameness and combination-product issues for an ANDA applicant
Method of emergency glucagon administration	May create method-of-use or use-related barriers

Xeris has described a patent estate covering ready-to-use glucagon formulations and drug-delivery systems in its SEC filings. The commercial value of those patents depends on claim scope, terminal disclaimers, patent-term adjustment, prosecution history, and whether the claims survive validity challenges. [3]

A definitive freedom-to-operate analysis requires review of the issued claims, Orange Book listings, continuation applications, terminal disclaimers, and litigation records. The FDA label does not establish the complete patent estate.

When does GVOKE lose exclusivity?

GVOKE’s regulatory exclusivity is separate from its patent protection.

The product is based on glucagon, an established active ingredient. Its primary FDA protection came from approval of a new formulation and delivery system rather than a new molecular entity. The standard five-year new chemical entity exclusivity therefore does not apply.

The relevant exclusivity framework is:

Protection	Expected status
New chemical entity exclusivity	Not applicable because glucagon was previously approved
Three-year clinical-investigation exclusivity	Applied to the new formulation and approval; the period began with the 2019 approval and expired in 2022
Orphan-drug exclusivity	Not identified as the principal GVOKE protection
Patent protection	May extend beyond regulatory exclusivity, depending on issued claims and patent-term calculations
Device protection	May create practical barriers even where drug exclusivity has expired

After the three-year period expired, an applicant could pursue an ANDA or another abbreviated pathway, subject to applicable patents and FDA requirements. Patent expiry dates cannot be determined reliably from the approval date alone.

What is the Orange Book status of GVOKE HYPOPEN?

GVOKE is an FDA-approved drug-device combination product. Orange Book analysis should distinguish between:

1. The glucagon drug formulation.
2. The prefilled syringe or autoinjector presentation.
3. Patents listed against the NDA.
4. Any unlisted formulation, manufacturing, or device patents that may still affect litigation or commercial launch.

An ANDA applicant challenging listed patents would typically use a Paragraph IV certification. If the NDA holder receives timely notice of the Paragraph IV certification and files suit within the statutory period, FDA approval may be subject to a 30-month stay, subject to statutory exceptions and court developments. [4]

The principal Paragraph IV risk areas would be:

• Whether the proposed product contains the same active ingredient and strength
• Whether the formulation uses the same or substantially equivalent excipient system
• Whether the product is therapeutically equivalent
• Whether the autoinjector qualifies as the same delivery device
• Whether the applicant can avoid infringement through different pH, cosolvent, stabilizer, or device parameters

A generic could seek approval for glucagon injection without copying the GVOKE device or formulation. That product would compete with GVOKE commercially but would not necessarily qualify as a direct substitutable equivalent.

What generic entry risks exist for GVOKE?

The highest-risk generic scenario is a product that uses the same or substantially similar liquid glucagon formulation and a comparable single-use delivery system. Such a product could target the same patient and caregiver segment while competing for formulary placement.

The main entry scenarios are:

Scenario 1: Traditional reconstituted glucagon generic

This is the lowest direct threat to GVOKE’s differentiation. The product would compete primarily on price and reimbursement but would retain the preparation burden that GVOKE was designed to remove.

Scenario 2: Ready-to-use liquid glucagon without an autoinjector

This product could offer some convenience advantages while avoiding selected device claims. Its commercial performance would depend on syringe handling, packaging, training, and payer classification.

Scenario 3: Liquid glucagon with a different excipient system

A competitor could attempt to avoid formulation claims by replacing DMSO, trehalose, or both. The technical risk is reduced stability, aggregation, degradation, or inadequate shelf life.

Scenario 4: Copycat autoinjector

This is the most direct commercial threat. It would require close attention to device patents, human-factors data, injection-force performance, dose accuracy, and combination-product requirements.

Scenario 5: Intranasal glucagon

Baqsimi, Eli Lilly’s intranasal glucagon, competes on ease of administration without a needle. It is a branded alternative rather than a conventional generic substitute. [5]

How does GVOKE compare with competing glucagon products?

Product	Route	Preparation	Main commercial advantage	Main limitation
GVOKE HYPOPEN	Subcutaneous autoinjector	None	Ready-to-use, familiar injection format	Requires injection and trained action under stress
GVOKE prefilled syringe	Subcutaneous syringe	None	Ready-to-use and potentially lower device cost	More manual handling than HypoPen
Traditional glucagon emergency kit	Subcutaneous or intramuscular	Reconstitution required	Established and often lower-cost	Multiple preparation steps
Baqsimi	Intranasal	None	Needle-free delivery	Nasal administration and product-specific handling
Generic glucagon kits	Usually injectable	Often reconstitution required	Price and broad availability	Lower convenience

GVOKE’s strongest differentiation is the elimination of reconstitution. Baqsimi’s strongest differentiation is needle-free administration. Traditional glucagon products retain an advantage in price and procurement familiarity.

What commercial opportunities exist for GVOKE excipients?

The excipient strategy creates opportunities beyond the current product.

Pediatric dose expansion

A 0.5 mg ready-to-use presentation can address smaller pediatric patients and reduce dose-measurement errors. Gvoke prefilled syringes include pediatric dosing presentations, while HypoPen’s commercial positioning has focused on the 1 mg dose. [1]

Expanded emergency channels

Potential channels include:

• School nurse and school emergency programs
• Summer camps and youth sports organizations
• Ambulance and first-responder kits
• Pharmacies and retail clinics
• Employer first-aid programs
• Long-term-care facilities
• Diabetes technology starter kits
• Hospital discharge programs
• Insulin pump and intensive insulin-therapy programs

Co-packaging with diabetes therapies

A rescue glucagon product can be bundled with insulin, continuous glucose monitoring, automated insulin delivery, or diabetes education programs. Partnerships with device manufacturers could place GVOKE into onboarding kits for patients at elevated hypoglycemia risk.

Contract manufacturing and licensing

The formulation platform may have value for other unstable peptides requiring rapid emergency delivery. Xeris has commercialized a broader formulation and delivery platform known as XeriSol, which is designed to enable ready-to-use liquid formulations for peptides and other complex molecules. [3]

Potential licensing targets include:

• Emergency hormones
• Peptide antidotes
• Rescue medications
• Biologic products requiring reconstitution
• Hospital drugs with high preparation-error rates
• Specialty products needing compact room-temperature delivery

The most attractive partners would have an established molecule but lack a stable liquid formulation or convenient delivery system.

What manufacturing and IP barriers protect GVOKE?

The manufacturing barrier is the integration of formulation and device processes. Key controls include:

• Glucagon impurity profile
• DMSO and trehalose raw-material specifications
• Solution pH
• Peptide concentration
• Fill volume
• Container closure integrity
• Device dose accuracy
• Injection force
• Stability under temperature excursions
• Compatibility between the formulation and elastomeric or plastic components

A competitor may be able to reproduce the ingredient list but still fail to match shelf life, device performance, or human-factors requirements. These practical barriers can delay market entry even after basic formulation patents expire.

What is the FDA regulatory status of GVOKE?

GVOKE was approved by FDA in September 2019 under NDA 212097 for the emergency treatment of severe hypoglycemia in adults and pediatric patients aged 12 years and older weighing at least 45 kg. FDA later approved additional glucagon presentations for younger and lower-weight pediatric patients. [1][2]

GVOKE is subject to combination-product requirements because the drug and delivery device function together. Regulatory review therefore includes both pharmaceutical quality and device performance.

The key post-approval regulatory risks are:

• Manufacturing changes affecting stability
• Device-component changes
• Human-factors findings
• Dose-delivery failures
• Particulate or degradation-product concerns
• New pediatric or chronic-use indications
• Comparative studies against nasal glucagon or traditional kits

How strong is the GVOKE patent estate?

The estate is strongest where it protects the integrated product: a stable liquid glucagon formulation delivered through a single-use device. It is weaker against products that use a different formulation, a different route, or a different device architecture.

Estate element	Relative strength
Glucagon molecule	Low, because the molecule is established
Liquid formulation concept	Moderate to strong, depending on claim breadth
DMSO and trehalose combination	Potentially strong if claims cover defined ranges and stability results
Autoinjector configuration	Moderate, subject to device-claim validity
Method of use	Variable and vulnerable to prior-art challenges
Manufacturing process	Potentially strong if process parameters are difficult to design around
Commercial know-how	Strong practical barrier but not equivalent to patent exclusivity

Patent strength should be evaluated claim by claim. The most important diligence questions are whether the claims require DMSO, whether they specify trehalose or concentration ranges, whether they cover the device independently, and whether continuation patents remain pending.

Key Takeaways

• GVOKE’s core advantage is a stable, ready-to-use liquid glucagon product that eliminates reconstitution.
• DMSO is the principal enabling excipient; trehalose supports peptide stability.
• The most valuable intellectual property is likely directed to formulation ranges, stability, device integration, and manufacturing controls rather than glucagon itself.
• GVOKE’s three-year regulatory exclusivity did not provide long-term protection because glucagon was previously approved.
• Direct generic risk is highest from a ready-to-use liquid glucagon autoinjector.
• Traditional glucagon kits remain price competitors, while Baqsimi is the principal branded convenience competitor.
• The formulation platform has licensing potential for other emergency peptides and reconstitution-sensitive products.
• Commercial expansion opportunities include schools, first responders, pharmacies, pediatric rescue kits, diabetes-device bundles, and employer emergency programs.

FAQs

Can a competitor copy GVOKE by using the same glucagon dose?

Yes, potentially. The active ingredient and dose alone do not define GVOKE. A competitor must address formulation, stability, delivery-device, therapeutic-equivalence, and patent requirements.

Is DMSO in GVOKE a safety or commercialization barrier?

DMSO is both an enabling excipient and a development constraint. Its use requires control of tolerability, formulation compatibility, impurities, and container interactions, but it also supports the liquid product’s primary convenience advantage.

Could a generic glucagon product receive automatic pharmacy substitution for GVOKE?

Not necessarily. Substitution depends on FDA therapeutic-equivalence ratings, dosage form, delivery device, formulation equivalence, and state pharmacy law. A reconstituted glucagon kit would not automatically be interchangeable with an autoinjector.

Does GVOKE have biosimilar competition?

No. GVOKE is a glucagon drug product, not a biologic subject to the biosimilar pathway. Competition would generally arise through generic, hybrid, 505(b)(2), or branded alternative pathways.

Which GVOKE presentation has the strongest commercial growth potential?

The autoinjector has the strongest convenience proposition for caregivers and community settings. The prefilled syringe may have greater procurement flexibility where device cost, pediatric dosing, or institutional administration practices are more important.

References

1. U.S. Food and Drug Administration. (2024). GVOKE (glucagon injection) prescribing information.
2. U.S. Food and Drug Administration. (2019). Approval letter for NDA 212097: GVOKE glucagon injection.
3. Xeris Biopharma Holdings, Inc. (2024). Annual report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934.
4. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
5. U.S. Food and Drug Administration. (2019). BAQSIMI (glucagon nasal powder) prescribing information.