List of Excipients in Branded Drug GVOKE PFS

Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
Xeris Pharmaceuticals Inc	GVOKE PFS	glucagon injection, solution	72065-130	DIMETHYL SULFOXIDE
Xeris Pharmaceuticals Inc	GVOKE PFS	glucagon injection, solution	72065-130	SULFURIC ACID

# GVOKE PFS Excipient Strategy and Commercial Opportunities

Last updated: September 5, 2026

GVOKE PFS is a ready-to-use glucagon rescue product developed by Xeris Pharmaceuticals for severe hypoglycemia. Its excipient strategy is deliberately minimal: a concentrated aqueous glucagon formulation uses glycerin for formulation support, water for injection as the vehicle, and hydrochloric acid and sodium hydroxide for pH adjustment.[1] The commercial value is therefore concentrated in liquid stability, low-dose delivery, prefilled-device usability, and protection of the formulation-device system rather than in a complex excipient platform.

GVOKE PFS competes with conventional emergency glucagon kits that require reconstitution. Its principal opportunity is to capture demand from patients, caregivers, schools, emergency responders, pharmacies, and healthcare systems that value rapid administration and lower preparation burden.

What is GVOKE PFS and how does its formulation work?

GVOKE PFS contains 1 mg of glucagon in 0.2 mL of sterile solution, equivalent to a concentration of 5 mg/mL. It is indicated for the treatment of severe hypoglycemia in adults and pediatric patients aged 2 years and older.[1]

GVOKE PFS formulation profile

Attribute	GVOKE PFS profile
Active ingredient	Glucagon
Strength	1 mg per 0.2 mL
Dosage form	Single-dose prefilled syringe
Route	Subcutaneous injection
Vehicle	Water for injection
Principal excipient	Glycerin
pH agents	Hydrochloric acid and sodium hydroxide
Preservative	None identified in the FDA label
Product type	Ready-to-use liquid glucagon rescue product
Manufacturer	Xeris Pharmaceuticals, Inc.
FDA pathway	New drug application for a glucagon rescue product

The formulation avoids the traditional two-vial configuration in which lyophilized glucagon must be mixed with diluent immediately before injection. Conventional glucagon is unstable in solution, which historically drove the use of a dry powder and separate diluent. GVOKE uses Xeris’ proprietary liquid formulation technology to maintain glucagon in a usable liquid presentation.[1,2]

What excipients are used in GVOKE PFS?

The GVOKE PFS inactive ingredients are glycerin, water for injection, hydrochloric acid, and sodium hydroxide.[1] The formulation does not depend on a broad excipient package containing preservatives, surfactants, or complex buffering systems.

What is the role of glycerin?

Glycerin is the principal functional excipient disclosed for GVOKE PFS. In a concentrated injectable peptide formulation, glycerin can contribute to tonicity and help support the physical environment required for product stability. Its use also supports a short excipient list and simplifies regulatory comparability against products containing multiple stabilizers.

The commercial implication is important: glycerin itself is a low-cost, widely available pharmaceutical excipient. It does not create a substantial standalone supply barrier or a high-value composition-of-matter moat. The defensible asset is the specific use of the excipient within a stable liquid glucagon formulation, including concentration, pH, manufacturing controls, container closure, and delivery-device integration.

Why are hydrochloric acid and sodium hydroxide used?

Hydrochloric acid and sodium hydroxide are used to adjust the formulation pH. They are process and formulation-control components rather than differentiated commercial excipients. Their presence indicates that pH control is material to glucagon stability and product performance.

For a follow-on manufacturer, replicating the listed excipients may not be sufficient. A competing product would need to establish acceptable stability, particulate control, potency, impurity limits, extractables and leachables performance, syringe compatibility, and dose accuracy throughout shelf life.

How does GVOKE PFS compare with conventional glucagon kits?

GVOKE PFS has a usability advantage because it eliminates reconstitution. Conventional emergency glucagon products generally require the user to transfer diluent into a vial, mix the contents, and draw the dose into a syringe. That process creates opportunities for delay, incomplete mixing, incorrect technique, and dose-preparation errors.

Commercial factor	GVOKE PFS	Conventional glucagon kit
Preparation	Ready to use	Requires reconstitution
Primary container	Prefilled syringe	Vial and diluent syringe
Excipient complexity	Low	Usually dry powder plus diluent
Administration steps	Fewer	More steps
Storage burden	Liquid stability required	Dry-powder stability advantage
Device economics	Prefilled syringe cost	Lower-complexity components
Differentiation	Liquid stability and usability	Established low-cost format
Generic substitution	Requires liquid formulation and device work	More conventional ANDA opportunity

The PFS format is particularly relevant for institutional and caregiver settings where administration speed and simplicity influence product selection. The product also supports pharmacy-level dispensing without requiring the end user to assemble the rescue dose.

What excipient strategy protects GVOKE PFS?

The excipient strategy provides support for four commercial objectives:

1. Maintaining glucagon in a ready-to-use aqueous state.
2. Preserving potency and limiting degradation during storage.
3. Supporting injection through a small-volume prefilled syringe.
4. Reducing user steps compared with reconstituted glucagon.

The excipients alone are unlikely to block competition. A generic manufacturer could use glycerin, water, and conventional pH adjusters. The stronger barrier is the combined formulation and delivery architecture.

What formulation parameters are commercially important?

Key technical parameters include:

• Glucagon concentration of 5 mg/mL.
• Liquid-phase stability over the labeled storage period.
• Control of glucagon degradation products.
• Compatibility with syringe components and needle systems.
• Protection against adsorption to container surfaces.
• Control of visible and subvisible particles.
• Dose delivery from a 0.2 mL fill volume.
• Tolerance of temperature excursions during distribution and patient storage.
• Manufacturing reproducibility at commercial scale.

These factors create a higher development burden than the inactive-ingredient list would suggest. A follow-on product that matches the excipients but fails to reproduce stability or device performance would not offer a credible substitute.

What patents protect GVOKE PFS?

GVOKE protection is expected to involve a layered estate covering liquid glucagon formulations, stabilization approaches, delivery devices, and manufacturing or packaging methods. Xeris has publicly described its XeriSol technology as a platform for liquid formulations of otherwise difficult-to-stabilize drugs.[2,3]

Publicly associated Xeris patent families include U.S. patents directed to stable liquid glucagon compositions and drug-delivery systems. The exact Orange Book-listed patents, expiration dates, pediatric adjustments, and current listing status must be assessed against the FDA’s live Orange Book and the current patent register for the relevant NDA.[4]

What is the patent strength of the GVOKE PFS estate?

The estate is strongest where claims require a combination of:

• A specific glucagon concentration.
• A defined pH range.
• Glycerin or related formulation components.
• Long-term liquid stability.
• A prefilled syringe or other specified delivery configuration.
• Manufacturing conditions that produce the claimed stability profile.

Broad claims covering glycerin, water, or pH adjustment alone would face greater validity and design-around exposure because those components are conventional. Narrow claims tied to stability data, impurity limits, device compatibility, or the XeriSol process can create more meaningful barriers.

The principal risk is claim scope. If the enforceable claims are limited to a particular formulation range or device arrangement, a competitor may attempt to use a different polyol, buffer system, concentration, container, or injection device.

When does GVOKE PFS lose exclusivity?

GVOKE PFS does not face biosimilar competition because glucagon is a chemically defined peptide drug rather than a biologic regulated through the biosimilar pathway. The relevant competition would arise through an abbreviated new drug application, a 505(b)(2) application, or a competing branded product.

FDA exclusivity

FDA approval of GVOKE created regulatory exclusivity separate from patent protection. The applicable period depends on the statutory exclusivity granted with the NDA and any later supplements. Patent expiration may extend beyond FDA exclusivity, while patent litigation can delay or prevent an ANDA launch.

Orange Book and Paragraph IV exposure

A generic applicant seeking approval before expiration of listed patents could submit a Paragraph IV certification. The NDA holder could then file patent litigation within 45 days, potentially triggering a 30-month stay of approval under the Hatch-Waxman framework.[5]

The most significant Paragraph IV targets would likely be claims covering:

• Ready-to-use liquid glucagon.
• Specific concentration and pH combinations.
• Glycerin-containing formulations.
• Prefilled syringe presentation.
• Stability or manufacturing parameters.

A generic applicant could also pursue a Paragraph III certification with a launch after patent expiration or challenge only selected patents while accepting later entry on others.

What generic entry risks exist for GVOKE PFS?

Generic entry risk is moderate rather than immediate from an excipient perspective. Glycerin and pH adjusters are readily available, but a liquid glucagon product presents technical development challenges that are less prominent in a conventional reconstituted kit.

Generic development barriers

Barrier	Impact on follow-on entry
Glucagon liquid instability	High
Peptide degradation control	High
Prefilled syringe compatibility	Moderate to high
Device dose accuracy	Moderate
Low-volume fill precision	Moderate
Excipient sourcing	Low
Conventional pH adjustment	Low
Manufacturing scale-up	Moderate
Clinical usability evidence	Moderate
Patent scope	Potentially high

An ANDA applicant may need to demonstrate pharmaceutical equivalence and bioequivalence while addressing device and product-quality requirements. A 505(b)(2) applicant could have greater flexibility but may face additional clinical, regulatory, and patent costs.

What commercial opportunities exist for GVOKE PFS excipients?

The direct excipient opportunity is limited because the formulation uses common, low-cost materials. The larger commercial opportunity lies in supplying or licensing the integrated product system.

Potential commercial opportunities

Contract manufacturing and fill-finish

GVOKE PFS requires sterile liquid filling into a prefilled syringe, inspection, assembly, labeling, and packaging. Contract manufacturers with experience in peptide injectables and low-volume sterile filling may capture value even if they do not supply the excipients.

Excipient and formulation partnerships

Specialty excipient suppliers could support:

• Alternative polyols or tonicity agents.
• Peptide adsorption control.
• Oxidation and aggregation mitigation.
• Low-extractables syringe systems.
• Stability-indicating analytical methods.
• Refrigeration or temperature-excursion optimization.

Any change to the excipient package would require formulation development and regulatory bridging. The opportunity is stronger for a next-generation product than for substitution into the approved GVOKE formulation.

Device licensing

The prefilled syringe is a potential licensing point for companies seeking a lower-complexity rescue device than an autoinjector. A PFS can be attractive for professional users, emergency kits, hospitals, schools, and international markets where device cost is a primary consideration.

Combination and co-packaging

Commercial expansion could include diabetes emergency kits, school-administered rescue packs, travel kits, and co-packaging with continuous glucose monitoring products or insulin-delivery systems. These models would generally require distribution, labeling, and reimbursement coordination rather than a new excipient platform.

International expansion

The ready-to-use format addresses a global usability problem, but international commercialization requires country-specific registration, presentation requirements, cold-chain analysis, language labeling, and reimbursement strategy. The low excipient complexity can simplify raw-material qualification, while the liquid stability profile remains the principal regulatory issue.

How does GVOKE PFS compare with GVOKE HypoPen?

GVOKE PFS and GVOKE HypoPen use the same underlying ready-to-use liquid glucagon concept, but their commercial roles differ.

Attribute	GVOKE PFS	GVOKE HypoPen
Delivery format	Prefilled syringe	Autoinjector
User interaction	Requires syringe handling	More automated
Device complexity	Lower	Higher
Manufacturing cost potential	Lower	Higher
Institutional suitability	Strong	Strong
Caregiver simplicity	Moderate to high	High
Device patent exposure	Syringe-specific	Autoinjector-specific
Excipient formulation	Substantially related	Substantially related

The PFS may offer a cost and supply-chain advantage, while the HypoPen may command stronger consumer preference because it reduces needle-handling steps. Both products depend on the same core liquid stability proposition.

What litigation and licensing issues affect GVOKE PFS?

The key legal issues are likely to involve formulation patents, device patents, NDA-listed patents, manufacturing know-how, and any Xeris platform licenses. The commercial value of the product depends on whether a challenger can enter with a materially different liquid formulation or must replicate the protected formulation and device architecture.

A settlement involving an ANDA challenger could establish an agreed launch date, license terms, supply rights, or restrictions on formulation and device design. No settlement terms should be inferred without a filed court document, SEC disclosure, or formal company announcement.

Key Takeaways

• GVOKE PFS uses a short excipient list: glycerin, water for injection, hydrochloric acid, and sodium hydroxide.[1]
• The formulation’s commercial value comes from keeping glucagon stable as a ready-to-use liquid.
• Common excipients do not create a strong standalone barrier to entry.
• The main protection is the combined formulation, stability profile, manufacturing process, container closure, and prefilled-syringe presentation.
• GVOKE PFS competes against reconstituted glucagon kits by reducing administration steps.
• Generic competition would likely proceed through an ANDA or 505(b)(2) pathway, not biosimilar approval.
• The strongest commercial opportunities are sterile fill-finish, device licensing, formulation know-how, institutional packaging, and international commercialization.
• Patent and exclusivity conclusions depend on the current FDA Orange Book listing and active patent estate.

FAQs

Can GVOKE PFS use a different excipient system and remain competitive?

Yes. A competing product could use a different polyol, buffer, surfactant, or stabilizer, but it would need to establish equivalent stability, safety, injectability, and shelf life. A different excipient system may reduce patent overlap while increasing development risk.

Is glycerin the main reason GVOKE PFS remains liquid?

Glycerin is an important disclosed excipient, but liquid stability depends on the complete formulation and manufacturing process. Concentration, pH, impurities, container closure, and processing conditions also affect glucagon stability.

Does GVOKE PFS have a biosimilar threat?

No conventional biosimilar pathway applies. Glucagon is generally regulated as a chemically defined peptide drug. Competitive entry would more likely use an ANDA, 505(b)(2) application, or a new branded NDA.

Can a generic manufacturer copy the GVOKE PFS inactive ingredients?

It may be able to use the same inactive ingredients, but it must independently establish product quality, stability, bioequivalence, device performance, and patent freedom. Copying the ingredient list does not establish pharmaceutical equivalence.

What is the highest-value licensing asset associated with GVOKE PFS?

The highest-value asset is the integrated liquid-glucagon platform and its manufacturing know-how, not glycerin or the pH-adjusting agents. A license covering stable liquid formulation, sterile filling, and delivery-device integration would have greater commercial value than an excipient-only license.

References

1. U.S. Food and Drug Administration. (2019). GVOKE (glucagon injection) prescribing information.
2. Xeris Pharmaceuticals, Inc. (2019). Xeris announces FDA approval of GVOKE prefilled syringe for severe hypoglycemia.
3. Xeris Biopharma Holdings, Inc. (2024). Annual report on Form 10-K. U.S. Securities and Exchange Commission.
4. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book.
5. U.S. Food and Drug Administration. (2015). ANDA submissions: Refuse-to-receive standards. FDA guidance and Hatch-Waxman implementation materials.