Comprehensive Report on GV-328 Lozenges for Pediatric Oral Aphthosis

1. Executive Summary

• Overview: GV-328 is the investigational designation for a lozenge formulation developed for the management of oral aphthosis (canker sores) in children. The active components of these lozenges are hyaluronic acid and zinc. Clinical evaluation, notably the NCT04677062 study, has explored its efficacy and safety in a pediatric population. Evidence suggests that this formulation is commercially available under the brand name "Oralchup," marketed by Laboratorios Viñas as a dietary or food supplement.[1]
• Key Findings: The primary clinical study (NCT04677062) involving GV-328 lozenges reported statistically significant reductions in pain intensity, lesion size, and associated functional limitations in children aged 3 to 13 years suffering from oral aphthae. Furthermore, the product demonstrated a favorable safety profile, with minimal adverse events, and was generally well-accepted by the pediatric participants, an important consideration for formulations intended for children.[1]
• Overall Assessment: Based on the available evidence, GV-328 lozenges (Oralchup) represent a potentially useful supportive treatment for symptomatic relief of acute oral aphthosis in children. Its classification as a dietary supplement means it is not subject to the same rigorous approval pathways as pharmaceutical drugs. The clinical evidence, while positive, stems from an open-label, non-controlled study, which should be considered when evaluating its efficacy relative to natural resolution or other interventions.
• Focus of the Report: It is imperative to note that this report focuses exclusively on the GV-328 lozenge formulation containing hyaluronic acid and zinc for pediatric oral aphthosis. The "GV-328" designation, or similar numerical identifiers, appears in scientific literature in association with entirely unrelated entities, including microRNAs and other investigational drugs for different therapeutic areas. This report will clearly distinguish the subject product from these homonyms to prevent any confusion.

2. Introduction to GV-328 and Oral Aphthosis

• Definition of GV-328: In the context of this report, GV-328 refers to an investigational lozenge product specifically formulated with hyaluronic acid (5 mg per lozenge) and zinc (1 mg per lozenge). This formulation was the subject of a clinical trial, NCT04677062, designed to assess its safety, galenic acceptability, and efficacy in treating oral aphthosis in children.[1]
• Clarification of Terminology and Differentiation from Homonyms: The designation "GV-328" or similar numerical and alphabetical combinations appear in diverse research contexts, necessitating a clear distinction. The GV-328 discussed herein is unique to the pediatric oral aphthosis lozenge. Other entities include:
• miR-328: A microRNA, which is a small non-coding RNA molecule involved in the regulation of gene expression. miR-328 has been studied in contexts such as endothelial-to-mesenchymal transition in response to high glucose and in the proliferation of certain cancer cells.[3] This is a molecular biological entity, not a pharmaceutical product.
• HPN328 (MK-6070): An investigational trispecific T-cell activating immunotherapy. It is designed to target Delta-like Canonical Notch Ligand 3 (DLL3) and is being evaluated in clinical trials for advanced cancers, including small cell lung cancer and other solid tumors expressing DLL3.[5] Its mechanism and therapeutic area are entirely different from the GV-328 lozenge.
• GLI-328: This refers to an experimental gene therapy approach that utilized herpes simplex virus thymidine kinase gene vector-producer cells followed by ganciclovir administration, investigated for the treatment of recurrent glioblastoma multiforme.[8] This involves cellular therapy and a distinct complex biological mechanism.
• CNTO 328 (Siltuximab): An anti-interleukin-6 (IL-6) chimeric monoclonal antibody. Siltuximab is approved for conditions such as multicentric Castleman's disease and has been investigated for other IL-6 mediated diseases.[9] This is a biologic drug with a specific immunological target.
• Other non-relevant mentions, such as government forms (e.g., SF-328, a "Certificate Pertaining to Foreign Interests" [10]) or general drug rating lists that might coincidentally list drugs with "GV" prefixes [12], are unrelated to the product under review. The clear differentiation of the GV-328 lozenge from these unrelated entities is fundamental for an accurate understanding of its specific characteristics and clinical development.
• Oral Aphthosis (Aphthous Stomatitis / Canker Sores) in the Pediatric Population: Oral aphthosis, commonly known as aphthous stomatitis or canker sores, is a prevalent condition characterized by the recurrent development of painful, shallow ulcers on the non-keratinized oral mucosa.13 In children, these lesions can cause significant discomfort, leading to difficulties with eating, drinking, and speaking, and may result in general irritability and distress. The etiology of oral aphthosis is often multifactorial and can include local trauma, nutritional deficiencies (iron, zinc, folic acid, vitamin B12), genetic predisposition, stress, and associations with certain systemic conditions.14 Given the impact on quality of life, particularly in the pediatric population, there is a continuous need for treatment options that are not only effective in alleviating symptoms and promoting healing but are also safe, well-tolerated, and child-friendly in their administration. The clinical study by Guinot Jimeno et al. on GV-328 lozenges specifically addresses this need by evaluating a novel formulation in children.1

3. Composition and Formulation of GV-328 Lozenges

The GV-328 product evaluated in clinical trials is a specifically designed lozenge intended for topical application within the oral cavity.

• Active Ingredients:
• Hyaluronic Acid (HA): Each lozenge contains 5 mg of hyaluronic acid.[1] HA is a naturally occurring glycosaminoglycan and a major component of the extracellular matrix in connective tissues. It is well-known for its high viscosity in aqueous solutions and its exceptional ability to bind and retain water molecules, contributing to tissue hydration and lubrication.[16]
• Zinc: Each lozenge incorporates 1 mg of zinc.[1] Zinc is an essential trace mineral that plays a vital role in numerous biological processes, including immune system function, wound healing, cell division, and the maintenance of epithelial tissue integrity.[2]
• Formulation Details:
• Dosage Form: The product is formulated as a lozenge, designed to be dissolved slowly in the mouth, much like a "buccal candy".[1] This mode of delivery is critical for ensuring prolonged contact of the active ingredients with the affected oral mucosa, thereby maximizing their local therapeutic effects.
• Plastic Support: A notable feature of the GV-328 lozenge is the inclusion of a plastic support. This component is designed to prevent the child from swallowing the lozenge immediately, ensuring its gradual dissolution and release of active ingredients directly at the site of the oral aphthae.[1] This design element is particularly important in pediatric formulations, enhancing both the efficacy through sustained local action and safety by reducing the risk of accidental ingestion of the whole lozenge.
• Galenic Acceptability: The clinical trial NCT04677062 specifically assessed the galenic acceptability of the lozenges in children.[1] While generally well-accepted, the product's taste was noted as a factor in a few instances of mild nausea at the beginning of treatment.[1] The commercial product, Oralchup, which appears to be GV-328, is described as having a "good taste" to enhance appetisingness.[2]
• Manufacturer and Potential Commercial Product:
• The clinical study NCT04677062 was financed by Laboratorios Viñas, a pharmaceutical company based in Spain.[1]
• The Spanish publication detailing the study refers to GV-328 as being "currently commercialized as a dietary supplement".[1]
• Laboratorios Viñas markets a product named "Oralchup." The description of Oralchup—a lozenge containing hyaluronic acid and zinc, featuring a plastic support, and indicated for mouth sores—aligns precisely with the characteristics of the GV-328 lozenge evaluated in the clinical trial.[2] This strongly indicates that GV-328 is the investigational or research name for the commercially available product Oralchup. The deliberate design of GV-328 as a slow-dissolving lozenge with a plastic support reflects a thoughtful approach to pediatric formulation, aiming to optimize local drug delivery to oral ulcers while ensuring ease of use and compliance in children.

4. Mechanism of Action

The therapeutic effects of GV-328 lozenges in the management of oral aphthosis are attributed to the combined actions of its active ingredients, hyaluronic acid and zinc, delivered topically to the oral mucosa.

• Hyaluronic Acid (HA):
• Mucosal Protection and Hydration: Hyaluronic acid is a high molecular weight polysaccharide that is a primary component of the extracellular matrix. Its hygroscopic nature allows it to attract and retain large amounts of water, contributing to the viscoelasticity and hydration of tissues.[16] When applied topically in the oral cavity, HA can form a protective, bioadhesive film or barrier over the surface of aphthous ulcers. This film shields the exposed nerve endings from mechanical irritation (e.g., from food, tongue movement) and chemical irritants in the oral environment, thereby alleviating pain. Furthermore, by maintaining a moist environment, HA can facilitate the natural healing processes.[13]
• Wound Healing and Anti-inflammatory Properties: HA plays an active role in all phases of wound healing, including inflammation, proliferation, and remodeling. It can modulate inflammatory responses, promote angiogenesis, and stimulate the migration and proliferation of fibroblasts and keratinocytes, which are essential for tissue repair.[13] Studies have demonstrated its efficacy in treating edema and wounds due to these properties.[16]
• Relevance to Oral Aphthosis: In the context of oral aphthous ulcers, HA's barrier-forming capacity, coupled with its anti-inflammatory and wound-healing properties, can lead to a reduction in pain, accelerated healing, and a decrease in the overall duration of the ulcer. Research on HA for Recurrent Aphthous Stomatitis (RAS) has indicated good efficacy in pain alleviation and shortening healing time, typically without significant side effects.[21]
• Zinc:
• Immune Function Modulation: Zinc is an essential cofactor for numerous enzymes and transcription factors, playing a critical role in the normal development and function of cells mediating both innate and adaptive immunity.[2] Adequate zinc levels are necessary for maintaining the integrity of immune responses.
• Tissue Repair and Epithelial Integrity: Zinc is fundamentally involved in processes of cell proliferation, differentiation, and apoptosis, all ofwhich are crucial for wound healing and the maintenance of epithelial barrier integrity.[19] It contributes to collagen synthesis, re-epithelialization, and antioxidant defense mechanisms within tissues. Zinc supplementation has been investigated for various dermatological conditions and for recurrent oral ulcers, with some evidence suggesting benefits, particularly in individuals with suboptimal zinc status.[14]
• Relevance to Oral Aphthosis: The inclusion of zinc in the GV-328 lozenge aims to support local tissue repair mechanisms within the ulcer bed and potentially modulate the local immune response. While the GV-328 study did not focus on preventing recurrence, zinc's role in overall mucosal health could be beneficial.
• Combined Effect in GV-328 Lozenges: The formulation of GV-328 lozenges leverages the complementary actions of hyaluronic acid and zinc. The HA component primarily offers a physical barrier, symptomatic relief through protection and hydration, and direct promotion of the healing cascade. Simultaneously, zinc provides essential micronutrient support for the underlying cellular processes of tissue repair and local immune function. The slow-release lozenge formulation is key, as it ensures that both active ingredients are delivered directly to the site of the aphthous ulcer and maintained in contact with the oral mucosa for an extended period. This localized delivery is intended to maximize therapeutic benefit while minimizing systemic exposure and potential side effects. The combined approach addresses multiple facets of oral aphthous ulcer pathology: the physical breach in the mucosa, the associated pain and inflammation, and the biological processes required for healing.

5. Clinical Development and Efficacy: The NCT04677062 Study ("Safety, Galenic Acceptability and Efficacy of GV-328 Lozenges in Children With Oral Aphthosis")

The primary clinical evidence for GV-328 lozenges comes from the NCT04677062 study, conducted at the Universitat Internacional de Catalunya (UIC) and financed by Laboratorios Viñas.

• Study Design and Methodology:
• Trial Identification and Title: The study is registered under NCT04677062.[3] The official title in Spanish is "Estudio clínico de seguridad, aceptabilidad galénica y eficacia del preparado GV-328 en formato de pastillas para chupar en población infantil afecta de aftas bucales." This translates to "Clinical study of safety, galenic acceptability and efficacy of the GV-328 preparation in lozenge form in a pediatric population affected by oral aphthae".[1] It is also referred to by the English title: "Safety, Galenic Acceptability and Efficacy of GV-328 Lozenges in Children With Oral Aphthosis".[3]
• Sponsorship and Funding: The lead sponsor was the Universitat Internacional de Catalunya (UIC).[1] The study was financed by Laboratorios Viñas.[1] It is classified as an Investigator-Initiated Trial (IIT).[3]
• Study Type and Ethical Considerations: This was an open-label, prospective, non-controlled clinical study.[1] It received ethical approval from the Clinical Research Ethics Committee (ODP-ECL-2017-01) of UIC and was conducted in accordance with the principles of the Declaration of Helsinki.[1]
• Patient Population: The study enrolled 33 children, aged between 3 and 13 years, who presented with oral aphthae of a maximum 48-hour evolution. Exclusion criteria included the presence of multiple or traumatic lesions, concurrent use of other medications, and diabetes.[1]
• Intervention: Participants were treated with GV-328 lozenges. Each lozenge contained 5 mg of hyaluronic acid and 1 mg of zinc. The dosage was 4 to 6 lozenges per day, administered according to the child's age, for a duration of 4 days.[1]
• Outcome Measures: The primary efficacy and safety parameters included: pain intensity (assessed by both investigators and parents/patients using Likert scales), degree of functional limitation, edema of the marginal mucosa surrounding the ulcer, and changes in lesion size (categorized as <0.5 cm, 0.5-1.0 cm, or >1.0 cm). Healing time was also noted. Global judgments regarding efficacy, tolerability, acceptability, and ease of application were collected from both investigators and parents.[1]
• Study Duration and Procedures: The study involved an initial visit (Day 1) and a final visit (Day 5). Photographic documentation of the lesions was performed at both visits.[1]

Table 1: Summary of GV-328 Lozenge Clinical Trial (NCT04677062) Design and Key Parameters

• Efficacy Findings: The study reported positive outcomes across several efficacy measures 1:
• Pain Reduction:
• A statistically significant reduction in pain was observed daily by parent/patient assessment (p<0.01 or p<0.013). For instance, on Day 1, mean pain scores (scale not explicitly defined but contextually Likert-type) decreased from 4.3 before lozenge use to 3.6 after; Day 2: 3.2 to 2.6; Day 3: 2.4 to 1.9; Day 4: 1.4 to 1.0.
• Investigator assessment (0-5 Likert scale, 0=absent, 5=maximum) showed a mean pain score decrease from 4.3 (SD 0.7) at Day 1 to 0.7 (SD 1.0) at Day 5 (p<0.01).
• Notably, 100% of cases demonstrated an improvement in pain intensity. The consistent reporting of significant pain relief by both investigators and parents/patients strengthens the evidence for symptomatic benefit, a crucial outcome in managing a painful condition like pediatric oral aphthosis.
• Lesion Size Reduction:
• A statistically significant reduction in lesion size was observed from the initial visit to the final visit (p<0.01).
• By Day 5, 39% of participants (n=13) achieved complete healing of their aphthous ulcers.
• In the remaining 61% (n=20), the lesion diameter was less than 0.5 cm at the study's conclusion.
• Functional Limitation:
• Statistically significant improvements were noted in functional limitation (e.g., difficulty eating, speaking) (p<0.05 overall).
• Investigator assessment (0-5 Likert scale) indicated a decrease in the mean functional limitation score from 3.1 (SD 1.1) at Day 1 to 0.4 (SD 0.8) at Day 5 (p<0.01).
• Edema of Marginal Mucosa:
• A statistically significant reduction in edema surrounding the ulcer was observed (p<0.05 overall).
• Investigator assessment (0-5 Likert scale) showed the mean edema score decreasing from 2.6 (SD 1.0) at Day 1 to 0.6 (SD 0.9) at Day 5 (p<0.01).
• Healing Time: While not explicitly quantified as a primary endpoint, the data suggests a reduction in healing time compared to the typical spontaneous remission period for aphthous ulcers, which is generally 1 to 2 weeks.[22]

Table 2: Key Efficacy Outcomes of GV-328 Lozenges in Pediatric Oral Aphthosis (NCT04677062) - Investigator Assessment (0-5 Scale) [1]

• Investigator and Parent/Patient Global Assessments: Both investigators and parents provided positive global assessments regarding the efficacy, tolerability, acceptability, and ease of application of GV-328 lozenges, with ratings predominantly in the "good" or "excellent" categories. There were no statistically significant differences found between the assessments provided by investigators and those by parents for any of an evaluable variable.1 The principal limitation of this study is its open-label, non-controlled design. While the observed improvements from baseline are statistically significant, the absence of a placebo or active comparator group makes it challenging to definitively attribute the entirety of the observed benefits solely to GV-328, as opposed to the natural course of healing for aphthous ulcers or a placebo effect. Aphthous ulcers are known to heal spontaneously, typically within one to two weeks.[22] Therefore, the true magnitude of GV-328's specific therapeutic contribution cannot be unequivocally established from this study alone.

6. Safety and Tolerability Profile (from NCT04677062)

The NCT04677062 study also provided important data on the safety and tolerability of GV-328 lozenges in the pediatric population.

• Overall Safety: The product was reported to have a "good safety profile".[1] This is a critical aspect for any pediatric formulation, especially for a condition that, while painful, is generally self-limiting.
• Adverse Events:
• No serious adverse events (SAEs) were reported during the study.[1]
• The primary adverse event noted was nausea, which occurred in three participants (representing 9% of the 33 children enrolled). This nausea was reported at the beginning of the treatment and was attributed by the investigators to the taste of the product.[1] The mild and transient nature of this side effect suggests it did not significantly detract from the overall tolerability for most children.
• Galenic Acceptability:
• The galenic acceptability, referring to the physical characteristics and patient acceptance of the dosage form, was generally rated as good by both investigators and parents.[1]
• The lozenge formulation, designed for slow dissolution in the mouth and incorporating a plastic support to prevent premature swallowing, was specifically noted as facilitating topical application in children.[1] This design likely contributed to the positive acceptability ratings. The low incidence of only mild, taste-related adverse events is indicative of good general tolerability in children. This factor is paramount for ensuring compliance with oral treatments in this age group, where taste and ease of administration can significantly influence adherence to therapy.

Table 3: Safety and Tolerability Profile of GV-328 Lozenges from NCT04677062 [1]

7. Regulatory Status and Commercialization

The regulatory pathway and commercial availability of GV-328 are characteristic of a product positioned as a dietary or food supplement rather than a prescription pharmaceutical.

• Regulatory Classification:
• The Spanish clinical trial publication concerning NCT04677062 explicitly states that GV-328 is "currently commercialized as a dietary supplement".[1]
• Similarly, the product Oralchup, which aligns with GV-328's description, is referred to as a "food supplement" on the website of its manufacturer, Laboratorios Viñas.[2]
• This classification is significant because dietary or food supplements are not subjected to the same rigorous pre-market approval processes for efficacy and safety as medicinal products by regulatory authorities like the European Medicines Agency (EMA) or national drug agencies. The evidentiary standards for supplements primarily focus on safety for consumption and truthfulness in labeling, rather than proven therapeutic efficacy for specific medical conditions. This regulatory status influences how the product is marketed and the types of health claims that can be made.
• Manufacturer/Marketing:
• The clinical trial NCT04677062 was financed by Laboratorios Viñas.[1] Laboratorios Viñas is a pharmaceutical company based in Barcelona, Spain.[23]
• Brand Name: While "GV-328" appears to be the internal or investigational code used during research, the commercial product matching its description (lozenge with hyaluronic acid, zinc, and a plastic support for mouth sores) is marketed by Laboratorios Viñas under the brand name Oralchup.[2] The report establishes a clear link between the investigational GV-328 and the commercial product Oralchup based on compositional and formulation similarities and the involvement of Laboratorios Viñas.
• Availability:
• Oralchup is available in Spain, as indicated by its country of origin on an Amazon.be listing.[24]
• Laboratorios Viñas has a broader market presence, including East Asia, but specific details on the international availability of Oralchup are not extensively covered in the provided materials.[23]
• Patents:
• The provided information does not contain specific patent details for the exact GV-328/Oralchup formulation by Laboratorios Viñas. While general patents related to compositions containing hyaluronic acid and/or zinc for oral mucosal applications exist (e.g.[25] mentions patents for mineral salts and sulfonic acids for mucosal diseases, with classifications relevant to zinc and oral preparations), a direct link to a specific patent for this product is not established. One database notes "100 Patents (Medical) associated with GV-328" but lacks specifics.[3]

The decision by Laboratorios Viñas, a pharmaceutical entity, to market Oralchup as a food/dietary supplement while concurrently funding a clinical study (NCT04677062) is noteworthy. This approach may represent a strategy to substantiate the product's benefits with scientific data, thereby enhancing confidence among consumers and healthcare practitioners, without undertaking the more extensive and costly process of pharmaceutical drug registration. This is particularly relevant for products addressing common, often self-limiting conditions where consumers may seek gentler, readily accessible options.

8. Discussion

The investigation into GV-328 lozenges (commercially available as Oralchup) provides valuable insights into a non-pharmaceutical option for managing pediatric oral aphthosis.

• Summary of Key Findings: The NCT04677062 study, although open-label and non-controlled, demonstrated that GV-328 lozenges led to statistically significant improvements in primary symptoms of oral aphthosis in children. These include notable reductions in pain, lesion size, and functional limitations associated with the ulcers. The product also exhibited a good safety profile, with only minor, taste-related nausea reported in a small percentage of participants, and was well-accepted by the pediatric cohort.[1]
• Strengths of the Evidence: The study's prospective design, while lacking a control group, allowed for systematic data collection.1 The use of Likert scales for assessing subjective measures like pain, and the collection of assessments from both investigators and parents/patients, adds a layer of robustness to the symptomatic relief findings, particularly given the concordance between these assessments.1 The focus on a pediatric population addresses a clear need for child-friendly formulations. The lozenge design itself, with its slow-release mechanism and plastic support, is inherently suited for topical application in children, promoting prolonged contact time of the active ingredients with the oral mucosa.1
• Limitations of the Evidence: The most significant limitation is the study's open-label, non-controlled nature.1 Without a placebo or active comparator arm, it is difficult to definitively disentangle the observed effects of GV-328 from the natural healing trajectory of aphthous ulcers, which typically resolve spontaneously within 1-2 weeks 22, or from a potential placebo effect. The relatively small sample size of 33 children, while sufficient for an initial exploratory study, means that the findings should be interpreted with caution, and larger studies would be necessary for more definitive conclusions.4 The short follow-up period (treatment for 4 days, final assessment on Day 5) provides information on acute symptom relief but does not address the product's potential impact on the frequency of recurrence or longer-term mucosal health.1 Finally, the classification of GV-328/Oralchup as a dietary supplement means it is not subjected to the stringent evidentiary standards required for pharmaceutical drugs.
• Clinical Implications: GV-328 (Oralchup) can be considered a supportive, adjunctive option for children aged 3 years and older experiencing the discomfort of uncomplicated oral aphthous ulcers. Its favorable safety profile and formulation designed for pediatric use make it an appealing choice, particularly when parents or clinicians are seeking non-corticosteroid or non-anesthetic local treatments. Healthcare providers should, however, counsel caregivers about its status as a dietary supplement and the nature of the supporting clinical evidence. The primary utility, based on current data, appears to be symptomatic relief during acute episodes rather than a curative or preventative therapy for recurrent aphthous stomatitis.
• Comparison with Other Treatments (General Context): Standard management for aphthous ulcers can include topical corticosteroids to reduce inflammation, topical anesthetics for pain relief, and antiseptic mouthwashes to prevent secondary infection.13 GV-328 offers a distinct mechanistic approach by focusing on barrier formation (hyaluronic acid) and tissue support (zinc). The available research snippets do not include direct comparative studies of GV-328 against these other common treatments. The funding of the NCT04677062 study by Laboratorios Viñas for a product already marketed as a dietary supplement (Oralchup) likely serves a strategic purpose. It allows the company to generate and disseminate scientific data supporting the product's use, which can be valuable for marketing to healthcare professionals (such as pediatricians and dentists) and consumers, thereby lending a degree of scientific credibility to a non-prescription product.

9. Conclusion and Recommendations

• Overall Conclusion: GV-328 lozenges, identified as the commercial product Oralchup, contain hyaluronic acid and zinc and have been evaluated for the treatment of oral aphthosis in children. The NCT04677062 clinical trial, an open-label, prospective study, indicated that this formulation led to statistically significant improvements in pain, lesion size, and functional status in pediatric participants aged 3 to 13 years. The product was reported to be well-tolerated and demonstrated good acceptability within this age group, with no serious adverse events noted.[1]
• Recommendations for Use:
• GV-328/Oralchup may be considered as a non-prescription, supportive treatment option for children aged 3 years and older who are experiencing discomfort from simple, acute oral aphthous ulcers.
• Its primary role appears to be in providing symptomatic relief during these acute episodes.
• Caregivers should be advised to follow the recommended dosage (typically 4-6 lozenges per day, depending on age, for a duration of 4 days) and to note that it is not recommended for children under 3 years of age.[1]
• Given its status as a dietary/food supplement, expectations regarding its efficacy should be aligned with this classification, and it should not be viewed as a substitute for medical evaluation if symptoms are severe, persistent, or recurrent.
• Suggestions for Future Research:
• To more definitively establish the efficacy of GV-328/Oralchup, larger, randomized, placebo-controlled, and ideally active-controlled clinical trials are warranted. Such studies would help differentiate its effects from natural healing and placebo responses and compare its performance against existing treatments.
• Research into the potential of GV-328/Oralchup to prevent or reduce the frequency of recurrent aphthous ulcers could explore a broader utility for the product.
• Further investigation into optimizing the taste of the lozenge could help minimize even the mild, infrequent nausea reported, thereby enhancing its overall acceptability in the pediatric population.
• Comparative effectiveness studies against other commonly used topical treatments for pediatric oral aphthosis would provide valuable information for clinical decision-making.

The development and study of GV-328/Oralchup illustrate an increasingly common approach where products marketed as dietary or food supplements undergo clinical investigation. This strategy can provide a level of scientific support for their use, particularly for common, self-limiting conditions in sensitive populations like children, where safe and accessible options are highly valued. While the current evidence for GV-328 is promising for symptomatic relief, more rigorous research is needed to fully define its place in the management of pediatric oral aphthosis.

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