Science

Background

Oral leukoplakia is a potentially cancerous white patch or plaque in the mouth, strongly linked to smoking. The edges of the lesion are typically abrupt and the lesion changes. Oral leukoplakia also has dysplasia which highlights the severity of the disorder and is a marker of disease progression. Dysplasia is abnormal cell growth, a precancerous condition more serious than normal cell overgrowth (hyperplasia). In adults, precancerous dysplasia may not always turn into cancer, but there's a risk it could.

Key Statistics/Information on Oral Leukoplakia

Based on prevalence estimates of 2% of the general population there are an 15M leukoplakia patients in the US (6.6M) and EU (8.9M) combined. Approximately 80% of leukoplakia lesions occur in the oral cavity and could be treated by a patch (as determined by market research). Cancers of the oral cavity (lip, oral tongue, gingiva, floor of mouth, palate, and other mouth, including buccal mucosa) account for approximately 250 000 annual incident cases. Incidence of oral cancer was substantially elevated in patients with oral leukoplakia), including enormously high risk in the first year following a leukoplakia diagnosis.

Market / Statistics

The global market for oncology drugs was estimated at USD 135 billion in 2020 and is expected to reach USD 274 billion in 2030, registering a CAGR of 7.5% from 2021 to 2030.

Size Industry

Based on statistics from Market Research Future the market size for oral cancer treatment were valued at approx. USD 2.0 billion in 2023 and is expected to reach approx. USD 2.74 billion in 2030, registering a CAGR of 5.40% from 2023-2030. Increased prevalence of oral cancer is one factor that is attributing to the market boost for oral cancer treatment going forward.

Scientific Findings

Incidence of oral cancer was substantially elevated in patients with oral leukoplakia. Individuals with oral leukoplakia bear a substantially elevated risk of oral cancer, with enormously high risk within 1 year of a precancer and notably elevated risk beyond 1 year. Risk of progression to oral cancer was elevated for all grades. The 5-year competing risk–adjusted absolute risk of oral cancer in patients with oral leukoplakia was 3.3% absolute risks were higher for leucoplakias that were biopsied compared with leucoplakias that were not biopsied. Treatment recommendations depend on features of the lesion. follow up at three-to-six-month intervals may be sufficient. The percentage of people affected is estimated at 1–3%. Leukoplakia becomes more common with age, typically not occurring until after 30 Rates may be as high as 8% in men over the age of 70. with time.

Histological features connect to cancer and survival

Mild Dysplasia

Slight nuclear abnormalities, most marked in the basal third of the epithelial thickness and minimal in the upper layers, where the cells show maturation and stratification
A few abnormalities, but no abnormal mitoses may be present, usually accompanied by keratosis and chronic inflammation.

Moderate Dysplasia

More marked nuclear abnormalities and nucleoli tend to be present with changes most marked in the basal two-third of the epithelium, nuclear abnormalities may persist up to the surface, but cell maturation and stratification are evident in the upper layers
Mitoses are present in the parabasal and intermediate layers, but none is abnormal.

Severe Dysplasia

Marked nuclear abnormalities and loss of maturation involve more than two-third of the epithelium with some stratification of the most superficial layers
Mitoses some of which are abnormal may be present in the upper layers

Leukoplakia patients with dysplasia are at increased risk of recurrence and malignant progression

Based on prevalence estimates of 2% of the general population there are an 15M leukoplakia patients in the US (6.6M) and EU (8.9M) combined.
Approximately 80% of leukoplakia lesions occur in the oral cavity and could be treated by a patch (as determined by market research.
Dysplastic lesions are present in 20% of cases and represent a high-risk patient population. These patients are treated surgically today, but have a high risk of progression and recurrence
- 3–7x increased risk of progression to squamous cell carcinoma
- 30% progress to oral cancer within 10 years
Physicians readily identify patient characteristics for which a pharmacological treatment is likely to be preferred based on the following characteristic.

Leukoplakia can present throughout the oral cavity, with the shape and edge definition linked to cancer risk

It is estimated that about 80% of leukoplakia occurs in the oral cavity, with the remainder in the throat or larynx.

60% present as homogeneous oral leukoplakia (A)

Flat and uniform plaque with a smooth surface and well-defined margins 20 – 30% of homogeneous lesions will become cancerous.

40% present as non-homogeneous oral leukoplakia (B)

Also called proliferative leukoplakia, white plaque and areas of erythema accompanied by areas that contain nodules and/or verrucous parts with ill-defined margins 50 – 60% of non-homogenous will become cancerous.

Risk of progression to oral cancer statistically significantly increased with the grade of dysplasia. Most oral cancers have a premalignant lesion stage. Regular monitoring for progression of premalignant lesions is critical for the early detection and treatment of oral cancer. Oral leukoplakia, the most common potentially cancerous oral lesion, progresses to squamous cell carcinoma

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Physicians and payers aligned on dysplastic patients not recommended for surgery as the most relevant population, with possible expansion later

Patients not recommended for surgery serve as the point of entry. The trial design and payer support for these patients is more straightforward, especially for EU payers.
Then, life cycle management can expand into patients with any kind of dysplastic lesions, as leukoplakia KOLs noted that (if efficacious) they would be interested in using in a wider population. There may be a lower rate of recurrence with a pharmacological option as compared to excision.

Patient Characteristic

Patients with leukoplakia in the oral cavity:
- - Lesions on the gingiva, tongue, buccal mucosa and palate, are accessible regions where the patch can adhere

Patients with confirmed diagnosis of leukoplakia with dysplasia

- - All levels of dysplasia, but not cancerous as that requires more immediate excision or cancer therapies
  - Oral medicine specialists noted the importance of a biopsy to exclude patients with keratosis or scarring that may look like leukoplakia

Patients not recommended for surgery or excision

- Non-homogenous lesions: Due to their proliferative nature, these lesions are not well defined and often cover broad areas, making excision extremely difficult or impossible
- Sensitive locations: Excision from areas such as the tongue risk loss of oral function, potentially hindering a patient’s ability to eat and talk.

Additionally, patients should be undergoing cancer-related lifestyle adjustments, such as cessation of tobacco

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Oral leukoplakia (OL) has a malignant transformation rate, which means that it can develop into oral cancer over time.

Total prevalence of 1.39%. (up to 2,66)

The average rate of malignant transformation of OL is 13%.

One of the most important factors that affects the malignant transformation rate of OL is the presence and degree of epithelial dysplasia, which is a microscopic sign of abnormal cell growth and differentiation. Epithelial dysplasia can be classified into low-risk or high-risk dysplasia according to a new binary system proposed by the World Health Organization (WHO).

Low-risk dysplasia includes mild and moderate dysplasia, while high-risk dysplasia includes severe dysplasia and carcinoma in situ.

High-risk dysplastic OL has a significantly higher risk of malignant transformation than low-risk dysplastic OL.

A retrospective cohort study with OL found that high-risk dysplastic OL had a 4.57-fold increased risk of malignant transformation compared with low-risk dysplastic OL

Oral cancer incidence was substantially elevated in oral leukoplakia patients.

Cancers of the oral cavity (lip, oral tongue, gingiva, floor of mouth, palate, and other mouth, including buccal mucosa) account for approximately 250 000 annual incident cases. Incidence of oral cancer was substantially elevated in patients with oral leukoplakia), including enormously high risk in the first year following a leukoplakia diagnosis.

Defined clinically based on visual examination (a white patch in the mouth), erythroplakia (a red patch in the mouth), and oral submucous fibrosis (irreversible fibrosis of the submucous tissue) as well as histopathologically based on the presence of dysplasia.

The natural history of oral leukoplakia, the most common oral precancerous lesion, remains poorly characterized. The rate of progression of oral leukoplakia to invasive oral cancer are poorly defined.