Graceway Pharmaceuticals Reports Study in New England Journal of Medicine: Aldara (imiquimod) Cream, 5% demonstrated a reduction in lesion size in patients with vulvar intraepithelial neoplasia

BRISTOL, Tenn.--(BUSINESS WIRE)--Apr 21, 2008 - A study published in the April 3, 2008 issue of The New England Journal of Medicine concludes that imiquimod cream, 5% (Aldara) "is a promising agent for the treatment of vulvar intraepithelial neoplasia." Vulvar intraepithelial neoplasia (VIN) is a pre-cancerous skin lesion of the vulva often caused by human papillomavirus (HPV). According to the authors, patients treated with Aldara did not experience certain side effects or limitations commonly associated with surgery, the most frequent treatment for VIN.

In a randomized study comparing imiquimod cream, 5% (Aldara) to placebo in 52 patients with grade 2 or 3 VIN lesions, a reduction in lesion size by more than 25% was demonstrated in 81% of patients treated with Aldara and in no patients treated with placebo at 20 weeks. (P less than .001). Lesions completely cleared in 34% of Aldara-treated patients and an additional 19% of patients experienced a reduction in lesion size greater than 75%. All 9 patients who were completely clear at 20 weeks remained clear at 12 months. Four of these 9 patients had 2 or 3 surgeries for VIN before being treated with Aldara.

About the Study

Aldara Cream or placebo cream was applied to lesions twice a week for 16 weeks. The primary endpoint was a reduction in lesion size of more than 25% 4 weeks after the end of treatment (20 weeks after the beginning of treatment). The secondary endpoints were histologic regression from grade 2 or 3 VIN to a lower grade, clearance of human papillomavirus (HPV), and changes in immune cells in the epidermis and dermis at 20 weeks; relief of clinical symptoms and improvement of quality of life at 20 weeks and at 12 months; and durability of clinical response at 12 months.

At 20 weeks, lesion size was reduced by more than 25% in 81% of patients treated with Aldara and in no patients in the placebo group (p less than .001). The lesions were eliminated in nine Aldara treated patients and were reduced by more than 75% in five. Patients who completely cleared remained free from disease at 12 months.

Histologic regression from grade 2 or 3 to a lower grade occurred in 69% of patients treated with Aldara and 4% of those treated with placebo (P less than .001). Complete histologic clearance was reported in 8 Aldara-treated patients. Histologic regression was strongly associated with viral clearance (P less than .001). HPV was completely cleared in 17 lesions, 15 after treatment with Aldara and 2 after treatment with placebo at 20 weeks.

Aldara-treated patients reported a significant reduction in itching and pain vs those treated with placebo at 20 weeks (P=.008 and P=.004, respectively) and at 12 months (P=.04 and P=.02, respectively). There was no significant difference between treatment groups on self-reported, health-related quality of life, body image, or sexuality at either time point.

The following side effects were reported significantly more frequently in Aldara treated patients: vulvar pain or itching, apathy, mild to moderate redness and skin erosion, severe redness and swelling. One Aldara-treated patient and two placebo-treated patients developed invasive VIN during the follow-up period.

Aldara is an immune-response modifier. In this study, patients who had lesion regression greater than 75% demonstrated a significant increase in the number of dendritic cells, T cells and natural killer cells in the epidermis at 20 weeks. The investigators state that "the increase in the number of immune cells in the epidermis of patients with a clinical response of more than 75% after imiquimod treatment may reflect reactivation of the resident epidermal cells."

About Vulvar Intraepithelial Neoplasia (VIN)

VIN is a preinvasive squamous cell carcinoma (carcinoma in situ) similar to cervical intraepithelial neoplasia (CIN) or dysplasia. VIN is caused by HPV infection. Surgical removal of lesions is the treatment of choice, but has limitations, including poorly defined surgical margins, disfigurement of the vulva, and recurrence because surgery does not remove HPV.

About ALDARA

Aldara Cream is not FDA-approved for the treatment of VIN.

ALDARA is the brand name for imiquimod, which is an immune-response modifier. Aldara Cream is a skin-use only (topical) medicine used to treat external genital and perianal warts/condyloma acuminata in patients 12 years old or older.

Safety and efficacy of ALDARA Cream in immunosuppressed patients have not been established. The most common side effects are application site reactions or local skin reactions: itching, burning, redness, flaking/scaling/dryness, scabbing/crusting, edema, peeling, skin that becomes hard or thickened, erosion, and ulceration. Most skin reactions are mild to moderate in nature. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in practice. The effect of Aldara Cream on the transmission of external genital warts is unknown. Aldara Cream may weaken condoms and diaphragms. Sexual contact should be avoided while the cream is on the skin. New external genital warts may develop during treatment.

About Graceway Pharmaceuticals, LLC

Graceway Pharmaceuticals, LLC ("Graceway"), headquartered in Bristol, TN, is a pharmaceutical company focused on acquiring, in-licensing, and developing branded prescription pharmaceutical products. Current prescription products marketed by Graceway include ALDARA(R) (imiquimod) Cream, 5%, Maxair(R) Autohaler(R) (pirbuterol acetate inhalation aerosol), Atopiclair(R) Nonsteroidal Cream, and Estrasorb(R) (estradiol topical emulsion). ALDARA(R), Maxair(R), Autohaler(R), Atopiclair(R), and Estrasorb(R) are trademarks owned by or licensed to Graceway. For more information on Graceway's products, including important safety information, please visit www.gracewaypharma.com.

Reference: van Seters M, van Beurden M, ten Kate FJW, Beckmann I, Ewing PC, Eijkemans MJC, et al. Treatment of vulvar intraepithelial neoplasia with topical imiquimod. N Engl J Med. 2008;358(14):1465-1473.

Contact

Graceway Pharmaceuticals, LLC
Jim Lee, MD, PhD
Chief Medical Officer
1-800-328-0255

Posted: April 2008

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