What’s New in Dermatology Drugs?
Besides psoriasis, drugs such as Amevive and Raptiva, suggests Dr. Leonardi, may find a place in treating other chronic inflammatory disorders, such as atopic dermatitis. Once the drugs are used for psoriasis, you’re likely to see them used elsewhere, and chronic eczema will be one of the first paces.As mentioned earlier, in atopic dermatitis the topical immunosuppressants Protopic from Fujisawa and pimecrolimus (Elidel) from Novartis provide new treatment options.
These agents are already “making a dramatic change,” says Dr. Kess. They work extremely well as maintenance therapies, he says, after initial treatment with topical steroids.
Emmanuel Loucas, M.D.,Advanced Dermatology P.C. and The Center for Laser and Cosmetic Surgery Manhattan and Long Island, NY, looks for these two drugs to be used in multiple skin conditions. They include alopecia areata, graft versus host disease, lichen planus, pyoderma gangrenosum, sarcoidosis and vitiligo.
ACNE AND ROSACEA
Unlike psoriasis, no new blockbuster treatments promise treatment of acne in the near term. But treatments for rosacea are another story.
Azelaic acid gel 15% (Finacea) was approved early this month for the treatment of the inflammatory papules and pustules caused by mild to moderate rosacea. Finacea is the first new therapy for rosacea in more than a decade. Berlex will launch its drug in the first quarter of this year.
A study for a systemic treatment for rosacea is also underway. Last summer, CollaGenex Pharmaceuticals began Phase III clinical trials with its doxycycline hyclate tablets, 20 mg. (Periostat). Galderma also launched a daily cleanser, sodium sulfacetamide 10%, sulfur 5% (Rosanil), which is meant to complement topical rosacea therapy.
For acne, advances involve the way medications are combined, says Dr. Feldman. Recognition is growing, he says, that topical retinoids can help not only comedones but also inflammatory lesions. Clinicians may use retinoids with topical and oral antibiotics to treat different types of acne.
Allergan’s oral tazarotene (Tazorac) offers a shorter half-life compared to Roche’s isotretinoin (Accutane), says Dr. Leonardi. Because of concerns about pregnancy and possibly depression when administering retinoids, any drug that works in the same fashion but offers a shorter half-life would represent an advance, he says.
In addition, Stiefel Labs just launched its new product to treat inflammatory acne. Clindamyicin, 1% benzoyl peroxide, 5% (Duac Topical Gel) is approved for once-a-day dosing.
Currently, trials are underway on topical dapsone gel, says Dr.Weinberg, also assistant clinical professor of dermatology at Columbia University College of Physicians and Surgeons, New York. Anecdotal evidence indicates that the antibiotic has an effect.
Photodynamic therapy (PDT) is another area that holds promise. It involves administering a topical photosensitizing agent and then subjecting the area to a blue light. Doing so causes the release of free oxygen radicals, which can destroy the organism Propionibacterium acnes. Some methods involve high intensity blue light without the photosensitizing agent.
Already approved for genital warts, 3M’s topical immunomodulator imiquimod (Aldara) cream 5% is the most exciting treatment for actinic keratoses, says Dr. Weinberg.
Phase III trials are nearing completion, and researchers are studying several dose regimens, he says. (The literature also indicates that the drug is successful for nodular and superficial basal cell carcinoma and Bowen’s disease, he says.) Diclofenac sodium (Solaraze gel 3%) from Bioglan Pharma, Inc. is another effective approach. In theory, this NSAID inhibits the cyclooxygenase pathway, which leads to decreased prostaglandin synthesis.
One benefit of this therapy is that patient compliance tends to be better, says Dr. Loucas. It’s much less irritating than traditional fluorouracilmedications. That means patients are more likely to apply Solaraze gel for longer periods of time. Recently approved by the FDA. Solarze represents a “nice breakthrough,” he says.
Carac (Dermik Laboratories), a diluted form of 5-fluorouracil, can also be of benefit. Clinicians are also using PDT for actinic keratoses.
Clinicians are also studying Aldara to treat skin cancers, particularly basal cell carcinoma, says Dr. Loucas. Several studies, he says, showed complete resolution of skin cancer after 12 to 20 weeks of treatment.
Extending the PDT trand, Novartis Ophthalmics and QLT Inc. have announced the start of patient enrollment in two Phase III clinical trials using PDT with verteporfin for the treatment of multiple basal cell carcinomas.
A Phase II trial demonstrated preliminary safety and efficacy of verteporfin at three light doses in patients with non-melanoma skin cancer with multiple lesions.
The group of patients that was exposed to the highest light dose had the best response rate. In this group, 98% of the assessed tumors showed a complete clinical response following 6 months of initial treatment.
For melanoma, current research focuses on vaccines to help broaden the immune attack against the disease. Researchers are looking at three ways to deliver antigen genes to the patient; into the blood using plasmid DNA; retrovirus; and adenovirus, says Dr. Loucas. Immunization, he notes, will likely require a combination of the three delivery systems.
Future development of vaccines, says Dr. Weinberg, may offer a better alternative than interferon or interleukin as adjuvant therapy for advanced disease.
MORE POTENTIAL ADVANCES
Besides drugs for these major conditions, other agents hold out hope for dermatology patients:
- Thalidomide for pyoderma gangrenosum and refractory aphthous ulcers in the mouth.
- Resiquimod (3M), a relative of imiquimod, for genital herpes.
- In addition, although it’s not new, hydrocortisone buteprate 0.1% (Pandel) for psoriasis and atopic dermatitis will be relaunched in 2003 by CollaGenex.
GENE THERAPY FOR THE FUTURE
Though biologic therapies and other advances are likely to transform dermatologists’ prescribing patterns in the near term, gene therapy holds the promise for long-range changes. Right now, gene therapy is in the “infant stage,” says Dr. Lebowohl. Genetics is “always just over the horizon,” says Datamonitor’s Mr. Pang.
While some rare genetic defects produce skin diseases, most dermatology conditions are multlifactorial, says Joseph Fowler, Jr., M.D., clinical professor of dermatology at the University of Louisville. That means genetic therapy may be most beneficial, he says, for a small group of patients with those genetic diseases.
Drugs in development today may have far-reaching effects in other areas. “The dermatology market,” says the Datamonitor report, “represents an effective route to other autoimmune diseases. Dermatological disorders provide a prototypic model for other autoimmune diseases, in terms of disease pathogenesis, and serve as an ideal proof-of-concept model since drug effectiveness can be easily assessed via changes in skin appearance. This will greatly increase the market potential for new biologics in development for the treatment of dermatological disorders.”