News today that Sol-Gel Technologies has filed for Investigational New Drug for a product they are calling DED45-EV. This topical gel is targeted as a treatment for rosacea.

There doesn’t seem to be other copies of this release, or related information so this could just be a pure PR exercise.

The exact details of the active ingredients in this product are not being made public. So far, only PR speak along the lines of ““As Sol-Gel’s microcapsulation forms a protective barrier between the drug and the skin, we expect it to reduce irritation when applied to the relatively sensitive skin of rosacea patients,“said Dr. Stanley Shapiro, Sol-Gel’s Head of Skin Care Science & Technology.” is being published.

My guess back in July in Sol-Gel Trialling Benzoyl Peroxide (DER 45 EV) for Rosacea ? was that this topical gel was in fact benzoyl peroxide. Certainly the publicity so far from Sol-Gel has been related to acne and acne treatments.

Sol-Gel Anti-Acne Clinical Study Shows Significantly Improved Efficacy and Safety

“In the Sol-Gel kits, the proprietary silica microcapsules encase and continuously release the benzoyl peroxide, enabling a significant increase in efficacy and tolerance in comparison to products containing free benzoyl peroxide

As I said in July, many rosacea sufferers will know from their own experiences, many acne treatments are just too harsh for their sensitive rosacea skin.

If anyone sees some more information that confirms the makeup of DER45-EV please do let us know.

Related Articles

• Business Wire: Sol-Gel’s IND Application for Rosacea Accepted by FDA
• Sol-Gel Trialling Benzoyl Peroxide (DER 45 EV) for Rosacea ?

WARNING LETTER

The FDA has reviewed a journal advertisement (APC021052008) for ACZONE® (dapsone) Gel, 5% (ACZONE) (and) this journal advertisement is false or misleading because it grossly overstates the efficacy of ACZONE, and omits material facts and important risk information associated with the use of the product.

The offending advertising claims.

The journal article overstates the effectiveness of Aczone by neglecting to state that at 2 weeks usage, Aczone was only 2% more effective than the placebo vehicle gel. This small difference is not considered statistically significant so it not a true claim of efficacy. The 12 week trial results were also over stated by ignoring the comparative effect of the vehicle gel.

The second part of the warning deals with the omission of important risk information associated with Aczone. Clinical trials found that 7 out of 95 subjects who applied benzoyl peroxide after applying Aczone had yellow or orange discoloration of the skin and facial hair. This discoloration took between 4 and 57 days to resolve.

The FDA attracts a lot of criticism from rosacea sufferers who see the organisation as overly bureaucratic and unnecessarily slowing down new drug applications. We do need a policeman to help protect us from cynical vendors who make claims that are not based on proven facts. Personally I’m glad that the FDA is willing to publicise vendors who try to take advantage of rosacea sufferers.

An important message here is that rosacea sufferers would be wise to be wary of statistical claims in advertising materials. Seek out published proof before believe what you read.

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• cutanix goes offline, gets letter from FDA
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Clinical Trial NCT00940992, A Dose-Range of DER 45-EV in Treatment of Rosacea (SGT-EBPO1-09)

To identify lowest efficacious dose of DER 45 EV Gel, 1% and 5% verses vehicle in patients with rosacea.

DER 45 EV Gel, 1%: Experimental, vs. Placebo Gel applied topically once a day for 12 weeks, vs. DER 45 EV Gel, 5% applied topically once a day for 12 weeks.

It isn’t clear if DER 45 EV is in fact benzoyl peroxide, this is just a guess based on the technologies being promoted by the company sponsoring this trial, Sol-Gel. The company’s technology is to use silica based microcapsules (cutely named Cool Pearls) that will allow a continual release of the active ingredient. Their Anti-Acne kit consists of a cleanser, toner, lotion and also spot treatment.

Sol-Gel Anti-Acne Clinical Study Shows Significantly Improved Efficacy and Safety

The results demonstrate that the company’s two strength Anti-Acne kits achieved pronounced efficacy and markedly improved tolerability.

…

“In the Sol-Gel kits, the proprietary silica microcapsules encase and continuously release the benzoyl peroxide, enabling a significant increase in efficacy and tolerance in comparison to products containing free benzoyl peroxide,”

The marketing material for Sol-Gel Technologies gives the following description of the process behind creating their products – “Silicate materials are made by forming interconnections among colloidal nano-sized particles (the sol) under increasing viscosity, until a rigid mass is formed with about half the density of glass (the gel). Sol-Gel precisely engineers the process to fine-tune the size, structure and properties of the materials formed. The resulting drug delivery properties range from completely non-leachable to a selectively porous barrier that allows controlled release of active ingredients after the product is applied to the skin.”

The trial is listed to start in January 2010 so perhaps we will be able to find out more information before then.

This is a potentially interesting development, especially if this means that a harsh treatments such as benzoyl peroxide is tolerable by and beneficial to rosacea sufferers.

As many rosacea sufferers will know from their own experiences, many acne treatments are just too harsh for their sensitive rosacea skin.

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• Medicis readies to trial Ziana for rosacea
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Just posted on the clinicaltrials.gov database is an entry “Safety and Efficacy Study of Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel to Treat Rosacea”. This topical product, known as Ziana, is currently approved for the treatment of acne.

Ziana is manufactured by Medicis who also make Plexion and Solodyn. The combination of tretinoin and clindamycin may be too harsh for some rosacea sufferers, so it will be interesting to see how the trial pans out. Ziana is marketed as the only topical to combine an antibiotic and a retinoid.

The trial will primarily measure a reduction in the count of papules and pustules from baseline to week 12. A secondary measurement will be transient redness. We can deduce from this that Ziana is only thought to be effective against the inflammatory lesions of rosacea, and will likely only have a mild effect on the redness.

Rosacea sufferers have many choices to treat papules and pustules, so sufferers may well be left wondering, why one more ? If you can’t tolerate metrogel, metrolotion, metrocream, noritate, topical clindamycin, finacea or plexion (just to name a few), then maybe, at a stretch, Ziana might offer you another viable option.

Have you tried Ziana for your rosacea ? How did you find it ?

Related Articles

• RSRP: Solodyn, Plexion
• rosacea-support message 97926 on Ziana

A question we hear from time to time from rosacea sufferers is `how do I go about reducing the size of my skin pores ?’ This is quite a difficult question to properly answer. The enlarged pores that you sometimes see with rosacea or acne can feel like they will never go away.

You are here on this page because you feel sure that there must be a way to reduce the inflammation that leads to swollen pores on your face.

Here are some insightful thoughts from Dr. Linda Sy;

Pores can appear enlarged if filled with sebum & keratinized cells. When the epithelial cells are exfoliated or the sebum production is inhibited (example: by topical tretinoin or accutane prescription), the pores appear smaller. Therefore, any prescription that will reduce accumulation of sebum & keratin in the pores, will most likely help reduce the size.

I doubt that many doctors would recommend that you undertake a treatment regime of accutane just to reduce visible facial pores. If you also have the lump and bumps of acne, or severe pustules and redness of rosacea, you may find accutane is helpful in reducing the pore size also.

The NRS Ask the Doctors Blog also has a post asking Rosacea has made the pores on my face large. When I get my rosacea under control, will my pores return to their normal size?

The Rosacea Experts also come to a similar conclusion as Dr. Sy;

Topical and oral antibiotic therapy may be prescribed for mild cases, but more severe cases may sometimes be treated with isotretinoin, which is an oral medication typically used for severe acne. Clinical studies have shown that patients’ large sebaceous glands were diminished in size and number during isotretinoin therapy. There is also evidence that retinoids, topical medications with many of the same properties of isotretinoin, may decrease skin thickening and sebaceous gland enlargement. Spironolactone, a mild diuretic with anti-androgen properties, can also be used to decrease pore size.

Good to see some more suggested treatments for enlarged pores as I know this is something that worries many rosacea sufferers.

Featured Product

Over To You

Please leave a comment below with any hints or tips you have found that have helped you answer the question “how do I reduce the size of my pores ?”

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• Low Dose Accutane

From: Allergan Announces Agreement to Acquire Aczone(R) Gel 5%

“Aczone(R) Gel 5% is the first new chemical entity approved by the FDA for the treatment of acne in several years, and represents an important clinical advance in dermatology with a robust safety and efficacy profile demonstrated in more than 3,000 patients,” said Scott Whitcup, M.D., Allergan’s Executive Vice President of Research and Development. “We are excited to make Aczone(R) Gel 5% widely available to dermatologists and their patients in North America, underscoring our commitment to continue to invest and respond to unmet medical needs in dermatologic therapies and building upon our more than 10 years of success with TAZORAC(R).”

Aczone is 5% topical dapsone gel. Originally targeted as an acne treatment, it has also been trialled as a rosacea treatment. Aczone is contraindicated for anyone with a history of anemia or an enzyme deficiency.

The new owners of Aczone are Allergan who perhaps are better known for making the dry eye treatment Restasis, Refresh artificial tears, and the product that was the genesis of Sansrosa – Alphagan P.

I am yet to see any results from the trials for treating rosacea with Aczone. It will be interesting to see if Allergan has plans to broaden the marketing of Aczone to include rosacea.

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• aczone (topical dapsone) recruiting trial participants
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This poster session is seeking to expand the appeal of Finacea (which contains Azelaic acid 15%) beyond rosacea. The result is that the authors are suggesting that finacea is also possibly good for acne vulgaris and hyperpigmentation as well as rosacea. If you are interested in reading more about rosacea, and its applicability to rosacea, see my previous article focus on finacea.

P433 Implications of azelaic acid’s multiple mechanisms of action: Therapeutic versatility, Zoe Draelos, MD, Allan Kayne, MD, Intendis, Inc.,

Poster Abstracts, American Academy of Dermatology 66th Annual Meeting, February 1–5, 2008, San Antonio, Texas. Supplement to the JAAD, Feb 2008, Volume 58, Number 2.

Introduction: Topical azelaic acid (AzA) 15% gel is approved in the United States for the treatment of mild to moderate papulopustular rosacea and shows efficacy against erythema in the presence of inflammatory lesions. However, the multiple mechanisms of action of AzA make it a candidate for use in other dermatoses.

Objective: To understand the benefits of the various mechanisms of action of AzA in dermatologic disorders other than rosacea. AzA demonstrates both anti-inflammatory and antioxidant effects on rosacea. [1] Patients with rosacea have defects in stratum corneum (SC) barrier function. [2] In a previous study, 40 women using AzA had no increase in transepidermal water loss from the SC versus controls. [3] Data from a recent in vitro study has demonstrated bacteriostatic effects of AzA on P acnes. [4] AzA is also a competitive inhibitor of tyrosinase [5] and has cytotoxic effects on hyperactive melanocytes. [6] The antiinflammatory, antioxidant, antikeratinizing, and bacteriostatic properties of AzA make it an excellent therapeutic option in acne vulgaris. [5,6] By inhibiting tyrosinase, AzA interferes with the production of excessive melanin and also has direct cytotoxic effects on the hyperactive melanocytes seen in people with hyperpigmentation disorders. [5,6]

Conclusion: The multiple mechanisms of action of AzA suggest it has utility in dermatologic conditions beyond rosacea.

References:

1. Akamatsu H, Komura J, Asada Y, et al. Inhibitory effect of azelaic acid on neutrophil functions: a possible cause for its efficacy in treating pathogenetically unrelated diseases. Arch Dermatol Res 1991;283:162-6.
2. Dirschka T, Tronnier H, Fo¨lster-Holst R. Epithelial barrier function and atopic diathesis in rosacea and perioral dermatitis. Br J Dermatol 2004;150:1136-41.
3. Draelos ZD. Noxious sensory perceptions in patients with mild to moderate rosacea treated with azelaic acid 15% gel. Cutis 2004;74:257-60.
4. Data on file, Intendis, Inc.
5. Fitton A, Goa KL. Azelaic acid: a review of its pharmacological properties and therapeutic efficacy in acne and hyperpigmentary skin disorders. Drugs 1991;41:780-98.
6. Nguyen QH, Bui TP. Azelaic acid: pharmacologic and pharmacodynamic properties and its therapeutic role in hyperpigmentary disorders and acne. Int J Dermatol 1995;34:75-84. 100% is sponsored by Intendis, Inc.

Related Articles

• Rosacea News finacea articles section
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An interesting blog posting over at Baby Toolkit suggests that 10% benzyl peroxide cream and sunlight is perfect for removing pen marks from a plastic doll.

From Clear Unsightly Blemishes: the Case of the Ballpoint Baby Doll

Here is before ;

and here is after

The post ends with "Moral of the story? Don’t leave pens unattended around toddlers -or- be very cautious about wearing acne cream in direct sunlight".

That benzyl peroxide is powerful stuff. No wonder it drives most rosacea sufferers crazy !

Background: Zileuton, a 5-lipoxygenase inhibitor, reduces the number of inflammatory lesions in moderate acne and inhibits the synthesis of sebaceous lipids. Objective: To detect whether zileuton directly reduces sebum synthesis.

Methods: A 40-year-old female with mild disseminated sebaceous gland hyperplasia and seborrhea was treated with zileuton 4 x 600 mg/day over 2 weeks, was followed-up for 6 weeks after discontinuation of zileuton and was re-treated with low-dose isotretinoin 10 mg/2nd day over 5 weeks. Casual skin surface lipids and sebum synthesis were determined.

Results: Under treatment with zileuton increased casual skin surface lipids were normalized and synthesis of facial sebum was decreased. Six weeks after discontinuation of treatment casual skin surface lipids were increased again and synthesis of sebum returned to baseline. Subsequent low-dose isotretinoin treatment led to similar changes of casual skin surface lipids and sebum synthesis with zileuton already after 2 weeks.

Conclusion: Zileuton directly inhibits sebum synthesis in a transient manner with a potency similar to low-dose isotretinoin at least in our patient.

• PubMed Abstract

 

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Rambazole is still in development, having recently reported results in Phase 2a trials for the oral formulation for moderate to severe acne and measuring biological activity for the topical formulation. Their aim is to develop an oral formulation of Rambazole for the treatment of psoriasis and severe acne, as well as a topical formulation for psoriasis, acne, and wrinkles.

From Barrier Therapeutics Development Pipeline

Rambazole is our second product candidate based on the RAMBA class of molecules. We are developing an oral formulation of Rambazole for the treatment of psoriasis and severe acne and a topical formulation for dermatological indications, including common forms of acne and mild to moderate psoriasis. Preclinical studies suggest that Rambazole is more selective and more active than first generation RAMBA-based product candidates, such as Liarozole.

Oral Rambazole – We are currently conducting two Phase 2a clinical trials using oral Rambazole, one in moderate to severe psoriasis and the other in moderate to severe nodular acne. A review of initial Phase 2a trial data from 10 patients with moderate to severe psoriasis demonstrated a reduction in the psoriasis area severity index, commonly known as PASI score, by an average of 50% in patients treated with 1 mg once daily for eight consecutive weeks. These PASI scores were measured at week 10, two weeks after stopping the treatment. Based on these data in mid-2005, we plan to submit an IND or its European equivalent necessary for us to commence Phase 2b clinical trials of oral Rambazole for psoriasis.

Further Reading:

• oral rambazole and psoriasis: phase IIA study from AAD Poster
• rambazole dose and side effects being studied