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Investigational Topical Minocycline Gel for Acne Advances to Phase III Development

Results of the the Phase 2b OPAL study for BPX-01 in the treatment of Acne

Ted Lain, MD

Ted Lain, MD's avatar

Published online: May 25, 2017

Disclosures of potential conflicts of interest and author contributions are found at the end of this article.

BACKGROUND: Clinical trial investigator Dr. Ted Lain comments on the results of the OPAL study, a Phase 2b clinical trial which evaluated the efficacy of a novel topical gel formulation of the antibiotic minocycline (BPX-01) in reducing the number of inflammatory lesions in patients with moderate-to-severe inflammatory, non-nodular acne.

Acne may be viewed as a teenage affliction, but reality suggests something far different. More than 50% of people over the age of 25 still deal with some degree of acne.[1] It’s the most common skin condition in the U.S., and although it is more prevalent in adolescents, studies have shown an increase in adult acne with people receiving treatment well into their mid-40s.[2,3]

The root causes of acne are difficult to pinpoint, but stem from a number of internal and external factors, including hormonal imbalances, diet and stress. Biologic and environmental conditions lead to the blockage of hair follicles with bacteria, oil and dead skin cells resulting in chronic skin inflammation.[4,5] Acne can manifest in different ways and consists of both inflammatory and non-inflammatory lesions on the face, neck, chest, back and shoulders. In addition to these physical symptoms, acne can cause emotional distress such as poor self-image, depression and anxiety.

I recently served as an investigator for a Phase 2b clinical trial studying a novel topical gel formulation of the antibiotic minocycline (BPX-01) in patients with moderate-to-severe acne that may lend promise to a new treatment strategy for this far-reaching condition. BPX-01 is an investigational delivery system that formulates the leading acne antibiotic, minocycline, into a unique, hydrophilic topical gel.

The Phase 2b OPAL study was a randomized, double-blind, three-arm, vehicle-controlled dose-finding study. It enrolled 226 subjects (9 to 40 years old) with moderate-to-severe inflammatory, non-nodular acne. Topline results showed that the study met its primary endpoint with statistical significance, demonstrating that both 1% and 2% doses of BPX-01 significantly reduced the number of inflammatory acne lesions when compared to vehicle after 12 weeks of treatment. The absolute mean change in the number of inflammatory lesions from baseline was -15.4 lesions with the 2% dose (p=0.022 compared to vehicle) and -15.5 lesions with the 1% solution (p=0.037 compared to vehicle). The vehicle demonstrated a reduction of -11.3 lesions compared to baseline.

In a clinical trial setting, lesion counts provide a quantitative method to assess treatments and evaluate the severity of a person’s acne. But in a real-world setting, in-office evaluations tend to be more qualitative and assessed by a visual inspection. This is why the FDA offers guidance to include an additional qualitative measure, called Investigator’s Global Assessment (IGA), as a primary endpoint measure for acne severity in Phase 3 clinical trials for acne vulgaris. IGA is subjective and defined by a five-grade scale of visual severity. Each grade should be “sufficiently defined to appropriately and unambiguously represent each severity grade on the scale” and success is defined by a “two grade improvement” to clear or almost clear. The OPAL study measured IGA as a secondary endpoint to help inform future trials, but the trial was not powered for this endpoint. Topline results revealed that for the 2% dose, BPX-01 demonstrated a clear numerical trend with 22.7% of subjects achieving a two-grade reduction compared to the 1% dose (16.0%) and vehicle (17.1%). These results along with an analysis of the full data will help inform the design of the upcoming Phase 3 trial this fall.

So what do the results from the OPAL trial mean for the millions of people that suffer from acne? Currently, there is a wide range of over-the-counter and prescription options for moderate-to-severe acne. The existing standard of care is to treat with oral antibiotics like tetracycline, doxycycline and minocycline that target P. acnes, the bacteria that cause acne. Topical treatments, such as benzoyl peroxide and retinoids are also commonly used in combination with oral antibiotics.

Although oral antibiotics and combination treatments can provide results for some people, there is a growing need for more safe and effective strategies. Side effects related to current treatments are a major burden for acne patients. Oral antibiotics can cause systemic side effects, including dizziness, nausea and diarrhea. Oral therapy can also continue for years and, over time, may potentially lead to antibiotic resistance. Current topical treatments are typically less effective and come with side effects, such as redness, skin irritation and flaking.

Clearly, the delivery technology and formulation of BPX-01 is intriguing and avoids many of the pitfalls of current treatments. BPX-01 fully solubilizes minocycline, increasing the efficiency of antibiotic delivery and allowing for effective topical delivery at doses much lower than oral antibiotics.

The gel is non-oily, non-staining and leaves no residue. It has demonstrated high penetration and targeted delivery of minocycline directly through the skin at the site where acne develops. It has a dual benefit of anti-bacterial and anti-inflammatory properties and a lower resistance rate than other antibiotics. By combining the efficacy of an antibiotic, the benefits of targeted application through topical delivery, and by minimizing the side effects associated with both, BPX-01 promises to be a new safe and effective option for the millions of people with moderate-to-severe acne.

Conflict of interest statement

I receive compensation from BioPharmX for my participation as a clinical trial investigator and as a consultant to the company.

CITE THIS ARTICLE:
Ted Lain, MD. Investigational Topical Minocycline Gel for Acne Advances to Phase III Development. Doctors Lounge. Available at: https://www.doctorslounge.com/index.php/articles/page/72429. Accessed August 19 2017.

References

  1. Cordain, L. et al. Acne Vulgaris: A Disease of Western Civilization. Arch Dermatol. 2002; 138:1584-1590.
  2. American Academy of Dermatology. Acne. https://www.aad.org/media/stats/conditions. Accessed May 10, 2017.
  3. Knaggs, H.E., Wood, E.J., Rizer, R.L., Mills, O.H. Post-adolescent acne. International Journal of Cosmetic Science. 2004;26(3):129-38.
  4. Mayo Clinic. Disease and conditions. Acne. 2015. http://www.mayoclinic.org/diseases-conditions/acne/basics/definition/con-20020580. Accessed May 10, 2017.
  5. Medscape. Acne vulgaris. 2016. http://emedicine.medscape.com/article/1069804-overview. Accessed May 10, 2017.

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