Written by Peter G. Traber, M.D. on September 24, 2015
Serendipity, or fortunate happenstance, has always been an important part of the search for medicines. As pointed out by Thomas A. Ban (1), serendipity in drug discovery is more than just luck, but rather is best described by Pasteur’s famous quote that “Chance favors the prepared mind”. Serendipity may have entered our development program with our anti-galectin drug, GR-MD-02, and today we kick off another Phase 2 clinical trial to test whether an unexpected effect observed in our Phase 1 trial is truly something of significance.
Our surprising clinical trial observation
In the course of our Phase 1 clinical trial of GR-MD-02 in patients with fatty liver disease (NASH) and advanced fibrosis, we encountered a patient with plaque psoriasis, who happened to be one of the patients treated with four infusions of 4 mg/kg of GR-MD-02. Psoriasis is a relatively common, chronic skin disorder that causes a red, thickened and scaling rash that can cover many parts of the body.
Upon the patient’s follow-up visit to her physician, she reported resolution of her long-standing psoriasis. In an interview with a dermatologist and myself, the patient confirmed that she had severe psoriasis involving much of both arms continuously for six years. Following treatment with GR-MD-02, the psoriasis resolved and has not recurred for over a year! There was another patient in the study with mild psoriasis who was able to reduce use of topical steroids and another with severe psoriasis who had just been withdrawn from therapy with Stelara (ustekinumab), a powerful injection therapy for psoriasis, who did not improve.
Observation prompts exploratory clinical trial
On the strength of the marked effect in the one patient, both a dermatologist investigator and we felt it was worth investigating whether this was a real effect of GR-MD-02. In addition to the clinical finding, research publications suggest the potential importance of galectin-3 in psoriasis (2, 3). Therefore, we initiated a phase 2a, open label clinical trial in patients with moderate to severe plaque psoriasis (press release September 22, 2015). In this trial, 10 psoriasis patients with ≥ 10% of their skin affected and a PASI (psoriasis activity and severity index) of ≥ 12 points will be treated with 7 every other week infusions of 8 mg/kg GR-MD-02. The severity of psoriasis was agreed upon with the FDA as warranting experimental therapy. More information on the trial can be found at: https://clinicaltrials.gov/ct2/show/NCT02407041?term=GR-MD-02&rank=5
The primary endpoint for evaluation of these patients will be the PASI-75, which means that they have had a 75% improvement in the severity of the disease 30 days following the final infusion. This is a standard endpoint used in studies of drugs that have been approved for marketing. The PASI system assesses each affected body area as to the extent of skin redness, thickness, and scaling. We intend on reporting data 30 days following treatment of the last patient treated. Additional results would then be reported following 6 month and 1 year follow up periods to assess for durability of response.
What is next following exploratory trial?
Our current trial is based on an observation with one patient. It is promising enough to investigate in an exploratory trial, but single-patient observations are notoriously unreliable. Therefore, while we anticipate results, we are cautious in our optimism.
We will consider this clinical trial successful if ≥ 50% of patients treated meet the primary efficacy endpoint. Positive results from this trial would be significant, since we would have demonstrated a potentially important clinical effect of our galectin-3 inhibiting drug, GR-MD-02. Moreover, it is of interest that there is a relatively high incidence of NASH in patients with psoriasis (4, 5), which is our other major indication for GR-MD-02.
With positive results, we will then consider entering into a development program aimed at marketing approval for psoriasis. There are already multiple excellent drugs on the market for this indication, some of which have been approved in the last few years. Potential areas that GR-MD-02 may be differentiated from other drugs include safety, prolonged response (if the one patient results are confirmed), and lower cost manufacture.
These “CEO Perspectives” will be a regular feature of our communication activities and may contain forward looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements relate to future events and use words such as “may,” “could,” “expect” and others. These statements include those regarding the hope that Galectin’s development program for GR-MD-02 will lead to the first therapy for the treatment of fatty liver disease with advanced fibrosis and cirrhosis. For a discussion of additional factors impacting Galectin’s business, see the Company’s Annual Report on Form 10-K for the year ended December 31, 2014, and subsequent filings with the SEC. You should not place undue reliance on forward-looking statements. Although subsequent events may cause its views to change, management disclaims any obligation to update forward-looking statements
Please look for future editions in which multiple aspects of our development programs for unmet medical needs will be addressed.
1. Ban TA. The role of serendipity in drug discovery. Dialogues Clin Neurosci 2006;8(3):335-344.
2. Chen HY, Lo C-H, Li C-S, Hsu DK, Liu FT. Galectins and cutaneous immunity. Dermatologica Sinica 2012;30:121-127.
3. Lacina L, Plzakova Z, Smetana K, Jr., Stork J, Kaltner H, Andre S. Glycophenotype of psoriatic skin. Folia Biol (Praha) 2006;52(1-2):10-15.
4. Roberts KK, Cochet AE, Lamb PB, Brown PJ, Battafarano DF, Brunt EM, et al. The prevalence of NAFLD and NASH among patients with psoriasis in a tertiary care dermatology and rheumatology clinic. Aliment Pharmacol Ther 2015 Feb;41(3):293-300.
5. Wenk KS, Arrington KC, Ehrlich A. Psoriasis and non-alcoholic fatty liver disease. J Eur Acad Dermatol Venereol 2011 Apr;25(4):383-391.