The first readout from Coegin Pharma’s COAK phase I/II study in actinic keratosis has produced positive results. The top-line data indicates excellent safety and tolerance of AVX001 in 60 patients evaluated with two different doses. BioStock reached out to Coegin’s CEO Tore Duvold to get his perspective on the data.

Nordic biotech Coegin Pharma is offering a novel treatment approach against cancer and inflammation with both small molecules and peptide-based drug candidates.

One of the company’s focus indications is the pre-cancerous condition actinic keratosis (AK), a common disease of the skin. AK presents itself with multiple rough or scaly spots on the upper-most layers of the skin caused by chronic inflammation after prolonged exposure to the sun.

Read more about Coegin’s therapeutic approach and AK here.

AVX001 in clinical evaluation

Thanks to years of pioneering research led by Professor Berit Johansen at the Norwegian University of Science and Technology (NTNU), Coegin has developed, and is currently evaluating, drug candidates able to target the cPLAa family of enzymes, which have been found to be involved in a wide range of inflammatory diseases, including cancer.

Lead candidate AVX001 just completed a phase I/II trial called COAKS (Copenhagen Actinic Keratosis Study), being evaluated as a potential treatment for AK. The trial was initiated during the fall of 2021, and it included 60 patients divided into three dosing groups – 1 or 3 per cent concentration of AVX001, and placebo.

Positive data readout

Last week, Coegin announced a first readout of results from the study, which gives AVX001 a positive safety and tolerance profile. Investigators looked at local skin reactions during treatment with AVX001, and none of the 60 patients included in the study experienced any adverse events, and only two patients got mild local skin reactions which disappeared at end of study.

Professor Merete Hædersdal, the Principal Investigator of the COAK study, had this to say about the results in a press release:

»In the COAK study, we saw almost no local skin reactions, indicating that AVX001 is well tolerated. This is in contrast to many other existing treatments that show skin reactions that are difficult for patients to tolerate. We hope that further studies with AVX001 can bring us closer to our goal of launching an effective product that patients can benefit from.«

While safety and tolerability were the primary objectives of the study, secondary objectives like efficacy and quality of life also looked promising. 15 per cent of patients treated with active doses achieved clearance (i.e., more than 50 per cent reduction in actinic keratosis lesions). Additionally, 74 per cent of patients treated with 3 per cent AVX001 achieved an improvement in their AK lesions. Despite not being statistically significant due to the low number of test subjects, the results point to positive efficacy as well.

Comments by the CEO

BioStock got in touch with Coegin’s CEO Tore Duvold to get his take on the importance of these results and what they mean for the company as it moves forward with the clinical evaluation of AVX001.

»The excellent safety and tolerability are clearly a unique selling point for AVX001. Although the trial was designed for safety, we also see clear trends that the product improved the condition for AK patients. It is only a four-week trial with once daily treatment, and we are therefore convinced that it is realistic to obtain good effect in an optimised study designed for efficacy.« — Tore Duvold, CEO coegin Pharma

Tore Duvold, could you expand on these top-line data from the COAK study? How important are they?

– We are obviously very pleased to see that the product is very safe and well tolerated which was also the primary objective. Remember that most of the available topical treatments for AK cause harsh local skin reactions that can last for a long period of time. Imagine going around with a large red lesion or skin erosions in your face for weeks which, by the way, can also be quite painful. The excellent safety and tolerability are clearly a unique selling point for AVX001. Although the trial was designed for safety, we also see clear trends that the product improved the condition for AK patients. It is only a four-week trial with once daily treatment, and we are therefore convinced that it is realistic to obtain good effect in an optimised study designed for efficacy.

The data suggests that the secondary objective of efficacy was also reached. However, the results were not statistically significant. How confident are you that the positive efficacy trends seen so far will persist in the next study?

– The secondary endpoint related to efficacy showed that a few patients obtained clearance above 50 per cent, which may not seem high at first sight. However, 74 per cent of the patients obtained improvement with the 3 per cent dose, and none had a worsening of their condition. We think this is positive and encouraging for such a short trial. Most topical drugs for AK need to be taken for several months and often several times per day in order to obtain efficacy. And, as I said before, most of them cause harsh local skin reactions with large red lesions which are often painful. It Is clear that the next study needs to be optimised in order to demonstrate that a large proportion of the patients can get a good effect of the treatment. We have learned a lot from this study, and we have concrete ideas how we can optimise the treatment to achieve good efficacy.

This is an initial readout. What comes next for this project?

– I think the optical coherence tomography (OCT) data can be very Interesting and provide useful information about how the AVX001 acts in the skin over time. OCT uses light waves to take cross-section pictures of the skin. OTC, which is a non-invasive imaging test that was used before, during and after treatment. These data and images can potentially tell us more about how the drug works over time and give useful guidance to the continued development for AK and basal cell carcinoma (BCC).

Finally, if the positive indications in terms of safety and efficacy would be confirmed in later studies, what implications could that have for actinic keratosis patients in need of better treatments?

– It is certainly positive, and it gives us the opportunity to continue the development of a much safer but also an effective and convenient drug for the treatment of AK and potentially also BCC. We want to complete the analyses of all the data before we can decide on the next trials. It is also very satisfying that we have been able to establish and conduct this digitally supported trial in such a short time and with very limited costs during the peak of the COVID pandemic. We have been privileged to work with so many dedicated experts in actinic keratosis, clinical trials and digital tools. I am impressed and grateful for their excellent work and I look forward to continuing the collaboration.

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