SynAct Pharma has completed the patient recruitment to the phase IIb trial EXPAND with resomelagon (AP1189) in newly diagnosed, severe rheumatoid arthritis. The last patient was enrolled well ahead of schedule, enabling reporting of top-line data in about five months. The company’s CSO Thomas Jonassen commented on the progress to BioStock.

SynAct Pharma conducts research and drug development in inflammatory diseases targeting a novel treatment approach aimed to stimulate resolution of inflammation. The company’s lead compound, resomelagon (AP1189) promotes inflammatory resolution through selective activation of melanocortin receptors 1 and 3.

SynAct Pharma currently has three ongoing clinical trials with resomelagon (AP1189), two of which are in rheumatoid arthritis (RA). The company recently announced in a press release that one of the studies, EXPAND, is fully recruited:

»It’s satisfying to announce that the last patient in the EXPAND study was enrolled well ahead of schedule. We now look forward to completing the dosing and reporting the study. « – Thomas Jonassen CSO of SynAct Pharma

Progress in EXPAND study – patient recruitment concluded

EXPAND is a 12-week phase IIb trial evaluating resomelagon (AP1189) in newly diagnosed, treatment naïve patients with severe disease activity. A total of 127 patients have been randomised to either active treatment with 100 mg tablets of resomelagon (AP1189) or placebo tablets. The dose is given once daily in combination with the prescribed dosing of the first-line treatment Methotrexate.

SynAct Pharma expects to complete the dosing of all patients in July and conduct the last patient’s follow up visit in August. After that, the key results will be presented in a press release and an investor call.

Continuation of the BEGIN study

The EXPAND study is conducted to confirm the results from the BEGIN study where resomelagon (AP1189) showed a favourable safety profile and clinically meaningful effect, with a significant reduction in Disease Activity Index already after four weeks of treatment.

BioStock contacted SynAct Pharma’s CSO Thomas Jonassen to learn more about why the EXPAND study is being conducted and how the study is progressing.

Thomas, could you elaborate on why you decided to initiate the EXPAND study following the BEGIN study?

– The results of the BEGIN study showed statistically significant and importantly clinically meaningful reduction in disease activity of resomelagon (AP1189) already after 4-weeks of dosing.

– When given in combination with first-line treatment methotrexate (MTX) we showed a 60% improvement relative to placebo when evaluated by reduction in disease activity. Evaluated through the commonly used ACR scoring system, we saw that more than 60% on resomelagon responded compared to 33% of those treated with placebo. That is a response rate comparable to the very effective JAK inhibitors which, unfortunately, have an unwanted side effect profile limiting its use as first-line treatment. Resomelagon showed an attractive side effect profile, so it was logical to continue development to show the full treatment potential of the compound together with MTX in a longer study.

»Resomelagon showed an attractive side effect profile, so it was logical to continue development to show the full treatment potential of the compound together with MTX in a longer study.«

What factors have made it possible to complete the patient recruitment earlier than expected?

– We are fortunate to work with very dedicated investigators, many of whom also participated in the BEGIN study. We, of course, had patients who for various reasons did not qualify to participate in the study, but only a few declined to participate once they had the chance to read the patient information. Offering a patient-friendly treatment with a small tablet to be taken once daily, of course, also played a role.

What study outcomes are crucial for further development of AP1189 in RA?

– Two things are of outmost importance. We need a good safety profile and, importantly, confirm that our treatment approach, aimed at stimulating inflammatory resolution, does not induce immunosuppression. Compared to most other current treatment approaches, an important factor is that we modulate and not suppress the immune system.

»Compared to most other current treatment approaches, an important factor is that we modulate and not suppress the immune system.«

– The treatment efficacy is also equally critical. Here, we don’t think that we need to show superiority to current treatment approached. If we show a good safety profile, then a smaller max response than what has been reported in the literature could be fine as long as we are better than the controls (MTX + placebo). And when we mean better, we should not only look at difference to the placebo group and the end of the treatment period, but also how fast we reach improvements.

– The use of glucocorticoids (GC) is another important factor. The current treatment guidelines recommend controlled use of GC, but preferable as local injections into the joints and if given orally, then with as low a dose as possible. GCs are associated with a long list of unwanted side effects. Nevertheless, they are widely used. In many clinical studies, even when a compound is tested as first-line therapy, up to 50% or more of the patients are treated with GC. In our study GCs are not allowed unless you get severe exacerbation in disease activity, then the investigator can use GC as rescue medicine. If we can show good treatment effects in the absence of GCs, we think that we’ll have something of great value.

»It is an exciting time for SynAct. The data we collect in the second half this year will be critical for the next phase of the company’s growth. Business development activities have been ongoing, and we are seeing good interest from big pharma and larger biotech companies«

Besides the finalisation of the EXPAND study, what else can we expect from SynAct Pharma in the short term?

– From a development perspective we also have the RESOLVE part A study where we currently are recruiting in a 4 weeks combined safety and dose range study in what is called DMARD-IR patients, those with uncontrolled RA after being treated with MTX for at least 3 months. Actually, many of the patients have as high disease activity as what we have seen in the patients recruited in the EXPAND study.

– The plan for the RESOLVE part A study, which we are running both in Europe and the US, is to report data in the second half of the year. We look very much forward to getting these data which will give the possibility to set the doses to part B of the study, a 12 weeks phase IIb study where we have approval to test up to 3 doses of resomelagon (AP1189) vs placebo.

– In addition to our RA studies we have a number of important ongoing activities. This includes our study in nephrology, planned to report key results by the end of this year. Also, the in vivo pharmacology program which will support an upcoming clinical study with the peptide TXP-11.

– It is an exciting time for SynAct. The data we collect in the second half this year will be critical for the next phase of the company’s growth. Business development activities have been ongoing, and we are seeing good interest from big pharma and larger biotech companies.

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