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SynAct Pharma announces outcomes of the independent audit of the 4-week RESOLVE P2a clinical trial in Rheumatoid Arthritis
Prenumeration
Beskrivning
| Land | Sverige |
|---|---|
| Lista | Small Cap Stockholm |
| Sektor | Hälsovård |
| Industri | Bioteknik |
In November 2023 SynAct Pharma reported that during the evaluation of the data from part A of the RESOLVE study, a four-week dose range study of resomelagon (AP1189) in rheumatoid arthritis patients with an inadequate response to methotrexate treatment, issues were identified that needed further evaluation and initiated an audit of the study by an independent third-party auditor.
The independent audit has identified that safety data from all sites should be included in the product safety base and that drug exposure and efficacy data could be utilized for further assessment except for the data from one site where drug exposure and efficacy data should be excluded.
The analyses of the study identified a large degree of heterogeneity in the recruited patient population. Two-thirds of the patients had been on methotrexate (MTX) treatment for more than one year at the time of recruitment, with most patients being treated for over 2 years with only 5 completed patients having a medical history of initiation of MTX treatment within 6 months of RA diagnosis. In addition, medical history, as reported, did not support treatment with maximal tolerable dose of methotrexate in a fraction of the recruited patients. In total 125 patients were included of which 107 completed Resolve Part A per protocol with daily doses of placebo, 60mg, 80mg or 100 mg resomelagon for 4 weeks in addition to a stable dose of MTX.
As efficacy data from one site has to be excluded from the efficacy analyses, SynAct is awaiting final efficacy assessments from the contract research organization (CRO) with the site removed from the calculations. However, the study showed a very high placebo effect with ACR20, the primary efficacy readout, around 50% at 1-month and with lower numbers reached in the three active groups.
Resomelagon continued to be generally safe and well tolerated relative to placebo. One serious adverse event (SAE) was reported in the study in a placebo treated patient that was hospitalized due to severe exacerbation in joint pain. The total number of treatment emergent adverse events (TEAEs) reported was 56 in the 125 recruited patients with 16 in the placebo group and 10, 12 and 18 in the 60mg, 80mg and 100mg resomelagon groups, respectively.
“Current international treatment guidelines (ACR 2021; EULAR 2022) recommend implementing second line treatment in patients having an inadequate response to MTX after 3 to 6 months of treatment. The majority of the patients in the Resolve Part A did not fit into this treatment approach, but were more chronic patients, many treated for years in non-optimal ways, which most likely explain the high placebo effect reported” says Thomas Jonassen CSO, SynAct Pharma. “We know from the EXPAND study that treatment with resomelagon should be implemented in patients with signs of systemic inflammation who are preferably early in their disease development. The EXPAND study also clearly showed that the treatment effect in the relevant patient population developed during the full 12 weeks treatment period. The lack of treatment effect of the compound in the current study is therefore likely impacted by the heterogeneity of the population recruited and the short treatment period.”
As Resolve Part A was not able to identify doses of resomelagon to be applied in part B of the RESOLVE study, a 12-week Phase 2b study in DMARD-IR patients. Phase 2b development of resomelagon in DMARD-IR patients will be postponed until the compound has been tested in the relevant patients, ie tested as a 12-week second line treatment option in RA patients showing an incomplete response to their initial course of MTX treatment, primary DMARD-IR.
The company is in discussion with the CRO who ran the Resolve Part A study as a full service CRO with the aim to get the study duly reported and the project back on track in the most effective way.
For further information, please contact:
Torbjörn Bjerke, CEO
Phone: +46 70 205 58 40
Mail: tbje@synactpharma.com
Thomas Jonassen, CSO
Phone: +45 40 15 66 69
Mail: tj@synactpharma.com
About SynAct Pharma AB
SynAct Pharma AB (Nasdaq Stockholm: SYNACT) is a clinical stage biotechnology company focused on the resolution of inflammation through the selective activation of the melanocortin system. The company has a broad portfolio of oral and injectable selective melanocortin agonists aimed at inducing anti-inflammatory and inflammation resolution activity to help patients achieve immune balance and overcome their inflammation. For more information: www.synactpharma.com.