Nyligen meddelade SynAct Pharma att de har lämnat in en ansökan om start av klinisk prövning för den kliniska fas IIb-studien EXPAND på patienter som nyligen diagnosticerats med reumatoid artrit. Syftet är att bekräfta positiva fas IIa-resultat för AP1189 och substansens fulla effektpotential. Bolaget godkändes nyligen även för notering på Nasdaq Stockholms huvudlista med förväntad första handelsdag den 12 juli. BioStock fick en pratstund med SynAct Pharmas vd Jeppe Øvlesen och CSO Thomas Jonassen.
SynAct Pharmas läkemedelskandidat AP1189 riktar selektivt in sig på melanokortinsystemet för behandling av inflammatoriska sjukdomar. Syftet är att inducera upplösning av inflammationen genom att balansera det inflammatoriska svaret, utan att hämma immunsystemet. Stärkta av lovande fas IIa-resultat från BEGIN-studien har bolaget beslutat att fortsätta den kliniska utvecklingen inom reumatoid artrit (RA) i två kliniska fas II-studier – EXPAND i nydiagnostiserade RA-patienter och RESOLVE på DMARD-IR-patienter.
Inskickad CTA för EXPAND
SynAct Pharma har lämnat in en klinisk prövningsansökan (CTA) för EXPAND och inväntar nu godkännande att få starta studien. EXPAND kommer att omfatta 120 behandlingsnaiva RA-patienter, det vill säga patienter som ännu intehar behandlats för sin sjukdom. I studien kommer 100 mg AP1189 att ges i kombination med metotrexat (MTX),vilket är en vanlig första linjen-behandling för RA.
Syftet med EXPAND-studien är att bekräfta säkerhets- och effektresultaten från BEGIN och identifiera den fulla behandlingspotentialen, samt möjliggöra utveckling i sen klinisk fas. Målet är att rekrytera den första patienten under Q3 2022 och rapportera studiedata före utgången av 2023.
Bekräfta tidigare resultat och utforska full potential
I BEGIN visade AP1189 god säkerhet och tolerabilitet och, inte minst, kliniskt meningsfull effekt hos RA-patienter redan efter 4 veckors behandling. 100 mg AP1189 dagligen i kombination med MTX gav en signifikant minskning i sjukdomsaktivitet (Clinical Disease Activity Index). I EXPAND kommer doseringsperioden att förlängas från 4 till 12 veckor och de nya AP1189-tabletterna kommer att användas, vilket förväntas kunna ge ännu bättre behandlingsresultat enligt bolaget.
SynAct Pharmas vd ser fram emot att starta EXPAND
BioStock kontaktade SynAct Pharmas vd Jeppe Øvlesen för att ta del av hans förväntningar inför EXPAND-studien.
First of all, how does it feel to soon be able to initiate SynAct Pharma’s first phase IIb study?
– It is a major step for us to be able to initiate a phase IIb study. We are in a very exciting position where we have successfully completed a phase IIa study in newly diagnosed RA patients and are now taking a step up to a larger study with longer treatment period. A CTA has been submitted for the EXPAND study and our RA development activities are conducted according to plan.
– I would also like to mention that we have now been approved for listing on Nasdaq Stockholm, which is another milestone for us and our shareholders.
Where will the patients be recruited and how long time do you expect it to take?
– The study will be conducted in Moldova and Bulgaria, as the BEGIN study, and potentially in other European countries as well. We expect to get the CTA approval during the summer and then initiate patient recruitment after the summer break.
– In the BEGIN study, we were able to recruit almost half the patients at 6 sites in the selected countries within 6 months. Now we have doubled the number of sites, so we believe that it is absolutely possible to recruit the 120 patients for the EXPAND study during the planned recruitment phase.
»Now we have doubled the number of sites, so we believe that it is absolutely possible to recruit the 120 patients for the EXPAND study during the planned recruitment phase.«
– We will dose AP1189 on top of the MTX treatment for 12 weeks, in line with recommendation from the current guidelines for development of new compounds in RA. The ambition is to present data during the second half of 2023.
Is there a risk that the EXPAND study could be affected by the situation in Ukraine?
– We have a plan and additional sites ready if our study in any way would be affected by Russia’s invasion of Ukraine. But so far, the activities at the hospitals are completely normal and we have seen a lot of interest from investigators who would like to participate in the EXPAND study.
You and CBO James Knight recently participated in BIO International Convention 2022 in San Diego – how was the event?
– We were very busy and had more than 35 interesting meetings with potential partners. As I mentioned earlier, it is clear that we are now in a very exciting position. If we can present a positive outcome from the EXPAND study, we would have a very attractive asset and additional phase II results strengthening our case in RA.
»We had more than 35 interesting meetings with potential partners. As I mentioned earlier, it is clear that we are now in a very exciting position.«
CSO ger mer information
BioStock kontaktade även SynAct Pharmas CSO Thomas Jonassen för mer djupgående information om utvecklingsaktiviteterna inom RA.
Could you tell us a bit more about the patient group in the EXPAND study?
– The patient group in the EXPAND study will be very similar to the one in the BEGIN study. The patients are recently diagnosed with RA and have a score over 22 on Clinical Disease Activity Index (CDAI), a scoring system that is easy to handle in the daily clinic and used more and more in the clinic to evaluate progress in treatment effects. If you have a CDAI higher than 22, then you are considered to have high disease activity.
– These patients, and even those with moderate disease activity, will typically be allocated to treatment with disease modulating anti-inflammatory agents, so-called DMARDs. The first-line treatment is Methotrexate (MTX), which originally was developed as a cancer therapy, but in lower doses is used widely in RA.
– In the Nordics, we have relatively new guidelines with quite an aggressive dose regimen, where you start on 10-15 mg MTX and then as fast as possible increase to 25 mg. Glucocorticoid (GCs) treatment is usually also added, not at least given as injection into the joints. In the EXPAND study, we will mimic the treatment approach in the US, which is more conservative with regard to increasing the dose of MTX and the use of GCs. The more conservative approach is explained with the unwanted side effects profiles of MTX and GCs.
What results do you want to obtain in the EXPAND study?
– The ultimate ambition of a treatment regiment is to induce remission, i.e. bring the disease activity down to low disease activity, as well as reduce fatigue, disability etc. However, the primary goal in EXPAND is not to reach disease remission within 12 weeks. Actually, in many patients this can only be achieved by use of GC treatment associated with often quite severe side effects.
– Consequently, the primary efficacy read-out is the proportion of patients achieving a 20 per cent improvement on the American College of Rheumatology scoring system, ACR, at 12 weeks relative to placebo. What we saw in the BEGIN study was that 60 per cent qualified for the ACR20 after four weeks of treatment, which is comparable to what is seen following treatment with JAK inhibitor, a class of drugs that are very effective. However, they are labelled with black box warnings due to severe side effects, and recently FDA changed the label for some of them so the use should be restricted to patients who do not respond to second-line treatment.
Do you believe that the prolonged dosing in EXPAND can provide even better efficacy results than shown in BEGIN?
We believe that the response rates will increase with the prolonged dosing. The ambition is to show treatment effect (ACR20) in 75-80 per cent of the patients after three months of dosing with AP1189, which is in the range of three months data for JAK inhibitors.
»We believe that the response rates will increase with the prolonged dosing. The ambition is to show treatment effect (ACR20) in 75-80 per cent of the patients «
– The results from the BEGIN study looked very good and we are also very optimistic about the EXPAND study. We hope that we can continue to show a good safety profile.
– Since AP1189 is a resolution therapy, and not an immunosuppressive treatment, the risk of suppression of the immune system and thereby the risk to get infections is reduced. Infections are otherwise a side effect that is typically associated with RA drugs and other inflammatory diseases. Our approach, which we can confirm in the EXPAND study, could be a game-changer as we modulate the immune system, rather than blocking it. Actually, that is probably what makes us stand out.
Could you tell us a bit more about the potential clinical benefits of first-line treatment with AP1189 in combination with MTX?
– If we will be able to show that the combination is well tolerated and has an additive effect, it could potentially reduce the need for increased doses of MTX and the need to treat with glucocorticoids.
Why have you decided to focus the clinical development on both DMARD-IR patients with insufficient response to MTX and newly diagnosed, previously untreated RA patients?
– I think the reason is quite clear – there is a huge market and request for new treatments from DMARD-IR patients. These patients have been treated with first-line treatment for at least three months and still have significant symptoms. New treatment alternatives for these patients are what patients, rheumatologists and pharma companies, i.e. potential partners, are looking for.
– However, we also want to take advantage of the opportunities in treatment-naïve patients, especially since we already have seen great results with AP1189 in these patients. But from a commercial perspective the biggest market is in DMARD-IR.
Could you also give us an update on the interactions with FDA regarding the RESOLVE study in DMARD-IR patients?
– We have presented the intended setup of the RESOLVE study to the FDA and got the written response from them earlier this week. The next step is therefore to continue the Investigation new drug (IND) application and start part A of RESOLVE, which is a dose range study for four weeks to identify relevant doses to part B – a phase IIb study with a larger patient population and 12 weeks of dosing. We intend to file the IND following by initiation of the study during the autumn.
»We are working on new compounds and hope to be able to communicate more on this during the second half of the year.«
What other development activities are you focusing on right now?
– We also see a large potential of the compound in the nephrology space and look very much forward to get the amended study in nephrotic syndrome (NS) up and running.
– Beside the clinical programmes, we are working on new compounds and hope to be able to communicate more on this during the second half of the year.Innehållet i BioStocks nyheter och analyser är oberoende men BioStocks verksamhet är i viss mån finansierad av bolag i branschen. Detta inlägg avser ett bolag som BioStock erhållit finansiering från.