Phase 2b Trial Reinforces Zasocitinib’s Safety Profile

Last month, new data on the treatment of psoriasis with zasocitinib, an oral, allosteric inhibitor of TYK2, was presented at the European Academy of Dermatology and Venereology (EADV) Congress in Amsterdam. In an interview with Dermatology Times, Melinda Gooderham, MSc, MD, FRCPC, shared pearls on this data, key takeaways from the results, and why this information is exciting for clinicians.

Transcript

Melinda Gooderham: Hi, I'm Dr. Melinda Gooderham. I'm a dermatologist and a clinical researcher from Peterborough, Ontario, Canada.

Dermatology Times: What new data on zasocitinib was presented at EADV?

Gooderham: I’m happy to share the poster that we presented at EADV looking at the changes in laboratory parameters from the phase 2b trial of zasocitinib, which was previously known as TAK-279, in this phase 2b trial, where I was an investigator. Zasocitinib was compared with placebo at a number of doses (2 milligrams, 5 milligrams, 15 milligrams, or 30 milligrams) versus placebo for 12 weeks in patients with moderate to severe psoriasis. What the poster reviewed was the laboratory parameters that were monitored throughout the 12-week study, showing that there were no changes in laboratory parameters over time, things like creatine kinase, ALT, AST, lipid values, liver parameters, were all quite stable throughout the 12-week period.

DT: From a clinician's point of view, what is most exciting about this drug?

Gooderham: From a clinician's point of view, having a drug that blocks TYK2 allosterically. There have been other TYK2 inhibitors that are competitive inhibitors that do show changes in laboratory parameters over time. But when you have allosteric inhibition, you are not at risk of binding to the competitive sites the active sites of the other JAK family molecules - JAK1, JAK2, JAK3 are not inhibited when you have allosteric inhibition of TYK2. We have 1 other allosteric TYK2 inhibitor on the market that's currently approved that we also see similar safety from a laboratory parameter perspective, where these things are not impacted. Whereas if you have a JAK inhibitor that's competitive, even though you may be selective for 1 of the family, there is some similarity between the JAK so at specific doses, you will start to block some of the other JAKs. For example, JAK2 is important for hematopoiesis. If you have any JAK to inhibition, you start to see changes in complete blood cell counts. With allosteric inhibition of TYK2 we, we do not see that. With competitive inhibition of TYK2, you may see that, but zasocitinib is an allosteric inhibitor, and so this is really reassuring to have a poster that confirms what we would expect with allosteric inhibition, and to see it so consistent across all laboratory parameters.

DT: Did the data from your research align with your expectations going in?

Gooderham: With research, there can always be a little bit of wiggle room here and there, and some things might not be as crisp and clean as what you might think they’ll come out as, but those were pretty flat lines across all of the labs.Just to pair that with the efficacy results that we see with the drug, it puts a smile on your face that we're not blocking anything else. We're blocking TYK2, the patients are getting better. We're not changing their labs. You just feel that comfort, that this is doing what we think it's doing, and to have that comfort and confidence moving forward. It does translate to the patient in that they don't have to keep going for their lab tests like with the other JAK inhibitors, because we know their labs don't change. I tell my patients that this is what the patients in the study did. All had their blood drawn all the time through the study, and we know nothing changes, so now you don't have to do it.

DT: How do you feel the AI innovations behind zasocitinib translate into these results?

Gooderham: We always say the proof is in the pudding. The medications working better, higher PASI 100 rates. We're not seeing any any changes in laboratory parameters. The safety profile is very clean, what we would expect with TYK2 inhibition. I trust the scientists to do their job, and I have the confidence to prescribe it to my patients.

DT: What are your biggest takeaways from this data?

Gooderham: Because of this data, we're into phase 3. I'm an investigator in the phase3 program, so I already have the next wave of patients who are benefiting from zasocitinib. Again, with this data, I can feel confidentwhen I'm explaining this study to the patient to see if they want to participate. I can share this type of data from this poster with them and saywe know that this doesn't affect any of your other lab tests. We'll still do the labs in a phase 3 manner, butit gives the patient the comfort and gives me the confidence to recommend the study and the medication. It could absolutely be 1 pill once a day, no laboratory monitoring for patients with psoriasis. I think that's what a lot of patients are looking for. Some patients may prefer biologics, some patients prefer an oral therapy, and with the levels of efficacy and the safety that we're seeing, I think definitely could be first line therapy. It'd be nice if we could get it approved in a younger population eventually, too, because I think they would appreciate that.

[This transcript has been edited for clarity.]