Narsoplimab Trial Results

EP: 1.Overview of Transplant-Associated Thrombotic Microangiopathy (TA-TMA)

EP: 2.Incidence of TA-TMA

EP: 3.Criteria for Diagnosing TA-TMA

EP: 4.Time Frame for Development of TA-TMA

EP: 5.Uncontrolled Versus Self-Limited TA-TMA

EP: 6.Risk Factors Associated With TA-TMA

EP: 7.Relationship Between TA-TMA Development and GVHD

EP: 8.Challenges of Accurate Diagnosis of TA-TMA After Hematopoietic Stem Cell Transplant

EP: 9.Interventions Used for TA-TMA

EP: 10.Practical Experience in TA-TMA Interventions

EP: 11.TA-TMA Treatment: Alternative Medications

EP: 12.Role of Leptin in the MASP-2 Pathway

EP: 13.Narsoplimab: The Phase 2 Trial

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EP: 14.Narsoplimab Trial Results

Samer Khaled, MD: Talking about the results as Christine mentioned, the response base was actually very appealing; it was 61% of all treated patients and 74% were for [per protocol set]….. Those are the patients who received 4 weeks or more on protocols; 74% had a response. We did see improvement in hemoglobin, a decrease in LDH [lactate dehydrogenase], and an increase in platelets as well. All the laboratory criteria showed improvement on those populations.

In terms of survival, for all patients at the 100% or 60% survival rate and for patients who received 4 weeks or more of treatment on the trial, there was an 83% survival grade. Patients who had response among those patients exhibit a 94% survival rate.

The overall survival for patients who had for the full-set analysis was 274 days, and…set population was 361, and responders was not reached at the time of analysis. This is really compelling data for this molecule; I don't know whether Jeff or Hari have any comments on the results.

Jeffrey Laurence, MD: I agree, they're very encouraging. We have very little to treat these patients with, and as Christine said, the more of the better. It's great to see that this study was run.

Parameswaran Hari, MD: Same thing. I think the availability of pathophysiologically targeted agent addresses what really is at the bottom of the problem, and it is a much better safety profile than some of the other agents that we have; that's the attraction. Plus we are talking about a situation very similar to second or third line treatment of GVHD [graft versus host disease] where everything is a 20% to 30% drug and suddenly we have a high response rate in the 60% to 90% range, depending on how it was used. That's actually a really good move. How often is it administered?

Samer Khaled, MD: It is being administered on a weekly basis; these patients usually are very sick and are in the hospital. The first dose or couple of doses are administered in hospital, however I have patients who were discharged and started receiving the treatment as outpatient without any problem.

Jeff, do any other comments on the treatment?

Jeffrey Laurence, MD: No; just in general we need more information on defibrotide that was mentioned. In terms of other therapies, there are several other experimental anticomplement therapies that are out there being tested on other complement mediated disorders. As far as I know, there is nothing else that is being specifically looked at in the TA-TMA [transplant-associated thrombotic microangiopathy] setting, and it looks really good for narsoplimab.

Samer Khaled, MD: The defibrotide trial was, as Hari alluded to, a very small patient population. I discussed with the company about this trial and there was about a 50% response rate, but it's a small number of patients. In some of the patients they had a combination of defibrotide with other agents; that makes it very hard to have a solid conclusion on defibrotide use. I think that that would be a good agent to test in the future prospective study.

I would like to thank all of you for this really nice and rich informative discussion. Before we conclude I would like to get some final thoughts from each of you on the exciting new development and emerging agents. We'll start with Dr Duncan.

Christine Duncan, MD: I think I get the easy choice; I get to go first. The emerging agents’ discussions have been really rich, but I were to ask or hope that people take away one thing from this discussion is to think about TA-TMA; think about your labs, look at your LDH…. If we're not thinking about it, as Dr Hari said, we can't treat it. The most important thing is to really have awareness and think about this as a significant complication of transplant.

Samer Khaled, MD: Dr. Hari?

Parameswaran Hari, MD: Yes; I agree with what Dr Duncan just said, but I'm excited that now we have agents that are targeted at the pathophysiological mechanism of the disease. We also have other complement (inaudible) antibodies (inaudible), all of which bode well for this complication.

Samer Khaled, MD: Dr. Laurence?

Jeffrey Laurence, MD: I agree; think about this disorder more and you're going to save people that way. Think about the pathophysiology; don't just tread water doing things like plasma exchange or Rituxan [rituximab] unless there's a specific indication for an auto-antibody present. Think about trials of these newer experimental agents which look very promising.

Samer Khaled, MD: Once again, thank you very much for participating in this rich discussion. To our viewing audience, we hope you found this OncLive® Peer Exchange discussion to be useful and informative. Thank you.

Transcript edited for clarity.