Thrombocytopenia was the most common adverse effect, which was managed through dose reduction.
In an interview with Pharmacy Times, Ahmed Kotb, MD, discussed findings from a trial investigating navitoclax for the treatment of myelofibrosis. In safety findings from the trial, thrombocytopenia was the most common adverse effect, which was managed through dose reduction.
Q: What were the most common adverse effects and how severe were these?
Ahmed Kotb, MD: I think it's important to look at the holistic data set. I think it's important to see the efficacy as well as the safety together. And let's look at the cohort 3. This is the cohort where navitoclax was added to ruxolitinib in the JAK-naive patient population. The primary endpoint, as I mentioned, was SVR35. And here, what we saw was about 63% of the patients achieved this endpoint at the 6-month landmark, as I mentioned, 24 weeks. This is quite unprecedented in this disease area.
What we also saw was that the longer you treated patients, more patients responded. So, we saw best overall response in about 78%. Again, this is very encouraging for us. We have a phase 3 trial that's ongoing, that is looking exactly at that, adding navitoclax-ruxolitinib versus ruxolitinib alone, so we're quite excited to see the outcomes of that study, because we believe this may be practice changing. At the same time, the other endpoints, like total symptom score reduction was about 40%. Again, very encouraging. We also saw that about a third of the patients showed a reduction in the bone marrow fibrosis. And what was very interesting was that irrespective of the amount of fibrosis the patient had at baseline, whether it was a lot of fibrosis or intermediate or a little amount of fibrosis, they had the chance to decrease this bone marrow fibrosis. So that was about 35%. So, that was also quite interesting and gives us the confidence that this agent may be having a disease modification potential.
From a side effect perspective, from an adverse event perspective, the most common adverse event was thrombocytopenia, it occurred in about 80% of the patients. It's an on-target side effect because BCL-XL, which is the target of navitoclax, is highly expressed on thrombocytopenia, thrombocytes, or platelets. So, we expected that it's a predictable and manageable adverse event. We didn't see any clinically meaningful bleeds happen in the study.
Q: How can these adverse effects be managed?
Ahmed Kotb, MD: So, so far, we have not really seen that this adverse event has impacted the outcomes of therapy. It's kind of included within the outcomes that I've just mentioned. The way we manage it within the protocol is we do reduce the dose and when it gets to a certain level, we sometimes dose interrupt. We still keep baseline therapy, which is ruxolitinib. It's also important to know that thrombocytopenia is a side effect of both the agents, navitoclax and ruxolitinib, so there is an algorithm of how this is being managed.
Q: Is there anything you would like to add?
Ahmed Kotb, MD: No, I think this is very exciting. I think that this is a new mechanism of action in a disease area that has not seen much advances over the last decades. I think we're quite hopeful that this molecule will add options to patients and to physicians. As I mentioned, we have a phase 3 trial, the TRANSFORM-1, which is running in the frontline setting. We also have a phase 3 trial that is running in the relapsed/refractory setting. We're hoping to see data from these studies by end of this year, early next year, and we will use this data to register navitoclax and hopefully bring it to patients in need. This also shows the investment that AbbVie is doing in oncology and the way we're trying to drive innovations across multiple blood cancers. We've obviously done a lot in CLL with venetoclax and IMBRUVICA. We're doing a lot also in AML with venetoclax, and we're expanding our portfolio to touch other blood cancers like lymphomas with epcoritamab, we have exciting data coming at EHA, and also you're going to see data here at ASCO from our solid tumor program. So, it really speaks to the breadth of our oncology portfolio and how we're evolving that.