Pharma Strategy Blog

Greetings from the annual American Society of Hematology (ASH) meeting in San Diego!

The palm trees and warm sunshine here were a most pleasant welcome after the bitter chill in Texas.

Having just arrived here from the San Antonio Breast Cancer Symposium, I thought it would be a nice idea to do a quick preview of some of the new and interesting data that I’m interested in at this conference and share some of the hot topics that I’ll will be following over the weekend:

• Ponatinib in refractory CML
• In myelofibrosis, rixuluximib and CYT-387
• Velcade and pomalidomide in multiple myeloma
• Obinutuzumab, PCI-32765 and alisertib in lymphomas

Let’s take a quick look at these topics in turn.

CML

The updated phase II PACE trial is expected to be presented at this meeting. Ponatinib is a potent second generation BCR-ABL inhibitor that also targets FLT3 and FGFR. The initial indication is expected to be in relapsed, refractory CML after prior treatment with a minimum of two TKIs, although many are likely to have received imatinib, dasatinib and nilotinib, so a heavily pre-treated population. Patients with advanced CML or Ph+ ALL received ponatinib in a single arm open-label trial. The other thing to note is that this agent is the only TKI so far shown to target the rare T315I mutation and these patients were included in the study.

If the results continue to hold up for durability with no additional safety signals since FLT3 and FGFR may induce off-target side effects, then I’m expecting Ariad to file ponatinib for accelerated review with the FDA, based on phase II data in relapsed and refractory CML, sometime in 2012. This is an exciting new agent and it will good for patients with CML to have an additional option in this setting.

MYELOFIBROSIS

This year has seen a lot of interest in myelofibrosis with Incyte’s ruxolitinib (Jakafi) receiving FDA approval recently. The drug was approved largely on the basis of its ability to reduce spleen size, which is one of the complications of the disease. The updated phase III COMFORT-1 data is being presented on Monday and my assumption is that we will see an improvement in overall survival with ruxolitinib.

There has been a lot of interest in YM Bioscience’s agent, CYT-387, which caused a stir at ASCO after initial data suggested that it may be able to reverse anemia associated with the condition.

Now, I’m not sure of the exact mechanism behind this phenomenon, since both compounds target JAK1 and JAK2, so the anemia response may be an artifact or a real effect. If the anemia effect is real, then I’m expecting to see the hemoglobin levels to go up rather than down, as we saw with Jakafi. The poster on Monday may well tell us more about what’s happening here and also I’m hoping to speak to some myelofibrosis thought leaders to see what their perspective is.

MYELOMA

Multiple myeloma has seen real improvements in overall survival over the last 10 years with the introduction of bortezomib (Velcade) in the upfront setting and lenalidomide (Revlimid) in the refractory and maintenance settings. Currently, a new kid on the block, Onyx’s carfilzomib, is currently being reviewed by the FDA in the refractory population, although we likely won’t know the decision until 1Q next year. If approved, it may offer physicians a new option to extend outcomes even further in advanced myeloma.

There is another agent not far behind, pomalidomide, which is a third generation immunomodulatory agent similar to lenalidomide. Celgene are presenting key data at this meeting and I’m looking forward to seeing how the data is progressing. I’m expecting this compound to show good efficacy in advanced myeloma, as it is thought to be more potent than Revlimid.

The phase III multiple myeloma study that is of great interest is the VISTA trial, which will be presented on Monday and compares the combination of Velcade, melphalan and prednisone (VMP) with melphalan and prednisone alone (MP). The five year data in treatment naive multiple myeloma will inform us which combination has superior overall survival and side effect profile and what can be expected in terms of secondary primary malignancies (SPM) with the triple versus double combination over longer term follow-up.

LYMPHOMAS AND CLL

For me, the big lymphoma story at this ASH is probably going to be GA101, now named obinutuzumab. It’s a CD20 antibody similar to, but also different from, rituximab, making it ideal for testing in NHL since the proof of concept is already established for the CD20 target.

My critical questions related to this agent’s development are:

1. Will it overcome rituximab resistance and work in refractory patients?
2. Will it work more effectively than rituximab earlier and prolong outcomes further?
3. Will it have fewer side effects than rituximab?

If any of the above are true, how does obinutuzumab work differently than rituximab and does that explain any of the differences?

Not all of these questions will be answered here at this ASH meeting, but I’ll discuss these issues in more detail once the data is available.

Finally, there are a couple of other compounds in early development for lymphomas that I’m really interested in.

The first is PCI-32765 (Pharmacyclics), a bruton kinase inhibitor (BTK), while the second is Millennium and Seattle Genetics’s aurora kinase A inhibitor, alisertib. These are relatively new mechanisms of action in lymphomas and intriguing scientifically.

I’ll write more about these particular agents in depth as the data becomes available, but they’re worth watching out for over the weekend as the wires hit the news sites.

Meanwhile, you can follow the conversations at the American Society of Hematology meeting on Twitter using the official hashtag of #ASH11.

Do check back for daily updates here in the blog for the hot (and sometimes not so hot) data. I’ll also be posting a video review of the important news next week.