Saturday, May 18, 2013

GA-101 aka. obinutuzumab in CLL

I love it when a drug comes out of nowhere to suddenly become the hottest thing around...  The latest recipient of that distinction is obinutuzumab.

The annual mega-conference ASCO (american society of clinical oncology) starts up in the last few days of this month.  There are a few big papers for CLL/NHL patients.  I hope to capture the highlights over the next few weeks as I put out updates.

One thing to be VERY careful about is the misuse of the term, "significant."  There is a huge difference between something that is "statistically significant" (ie. a comparison in which the results are unlikely to have occurred by chance) and "clinically significant" (ie. this makes a genuine difference for patients with the disease).  Read my prior post about how things get mischaracterized as "significant."

So what are the big updates this year?

Ibrutinib is in a data lull between the mature reports of the early studies and the ongoing registration studies that have not yet reported.  There is a fantastic piece about ibrutinib resistance that I put up a few days ago.  Idelalisib is still reporting out the mature results of early studies.  Phase III trials are ongoing.  I've been after them to get their phase I studies published but they have been quite slow getting those out the door.

GA-101 (also named obinutuzumab) has a very important presentation.  Rituxan comes off patent pretty soon - hopefully that would lower drug costs (although in this case - maybe not so much).  While the regulators and industry are all tied up in knots over how to make a generic antibody - Roche has set out to make a better version of the drug - see my post on building a better CD20 antibody.

Our first peak into the "efficacy" of GA-101 came last year at ASH where it was compared straight up head to head with rituxan in relapsed indolent non-hodgkin's lymphoma.  Patients got a dose of either drug once per week then once every two months for two years.

There was a suggestion that patients in the GA-101 arm had a higher response rate compared to rituxan.  Unfortunately when you figured out how long the responses lasted it was pretty equal for both groups.  It was interesting to watch the response.  I think the sponsors were excited to see the increased response rate but a lot of investigators sort of yawned.... yup, just another CD20 antibody - not much to see here.

That is why this ASCO presentation of GA-101 in patients with CLL is so exciting - there is something really different here!

GA-101 was studied in the German CLL 11 study.  This was a three arm study in which chlorambucil was compared to chlorambucil in combination with either rituximab or GA-101.  The study included elderly (average age 73) individuals with decreased kidney function (necessary for fludarabine elimination from the body), or a bunch of other medical problems as defined by the Cumulative Illness Rating Scale (CIRS). 

Addition of either rituxan or GA-101 thumped chlorambucil doubling the overall response rate from 30 to 60-70%.  Complete response rate with chlorambucil came in with a whopping 0%, adding rituxan took it to 8%, and GA-101 got it to 22%.  While the increased response rate was encouraging you could say that was the same in the other study listed above that wasn't quite as exciting.

The key to this being something really new was that the progression free survival went from 10 months with chlorambucil to 15 months with rituxan and 23 months with GA-101.  To me that indicates that GA-101 is really doing something new / better than the stalwart rituximab.  Infusion reactions were a bit more significant with GA-101.

For a variety of statistical considerations they did not directly compare the rituxan group to the GA-101 but looking at the raw numbers things look good for GA-101.  In fact Genentech looks pretty happy with the data and sounds like the drug has been labeled "breakthrough drug" with the FDA indicating a fast track for approval in near future!

GA-101 has been circling around under the radar for a little while.  While the stories of patients on the new B Cell receptor inhibitors have been very exciting, I don't think there was quite the buzz out there for this drug.  I love it when we get a nice surprise!