Tuesday, May 21, 2013

Inotuzumab sinks....

Inotuzumab flops in DLBCL

I am very excited about a new class of investigational therapies called "antibody drug conjugates (AKA. ADC's".(see my prior post on these fascinating drugs).  In essence these are "smart bombs" compared to old school chemotherapy that goes after just about everything. 

An ADC is an antibody loaded up with powerful chemotherapy.  Once infused, the expectation is that the antibody will help deliver the chemotherapy directly to the tumor cells sparing healthy tissue.

Scientists have been playing with this concept for many years.  In fact Paul Ehrlich initially proposed the idea in the late 1800's before we even knew that antibodies existed (visionary!).

The first drug ADC approved was myelotarg for acute myeloid leukemia (a much more aggressive disease than CLL/NHL).  Unfortunately, the drug had some significant side effects including liver damage and the drug was pulled off the market although recent studies may bring the drug back to life.

The team at Seattle Genetics extensively studied the science of how to use an antibody to deliver chemotherapy specifically to cancer cells and came up with brentuximab.  This has been a quantum leap in the management of Hodgkin's lymphoma.  Once the science of the linker and chemotherapy was solved - solving a new disease was simplified to finding the right surface marker on the cancer cells.  That is a science that is pretty advanced in CLL/NHL and now a host of companies are developing drugs in these diseases.

Genentech just got another such drug approved in breast cancer called traztuzumab-emtansine (T-DM1).  This is a big step forward in patients with breast cancer and a particular marker on the surface of the cancer cells.

Meanwhile, Pfizer (who made myelotarg) continued development using the "myelotarg technology" but turned their attention on B cell cancers.    Inotuzumab used a different antibody but the same drug and "glue" (the linker that attaches the drug to the antibody).  The drug looks very active in acute lymphoblastic leukemia and development continued in DLBCL.  Unfortunately - in a press release out today it looks like the drug failed to improve outcomes sufficient to justify continuing the trial.

We are fortunate however that a number of companies have seen the success of brentuximab and are looking to make their mark on B cell cancers.  I can think of about a half dozen drugs that are being studied in NHL. While inotuzumab didn't pan out, I think it used the most primitive technology out there.  The remainder of the research drugs out there use the 2.0 technology (smarter linker / drug).  It will be exciting to see how these influence outcome!