Thursday, May 2, 2013

ABT-199 is Coming Back

ABT-199 is soon coming back to trial near you and this could be very good news.

News release from AbbVie (formerly part of Abbott):

ABT-199, our next-generation BcL-2 inhibitor in development in partnership with Roche/Genentech, was featured in a special symposium at the American Association for Cancer Research (AACR) annual meeting earlier this month. AbbVie recently proposed an amended study protocol for ABT-199 in chronic lymphocytic leukemia. Upon approval by the U.S. Food and Drug Administration (FDA), dose escalation and new patient recruitment will resume.


Much tighter monitoring, immediate sharing of adverse data between sites, and slower dose escalation  done in an inpatient setting, are my guesses as to what will be part of the restart. 

As I have discussed before over a few posts, the best way to kill a good drug is to rush it to market. 

A patient told me this trial may reopen as soon as June. Here's hoping.

ABT-199 offers very powerful disease reduction, but at the risk of potentially fatal tumor lysis syndrome or TLS where the cancer is killed so effectively and so fast that the kidneys and other organs can't cope with the toxic waste produced. This has been seen in flavoperidol (where there is required pre-emptive care), lenalidomide, and other CLL drugs. It can usually be handled with careful monitoring and appropriate aggressive medical intervention including dialysis for the worse patients, and should be preventable for the majority with cautious dose escalation and meticulous monitoring.

Blocking BcL-2 as discussed in my prior posts with Dr. Tom Kipps, is an attractive target in CLL and a logical piece of a intriguing future non-chemo cocktail in combination with something such as idelalisib or ibrutinib that might offer outstanding durable disease control.

I am glad ABT-199 is coming back.

Finally, our celebration of this possible important new arrow in our CLL quiver with forever be tinged with sadness over the loss of the two brave volunteers who died in the trial from TLS. I won't diminish their sacrifice by saying that it allowed this progress. No, instead I simply suggest that we need to insist on trials that are well designed to maximize benefit and minimize risk. Truth is most are, but we are dealing with so many unknowns. Adverse events and even deaths are never fully preventable, and it is too easy be critical in hindsight. After all we are talking about experimental therapies (see post by Dr. Furman on Phase I trials) but we need to constantly remind the researchers that bring us these new options to always put safety ahead of expediency. That may be no fun us lab rats either, perhaps slowing the time it takes until we get to the dose where we respond and maybe even demanding that we are admitted to hospital overnight, but such is the cost of progress.

In trials using multiple sites, bad news must travel fast to ensure necessary adjustments are systemic and near instantaneous.

Even with all these precautions, there will always be risks, so I forever laud the brave subjects who without whom there would be no progress. 

My readers know me to be strongly pro clinical trials. For many of us, the risk of the trial is less than the risk of traditional therapy or doing nothing. I still feel that way, and still encourage everyone to consider  an appropriate clinical trial.

All I am saying is let us do what we can to minimize all our risks.

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4 Comments:

Anonymous Anonymous said...

Brian, Thank you for the information
Yes, Looking forward to the combination of these new drugs one day (in the future) will be the next big exciting 'breakthrough'. Hopefully the trial of ABT-199 will be back on soon. Erik

May 2, 2013 at 3:46 PM  
Anonymous Anonymous said...

Brian check some spelling please :) like formerly instead of formally. And actually AbbVie is not former Abbot, it is just partially as Abbott still exist, this was a split.

with Flavopiridol the management of TLS was too cruel and I think this was one of the reason the drug didn't get anywhere. It was also not too robust anyway.

With ABT199 hospitalization overnite was already in the protocol. I guess there will be carefull monitoring. I doubt they would put VazCath in patients like it was with me in Flavopiridol trial.

Greg Z

May 4, 2013 at 2:36 PM  
Blogger Brian Koffman said...

Greg,
Thanks for the careful and thoughtful reading.
I made the corrections
Be well
Brian

May 5, 2013 at 12:09 AM  
Anonymous Anonymous said...

Brian,

Just had my 15 month abt199 trial check up. All is well and steady. Trial will likely begin in June/July. Beginning at 20 mg vs. 50mg. Hospitalization for EACH increase in medication. 600mg is highest dose they are giving. All patients currently in the trial continue to do well...cll and lymphoma. The focus of this drug may shift to a maintenance drug. That was the latest discussion this month.

Stay well.

Wendy

May 8, 2013 at 6:42 AM  

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