I just received the 12/10/14 issue of Oncology Times, which contains an article by Dr. Robert Carlson on "Chronic Myelogenous Leukemia(CML):Urgent Call to Focus on Improving Compliance". In the real world, as opposed to closely monitored studies, patient's often forget to take meds, particularly when they are supposed to be taken on full stomach and more then once a day. GILD's drug has a decided advantage in this case, which may well translate in to a lower overall cost due to failure to achieve cure with the more complicated ABBV regimen.
There are several continuing medical education and related on line sites that always publish "the Best of..." after any major medical meeting in which they describe the half dozen or so major events, and this is true for ASH 2014 as well. Virtually all of the ones I have seen mention Valor as one of the high lights of ASH 2014..
CYCC tanked 75% this morning after the ph3 negative data on sapacytabine was released.To the best of my knowledge, no other AML drug under development is close to FDA submission.
NEJM is the gold standard of medical journals. I was told that the initial response from the Journal was" favorable". If the study is published in the Journal, it would be a significant validation of Valor. Keeping fingers crossed
Monday, December 08, 2014
ONLINE FIRST: Quinolone Derivative Vosaroxin Active in Relapsed/Refractory AML
BY ROBERT H. CARLSON
SAN FRANCISCO--Vosaroxin, a quinolone derivative tested in a trial of 711 patients with relapsed/refractory acute myelogenous leukemia (AML) in combination with cytarabine, produced higher complete response rates and overall response rates by stratified log rank analysis than cytarabine plus placebo.
The trial, called VALOR, which will be presented here at the American Society of Hematology Annual Meeting on Tuesday, also showed equivalent 30- and 60-day survival times for the two study arms (Abstract LBA 6).
Speaking at a news conference on Sunday, Farhad Ravandi, MD, Professor and Chief of the Section of Developmental Therapeutics in the Department of Leukemia at the University of Texas MD Anderson Cancer Center, reported that the median overall survival was 7.5 months for vosaroxin versus 6.1 months for the control group.
Complete response (CR) rates were 30.1 percent for vosaroxin-cytarabine versus 16.3 percent for cytarabine-placebo.
The improvement in median overall survival, though, for patients on the combination arm who did not have a subsequent allogeneic stem cell transplant--6.7 months versus 5.3 months for the control arm—was not statistically significantly different. The p value is 0.06.
But when stratified by age, median overall survival with vosaroxin-cytarabine for patients age 60 and older was statistically significantly better, at 7.1 months for vosaroxin-cytarabine versus 5.0 months for the controls.
And when outcomes were stratified by age and by allogeneic stem cell transplant status, the results showed a statistically significantly improvement with vosaroxin, with a p value of 0.02.
“Vosaroxin should be considered as a new standard of care for relapsed/refractory AML, particularly in older patients,” Ravandi said.
The trial was funded by Sunesis, the drug’s manufacturer, which announced that based on t
Just by chance I watched a continuing medical education session by Dr. David Steensma, to whom Feurstein attributed very negative comments. This is NOT the case in the CME program, which I invite you to watch. Steensma acknowledges that Valor was a big study and came pretty close to statistical significance, and if you sensor out the patients who had bone marrow transplant, it did achieve significance! He regards the study as a baby step forward, Steemsa says nothing about the drug not being a candidate for approval
Saturday's Best of the Day from the 2014 Annual Hematology Meeting in San Francisco
Imedex is pleased to present Best of the DaySM from the 2014 Annual Hematology Meeting. This daily update is brought to you direct from the meeting in San Francisco, California, USA..
In today’s online streaming video program, I am joined by Drs. Srdan Verstovsek and David P. Steensma to explore the most clinically relevant, new, and updated data presented in today's sessions. The topics will include Myeloproliferative Neoplasms, Myelodysplastic Syndromes, Acute Lymphocytic Leukemia, and Acute Myeloid Leukemia.
If you have a mobile device:
Srdan Verstovsek, MD, PhD
View mobile version
Myelodysplastic Syndromes, ALL, and AML
David P. Steensma, MD
View mobile version
I attended a wonderful symposium on "New Territory in Acute Leukemia" this afternoon. Speakers included Drs.Ravandi, Erba, Schlenk and Strickland. The Valor study was presented(along with many others). There was considerable enthusiasm for IDAC and vosaroxin for patients 60 year old. There is NO question that this sub-group had been identified and statified at the start of the study, so this is NOT a retrospective look back to find a group that did well. Dr. Erba mentioned that VOR had particular efficacy in patients who had early relapse, a most challenging group. It offers these patients the possibility of being re-induced into remission, and then being candidates for allogeneic bone marrow transplant. It was also mentioned that the IDAC control group had similar efficacy to other salvage regimens. Hence, the Valor study did not simply look good because of suboptimal results in the control group. Although the overall study (barely) failed to reach statistical significance for OS, they thought it would be a shame if FDA failed to approve VOR for 60 year olds. I feel increasingly optimistic regarding SNSS
There has been much criticism the study(the control arm was not intensive enough, sub-group analysis was not "previously" announced, etc). I have reviewed the analyst reports from 2012 and 2013(Credit Suisse.Wedbush,Leerink,RBC, Cantor Fitz and Cowen) and there was NO criticism by the analysts at that time. I am citing below the input upon which the Valor study was based and it seems pretty impressive to me:
The Steering Committee will provide scientific oversight for the VALOR trial as well as communicate its recommendations regarding trial conduct with the trial's Data Safety Monitoring Board and Sunesis. Steering Committee members are:
-- Eric Feldman, MD, Chair of Steering Committee, Professor of Medicine
and Director of the Leukemia Program and Hematological Malignancies at
Weill Cornell Medical College
-- Harry Erba, MD, PhD, Associate Professor, Department of Internal
Medicine at the University of Michigan and Executive Officer of the
Southwest Oncology Group
-- Gary Schiller, MD, Professor of Medicine, Director of the Hemapherisis
Unit and Chairman of the Medical Specialties College of the David
Geffen School of Medicine at the University of California, Los Angeles
-- Robert Stuart, MD, founding director of the Aplastic Anemia &
Myelodysplastic Syndrome Foundation, Director of the clinical
component of the Hollings Cancer Center's Hematological Malignancies
Program and Medical Director of the Clinical Trials Office at the
University of South Carolina
-- Norbert Vey, MD, Professor of Medicine, Leukemia and MDS Unit,
Department of Hematology at the Institut Paoli-Calmettes, Marseille,
Among the clinical trial partners appointed by Sunesis are (i) ICON, a contract research organization with global capabilities, hematology expertise and extensive Phase 3 experience; (ii) Catalent Pharma Solutions, a leading global provider of advanced technologies, and development, clinical, manufacturing and package
We will learn the details at the Late Breaking Abstract session next Tuesday afternoon, as well as the audience
opinion in the Q and A that follows the presentation
PRE-DEFINED sub group analysis is perfectly legitimate. VOR is far from the definitive drug for AML, but clearly has efficacy in the relapsed/refractory AML group 60 yr. I see no reason why FDA would not grant approval for this group. Elderly relapsed/refractory AML is a particularly challenging group, and even a modest, incremental benefit is worthwhile. VOR/CYT had NO greater toxicity then VOR/PLA. KOL in heme/onc appear to have favorable opinion that VOR should be added to the armamentarium.
I am impressed that SNSS is sponsoring a continuing medical education symposium at the ASH meeting. This is usually the domain of big pharma. Vosaroxin will undoubtedly be discussed:
On behalf of the course director, Farhad Ravandi, MD, we thank you for your registration for “New Territory in Acute Leukemia: How Cutting-Edge Science and Novel Therapies Will Change Patient Care.”
This educational symposium is CME-accredited by Penn State College of Medicine and CNE-accredited by the Institute for Advancement of Human Behavior. Please visit www.peerviewpress.com/AML for additional details.
Friday, December 5, 2014
12:30 – 1:00 PM PST: Registration and Lunch
1:00 – 3:00 PM PST: Symposium
Meeting Room: 2001/2003
I think the oral presentation at the special" Late Breaking Abstracts Session" is a big deal. It emphasizes the significance of the data regarding vosaroxiin and it is presented to a large audience..The data will likely be updated to 12/1/14. It will provide validation of the sub group analysis demonstrating the efficacy of the drug.
Sapa may work for MDS, but little hope of efficacy for AML. The CEO of CYCC is rumored to be a tyrant and the progress towards FDA approval has been exceedingly slow
no idea.I was certainly frustrated! I resubmitted the post a few hours later, and as you will see, it is now in conventional English
I doubt the bar needs to be lowered! Vosaroxin demonstrated significant improvement of OS(overall survival), for a couple of sub groups and barely missed OS for the overall study. OS is the most challenging outcome; most FDA approvals are based on less meaningful PFS(progression free survival). The secondary end points such as remission rate were also excellent. The low toxicity of vosaroxin is also a big +.Vosaroxin's approval willl not simply be approval of another drug in a competitive area(so often the case today), but the first new drug for AML in two decades based on a clever mechanism of action.
I am a retired hematologist, having practiced at the MGH for 40 years. There has been no new drug for the treatment of acute myelogenous leukemia in over 20 years. It is a terrible disease and improved treatment is desperately needed. The information on vosaroxin detailed in the Late Breaking Abstract for the annual meeting of the American Society of Hematology released on 11/17 is quite compelling, and its authors are key opinion leaders in the field of leukemia research. The fact that the abstract was one of only six selected for this Late Breaking designation further supports the significance of the results. I anticipate a good deal of favorable press when the abstract is presented on 12/9. The fact that vosaroxin has orphan drug status both from the FDA as well as the European Drug Agency makes an expedited approval highly likely. The fact that vosaroxin has efficacy in relapsed/refractory patients, the most challenging type of AML patient, makes it quite likely that it will also have efficacy as upfront therapy. This is currently in a phase 2 investigator sponsored trial. It is also likely that the drug will have efficacy in the related condition, myelodysplastic syndrome, which is also in a phase 2 investigator sponsored trial. Vosaroxin could easily have sales greater than $1 billion per year, yet SNSS only has a market cap of 130 million. I am strongly long, and I think anyone who is currently shorting the stock is making a big mistake
Sentiment: Strong Buy
destined to h#$%$ve much more widespre#$%$d use. There #$%$re #$%$ huge number of #$%$bstr#$%$cts which will be presented #$%$t the Annu#$%$l Meeting of the Americ#$%$n Society of Hem#$%$tology, 12/6-12/9. I #$%$nticip#$%$te #$%$ lot of f#$%$vor#$%$ble publicity