Valor's data barely missed statistical significance for the entire study BUT were stunning in the pre-defined sub-set of patients 60 and in those with short remissions. The FDA appears to have set a precedent with the NVS drug just approved for multiple myeloma in approval based on a sub-set group. Hence, things look more favorable for FDA approval for vosaroxin based on its sub-set success.
The FDA just approved Novartis" new drug for multiple myeloma on basis of sub-groupp analysis:
The US Food and Drug Administration (FDA) today granted accelerated approval to panobinostat (Farydak, Novartis) for the treatment of patients with relapsed multiple myeloma.
Late last year, panobinostat was voted down at an FDA Oncologic Drugs Advisory Committee meeting that had considered its use in relapsed multiple myeloma. The agency said that after that meeting the company submitted additional information supporting the agent's use for a slightly different indication, and it was this that was approved.
The approval is for use of the panobinostat in patients with relapsed multiple myeloma who have received at least two prior standard therapies, including bortezomib (Velcade, Millennium) and an immunomodulatory agent. This is an area of unmet medical need, the company noted.
Panobinostat is approved for use in combination with bortezomib and dexamethasone.
The drug is a first in a new class of agents that act as inhibitors of histone deacetylases.
"Panobinostat has a new mechanism of action that distinguishes it from prior drugs approved to treat multiple myeloma, making it a potentially attractive candidate agent," said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, in a statement. This FDA approval is based on efficacy and safety data in a prespecified subgroup analysis of 193 patients who had received prior treatment with both bortezomib and an immunomodulatory agent. This subgroup of patients participated in the phase 3, randomized, double-blind, placebo-controlled, multicenter global registration trial, known as PANORAMA-1 (PANobinostat ORAl in Multiple MyelomA).
The findings showed that, in this subgroup, the median progression-free survival in patients treated with panobinostat was higher than that in the placebo arm (10.6 months, n = 94 vs 5.8 months, n = 99; hazard ra
Dear Dr. Ellman,
You heard correct that one of our patients in our PK trial received 21 cycles of aldoxorubicin. The dose was 230mg/m2 (170mg/m2 doxorubicin equivalents) and the small cell lung cancer patient had progressed following platinum plus etoposide.
VP, Business Development & Investor Relations
This certainly bodes well for the ph3 study where aldox is given until dz progression vs. fixed amount of dox.
Steensma invited Ravandi to comment, who responded that he thinks of AML as being equivalent to metastatic cancer: “Patients with relapsed AML present with disease all over their body from day one. In solid tumors we are excited about a one- or two-month improvement in survival; I don't see why we shouldn't be excited about that in AML as well,” he said.“And we have set the bar high for ourselves in AML with about 40 percent of patients cured. You don't see 40 percent cure in metastatic cancers. This improvement in AML is highly significant—we should not discount the small steps forward in treating our patients and providing them better treatment options.”Asked for her perspective for this article, Anjali Advani, MD, Director of the In-Patient Leukemia Unit and Associate Professor at Cleveland Clinic Lerner College of Medicine, said it is encouraging to see responses like this in such a poor-risk population.Still, she said it is important to keep in mind that the dosing of cytarabine used in VALOR was lower than that typically used for salvage in relapse-refractory AML. “However, this modified dosing was likely used to be able to encompass an older population,” she noted.Advani called the results encouraging: “This is a poor-risk population, and they did include older patients.”One question is whether the responses would have been better in the standard arm with a higher dose of cytarabine, particularly for younger patients, she added. “What would have happened to the experimental arm in that setting?”Patients in the trial were stratified between the two arms for allogeneic transplant, which was not mandated, Advani noted. “For patients who ultimately relapse, even though they can get back into remission with more chemotherapy, that remission is not going to be durable without an allogeneic bone hematopoietic stem cell transplant.”
This is a monthly journal sent to hematologists and oncologists monthly:
SAN FRANCISCO — Mark R. Litzow, MD, professor of medicine at Mayo Clinic and chair of the ECOG-ACRIN Leukemia Committee, highlights data demonstrating that combination therapy with vosaroxin and cytarabine was associated with longer OS in patients with acute myeloid leukemia.
Litzow noted that the phase 3 double-blind randomized controlled VALOR study showed benefit of survival in patients with first-relapsed or refractory AML who received vosaroxin.
According to study results, median OS was 7.5 months for vosaroxin compared with 6.1 months for placebo, with a complete response rate of 30.1% for vosaroxin vs. 16.3% for placebo.
“I think this drug did show benefit and I think it adds a potential new agent to our treatment of patients who are in a very difficult situation with relapsed or refractory AML,” Litzow told HemOnc Today. “Whether this will ultimately get approved by the FDA, we’ll need to see, but I think the results are favorable enough that it should be given serious enough consideration.”
but what if SAFM beats on earnings? I would think there is opportunity fr a big pop. With feed prices down, it is quite possible for a beat.
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.