Or I heard it wrong?
Eight presentations with belinostat. Most important is 3075 "Safe and Effective Treatment of Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma (PTCL) and Low Baseline Platelet Counts with Belinostat"
Conclusions: Complete and partial responses were seen with belinostat overall and in the subgroup of patients with low baseline platelet counts. Patients with baseline platelet counts less than 100,000/µL tolerated belinostat at a high dose intensity that was similar to that of patients with baseline platelet counts higher than 100,000/µL, did not experience a higher proportion of AEs, and benefited from belinostat treatment. Thus, belinostat is suitable for use in patients with R/R PTCL and low baseline platelet counts, and may also be useful in developing new treatment regimens in combination with other cytotoxic agents.
There are five Zevalin presentations at ASH this year. From one of them:
3986 Minimum Tolerable Interval of Radioimmunotherapy and Autologous Stem Cell Transplantation after High-Dose Chemotherapy for Relapsed or Refractory Aggressive B Cell Non-Hodgkin-Lymphoma Provides Excellent Disease Control
Background: Patients with aggressive B cell Non-Hodgkin-Lymphoma failing from immune-chemotherapy show disappointing results with standard salvage therapies and consolidation of high-dose chemotherapy with autologous stem cell transplantation. Especially in cases never in remission or with early relapse outcome is poor. Several groups started trials combining high-dose chemotherapy of carmustin, etoposide, cytarabine and melphalan (BEAM) with 90Yttrium ibritumomab tiuxetan to enhance the efficacy of the preparative regimen. In this trial we tested safety, feasibility and studied efficacy of reduced intervals of 90Yttrium ibritumomab tiuxetan to autologous stem cell transplantation after BEAM.
Conclusions: 90Yttrium ibritumomab tiuxetan and BEAM followed by autologous stem cell transplantation was safe and feasible. The minimum tolerable interval of 90Yttrium ibritumomab tiuxetan and autologous stem cell transplantation is 10 days. With shorter intervals of radioimmunotherapy and high-dose chemotherapy and therefore more concomitant therapy, we did not observed excessive toxicity, but enhanced disease control of refractory or relapsed aggressive B-NHL. Our results compare favorable to standard BEAM or allogeneic stem cell transplantation. A formal comparison in a phase III trial is warranted.
Forgot about posting rules, continue
The median cumulative dose of VLIP group (10.09mg/m2) was nearly double the median cumulative dose of VCR group (5.42mg/m2) (p less than 0.001). Since identical dose reduction rules were applied, we expected equal neurotoxic effects with VLIP and VCR, which was indeed the case. Before initiation of therapy 100% of patients receiving VCR showed PNP grade 0 while 15.2% of patients in the VLIP-group showed PNP grade 1 (84.8% grade 0) which was significantly worse (p=0.018). After cycles 1 and 2 the median grade of polyneuropathy was 0 in both groups, which increased to a median toxicity of grade 1 after cycles 3, 4, 5 and 6. The maximum grades of polyneuropathy observed in both groups were not significantly different (p=0.865). In the VLIP group no liposomal vincristine was administered in 18 patients (34.62%) , in the VCR arm group no vincristine in 14 patients (26.42%) in at least one cycle of therapy (p=0.361). Due to polyneuropathy no VLIP was given in 16 patients (30.77%), no VCR in 12 patients (22.64%) for the minimum of one cycle of therapy (p=0.346).
Conclusions: With nearly twice the dose of VLIP achieved in elderly patients treated in the OPTIMAL 60 study, the preset goals were met and the study will continue as planned. A total recruitment of 864 patients is necessary to demonstrate whether the double dose of VLIP will translate into a significantly improved outcome in 3-year PFS (HR 0.68 or 9% with an alpha=5% and a power of 80%). Acknowledgement: This study was supported by Spectrum, Amgen and Roche.
4420 Liposomal Formulation of Vincristine Allows for Doubling the Dose Compared to Conventional Vincristine: Results of the First Futility Analysis of the OPTIMAL 60 Study of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL)
Results: In this planned futility analysis of the OPTIMAL 60 trial, we investigated the cumulative dose of liposomal (VLIP, Marqibo®) and conventional vincristine (VCR) and the neurotoxic effect of the first 105 patients. Fifty-three patients received VCR and 52 patients VLIP. In comparing the median cumulative dose received for each group. The median cumulative dose of VLIP group (10.09mg/m2) was nearly double the median cumulative dose of VCR group (5.42mg/m2) (p 60 study, the preset goals were met and the study will continue as planned. A total recruitment of 864 patients is necessary to demonstrate whether the double dose of VLIP will translate into a significantly improved outcome in 3-year PFS
1. 3dQ results
2. ASH abstracts publication. New data on Belinostat, Marqibo, Folotyn, Zevalin.
3. CE-Melphalan NDA submission.
First two will happen on November 6 for sure. Third one has a good chance to be delivered on same date too.
Hope, Spectrum is in a much better situation. Not even close to what is going on with Sarepta.
"But the FDA statement, which the agency issued to mollify parents of DMD patients, suggests Sarepta executives may have misunderstood some of the key issues that agency staffers discussed with the drug maker, notably the timing for submitting trial data and concerns about FRAUD at a clinical trial site."
Something is wrong about Sarepta's data. I do not believe that monitoring dystrophin expression is a difficult task. And why did they terminated Arthur Krieg, a recently hired CSO?
-In addition, the FDA has called into question the technique Sarepta has used to show that eteplirsen has helped patients produce more dystrophin—the protein that Duchenne patients lack. Garabedian said that the FDA uncovered “marked disparities” in that methodology and has “concerns about the reproducibility of the data.” As a result, it now wants that data to be independently assessed. Sarepta also now has to have a 168-week set of clinical data from the 12-patient study in hand at the time of the NDA submission, as opposed to submitting it while the FDA is already reviewing the application.
"The FDA wanted to CRL rhpt1-84 but because of the orphan status instead applied heavy REMS and a 3 month delay." Sounds like you are working for FDA. Is it insider information?
Searched "PDUFA Extension" on Google. Here are the first 10 drugs mentioned.
I decided on 10, I didn't peek forward to see what 11 or 15 or 20 would bring.
All these drugs received a 3-month extension
Revlimid - Approved
Trametinib - Approved
Qnexa - Approved
Xiaflex - Approved
Takligucrase alfa - Approved
Uceris - Approved
Melblez - CRL
Feraheme - Approved
Benlysta - Approved
Rytary - CRL
So - an 80% approval rate after 3-month delay from my quick, statistically under-powered search.
It is not my analysis. I tried to provide a reference but it was blocked earlier today.
It can happen anytime. For example, on May 1, 2013 FDA extended Trametinib PDUFA date by 3 months to September 3, 2013. Guess when it was approved? On May 29, 2013.
Their phase 3 study was not designed to measure QOL. Primary outcome measure in trial was reduction of calcium and vitamin D supplements. Paper that I mentioned was published after BLA submission. Study described in paper was designed to measure QOL.
"Where are the Clinical Numbers to show QOL?" As I already posted, read the article "PTH(1–84) Is Associated with Improved Quality of Life in Hypoparathyroidism Through 5 Years of Therapy". Believe me, your numbers are there.
It is open label study. Data should have been monitored since the beginning of the trial. Company already knows the outcome. Guess, nothing to be exited about.
You need to read an article "PTH(1–84) Is Associated with Improved Quality of Life in Hypoparathyroidism Through 5 Years of Therapy" published in J Clin Endocrinol Metab this year.
Conclusions: PTH(1–84) therapy is not only associated with improvement in biochemical and skeletal
indices, previously well-documented, but also in mental and physical health as determined by
the SF-36 metric.