"The FDA is also currently reviewing Vanda's application for three years marketing exclusivity based upon the REPRIEVE study submission and subsequent PI changes and expansion now approved in the sNDA."
Most important part of announcement.
Spectrum Pharmaceuticals' wholly owned subsidiary Allos Therapeutics settles its patent litigation with Teva Pharmaceuticals USA related to lymphoma drug Folotyn (pralatrexate injection). The settlement allows Teva to market a generic version of Folotyn in the U.S. on December 1, 2022 or earlier under certain circumstances.
Allos' litigation with other would-be generic competitors continues.
I think Spectrum is also not interested in starting new trials with Folotyn. Composition of matter patent covering Folotyn is due to expire in 2022. Before that, they need to win a case against Folotyn ANDA in a trial which starts on September 12, 2016.
Celgene is not running active studies with Istodax as a lead sponsor. The reason for that, I think, is a patent expiration in 2021. One phase 3 trial with Istodax, Ro-CHOP in PTCL, is run by The Lymphoma Academic Research Organisation. They have a primary completion date as of July 2019.
First, it is not my opinion. I provided a reference for this info which I think is interesting. Second, median duration of response in Folotyn trial was 10.1 months. It means, that for responders, median cost of treatment is higher than $300,000. And third, I don't see it as something negative or positive for Spectrum.
It is number 7. Cost $320,000 a year
Yes, it seems like Folotyn is even more effective in CTCL than in PTCL, "Response or disease stabilization (CR, PR, SD) were seen in 21 of 27 pts with CTCL and 4 of 7 with PTCL". I like the data. No matter what disease it is, CTCL or PTCL, leucovorin almost completely eliminates mucositis caused by Folotyn.
Two pts with CTCL and one with PTCL discontinued therapy before response assessment due to intolerability or pt withdrawal. Conclusions: Addition of Leuc significantly reduced the incidence of mucositis in pts with PTCL and CTCL but interestingly did not change the incidence of skin reactions, suggesting alternative mechanisms of the drug to induce skin rash in these patients. Response rates were similar in the Pral-Leuc group and the Pral group, suggesting no impact of Leucovorin on clinical efficacy.
Comparison of hospital costs in peripheral t-cell lymphoma patients treated with pralatrexate or romidepsin.
Background: Peripheral T-Cell Lymphoma (PTCL) is a rare, aggressive form of non-hodgkin lymphoma. Initial treatment consists of conventional chemotherapy regimens; although novel therapies for relapsed/refractory patients are available there is a lack of information on real-world costs associated with these products. The objective of this study was to examine costs and healthcare resource use associated with two of these novel products, romidepsin and pralatrexate. Methods: A retrospective analysis examined costs in PTCL patients treated with pralatrexate- (n = 50) and romidepsin-based (n = 59) regimens in a nationally representative MedAssets hospital-based administrative claims dataset covering inpatient and outpatient services. Costs were collected during the time patients were considered to be on therapy and were standardized into cost per day. Between group differences were tested using analysis of variance and multivariable general linear regression Results: On average, pralatrexate patients had higher average total costs per day of therapy compared to romidepsin patients [$1,459 (SD: $1,502) vs $975 (SD: $759) p less than 0.05]. Both treatment regimens had similar mean number of inpatient admissions (0.50 vs 0.46 p = 0.83) and length of stay (3.94 vs 3.31 days p = 0.68). Comparison of adverse events showed significantly higher rates of anemia (18.5% vs 6.3% p = 0.04) and infections (13% vs 3.1% p = 0.04) for pralatrexate patients compared to romidepsin. In a regression analysis, patients using pralatrexate based regimens had a 69% higher costs of $717 per day (IRR 1.69 p less than 0.05) after controlling for differences in patient characteristics and lines of therapy
Impact of leucovorin on mucositis and skin reactions in pts with peripheral t-cell lymphoma (PTCL) and cutaneous t-cell lymphoma (CTCL) treated with pralatrexate.
Background: Pralatrexate (Pral,) is a novel folic acid analog with activity in T cell lymphomas. In the clinical trial of Pral in relapsed PTCL, treatment modification occurred frequently due to mucositis, and/or skin reactions. Leucovorin (Leuc) administration has been shown to minimize mucositis without sacrificing efficacy in patients (pts) with PTCL (Haddad, 2011), and CTCL pts (Koch, 2013).The aim of this study was to define the potential clinical benefits of Leuc with Pral on frequency of mucositis and skin reactions in pts with relapsed/refractory PTCL and CTCL Methods: A retrospective review of consecutive pts treated with Pral was conducted. Pts either received Pral or Pral-Leuc with Leuc given at a dose of 50 mg orally q 6 h x 4 doses the day following Pral. All patients treated before 2013 received Pral without Leucovorin and those treated after 2013 received Pral-Leuc. Thirty-four pts (17 female, 17 males) were identified, including 7 with PTCL (6 stage IV, 1 stage III) and 27 with CTCL (11 Stage IIB, 9 Stage IV). The age range was 27-89 years (median 54 years). Results: Pral dosing ranged from 10-30 mg/m2 weekly x 3 q28 days or every q other week. In the Pral group (n = 24), 46% (n = 11) of pts reported mucositis and 48% (n = 10) had skin reactions.Three pts who had initiated therapy only with Pral and developed mucositis were then given Leuc on subsequent cycles and mouth sores did not recur, In the Pral-Leuc group (n = 10), one pt had mucositis. The incidence of skin reactions was the same for Pral and Pral-Leuc. Response or disease stabilization (CR, PR, SD) were seen in 21 of 27 pts with CTCL and 4 of 7 with PTCL. The mean number of cycles of Pralatrexate was 7 (range 2-18).
Development of novel backbones for the treatment of peripheral T-cell lymphoma (PTCL): The pralatrexate/romidepsin doublet.
Background: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of lymphomas in which only 20-25% of patients
experience long-term survival with CHOP chemotherapy. Recently several drugs have been approved for this entity including pralatrexate (P), romidepsin (R), and belinostat which have response rates ranging from 26%-29% as single agents. Based on our demonstration of synergy of P+R in preclinical models of TCL, we initiated a study on the safety and efficacy of P+R in a phase I-II study for relapsed or refractory lymphomas (NCT01947140). Methods: A 3+3 dose-escalation study started at P 10mg/m2 and R 12mg/m2 with escalation to P 25 mg/m2 and R 14 mg/m2. Patients were treated on 1 of 3 dosing schedules (weekly x 3 Q28D; weekly x 2 Q21D and QOW Q28D). The primary objective was to determine MTD and DLT; the secondary objective included describing ORR (CR+PR). Patients were required to have relapsed lymphoma of any subtype, ECOG PS less than 2, and adequate organ and marrow function. There was no upper limit to the number of prior therapies or transplantation. Results: Twenty-five patients were enrolled and were evaluable for toxicity. Median age was 52 yrs (23-73) and 60% were male. The median number of prior therapies was 3 (range 1-16). Histologies included HL (N = 3), B-cell (N = 7 of which FL = 4) and T-cell (N = 15). The median number of cycles completed was 4 (range 1-8+ ongoing). There were 3 DLTs in cohort 4 (P 20mg/m2& R 12mg/m2given weekly x 2 Q21D) consisting of 2 Grade 3 oral mucositis and 1 Grade 4 sepsis. The QOW Q28D schedule had no DLTs at equivalent and higher doses.
SPI-1620 disappeared from Spectrum home page completely. It is not present under "Product Development", "Out-Licensing Opportunities" or any other places. Good luck in waiting for positive data from SPI-1620 studies.
We examined the efficacy of poziotinib, a second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) in patients with lung adenocarcinoma with activating EGFR mutations, who developed acquired resistance (AR) to EGFR-TKIs.
Materials and Methods
This single-arm phase II study included EGFR-mutant lung adenocarcinoma with AR to erlotinib or gefitinib based on the Jackman criteria. Patients received poziotinib 16 mg orally once daily in a 28-day cycle. The primary endpoint was progression-free survival (PFS). Prestudy tumor biopsies and blood samples were obtained to determine resistance mechanisms.
Thirty-nine patients were treated. Tumor genotyping was determined in 37 patients; 19 EGFR T790M mutations and two PIK3CA mutations were detected in the prestudy tumors, and seven T790M mutations were detected in the plasma assay. Three (8%; 95% confidence interval [CI], 2–21%) and 17 (44%; 95% CI, 28–60%) patients had partial response and stable disease, respectively. The median PFS and overall survival were 2.7 (95% CI, 1.8–3.7) months and 15.0 (95% CI, 9.5–not estimable) months, respectively. A longer PFS was observed for patients without T790M or PIK3CA mutations in tumor or plasma compared to those with these mutations (5.5 vs. 1.8 months, p=0.003). The most frequent grade 3 adverse events were rash (59%), mucosal inflammation (26%), and stomatitis (18%). Most patients required one (n=15) or two (n=15) dose reductions.
Low activity of poziotinib was detected in patients with EGFR-mutant NSCLC who developed AR to gefitinib or erlotinib, potentially because of severe-toxicity-imposed dose limitation.
"A Phase II Study of Poziotinib in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Lung Adenocarcinoma who Have Acquired Resistance to EGFR-Tyrosine Kinase Inhibitors" in Cancer Research and Treatment · May 2016
Nothing new on efficacy but there is important data on adverse events. The incidence of grade 3 diarrhea was 10%. Neratinib causes grade 3 diarrhea in one third of patients. Although supportive care including anti-diarrhea medication was allowed in Poziotinib study.
has changed from "recruiting" to "active, not recruiting" and AZN enrolled 400 patients, instead of 304, as planned.
In Europe, a different chemo regimen for breast cancer is used. Spectrum planned to run two trials, one for US and one for European approval. They gave up European development.
This article describes several hypoxia activated prodrugs including Apaziquone . There you can find a short history of Apaz development, which is not long enough for entire lecture. I would like to hear about the mechanism of Apaz inactivation by blood.