Another delay with new platelet drug

[Wendy Beltrami]

Amgen media release from last week:


http://www.amgen.com/media/media_pr_...easeID=1127316

[Birgitta-A]

Hi Wendy,
Since I read an abstract about Nplate and MDS where 2 of 40 patients got AML and 6 other patients got increased blast cells I stopped waiting for Nplate because I dare not take it. Now I am waiting for the next drug for thrombocytopenia called Eltrombopag/Promacta/Revolade. That drug is perhaps better for patients with bonemarrow diseases - Nplate is maybe OK for patients with idiopathic thrombocytopenic purpura (a autoimmune disease).
Kind regards
Birgitta-A
last platelet count 49

[Wendy Beltrami]

Birgitta,
Well, that certainly is a concern. If it keeps getting delayed, perhaps Promacta and Nplate will end up being available at about the same time.

Can you send me the link to that abstract? Promacta/Revolade is actually more attractive since it is oral anyhow.

Are you anticipating that it will be out in 2008 as well?

Wendy B.

[Birgitta-A]

Hi Wendy,
This abstract is from ASH 2007. Eltrombopag could be approved by FDA June 2008 - GlaxoSmithKline applied for approval Dec 2007.

"Phase 1/2 Study of AMG 531 in Thrombocytopenic Patients (pts) with Low-Risk Myelodysplastic Syndrome (MDS)

Hagop Kantarjian, Pierre Fenaux, Mikkael A. Sekeres, Pamela Becker, Adam Boruchov, David Bowen, Richard Larson, Roger Lyons, Petra Muus, Jamile Shammo, Michael Ehrman, Kuolung Hu, Janet Nichol MD Anderson Cancer Center, Houston, TX, USA; Hopital Avicenne Universite Paris XIII, Bobigny, France; Cleveland Clinic Taussig Cancer Center, Cleveland, OH, USA; Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Leeds Teaching Hospitals, Leeds, United Kingdom; University of Chicago, Chicago, IL, USA; Cancer Care Centers South Texas/US Oncology, San Antonio, TX, USA; Radboud University Medical Centre, Nijmegen, Netherlands; Rush University Medical Center, Chicago, IL, USA; Amgen Inc., Thousand Oaks, CA, USA

Background: AMG 531 is a novel thrombopoiesis-stimulating peptibody that is being studied for its ability to increase platelet production by stimulating the thrombopoietin receptor.

This report updates outcomes in Part A of the study as of May 2007 on pts who continued into the extension phase of this ongoing phase 1/2, open-label, sequential-cohort, dose-escalation study to evaluate the safety and efficacy of AMG 531 in low risk MDS pts with severe thrombocytopenia.

Methods: Pts with low- risk MDS (IPSS Low or Intermediate-1, excluding CMML), a mean baseline platelet count 50x109/L, and only receiving supportive care were eligible to enter this study.

Pts were enrolled into sequential cohorts of 300, 700, 1000, and 1500g, receiving 3 weekly subcutaneous injections of AMG 531. After evaluation of platelet response at week 4, pts could continue AMG 531 in an optional treatment extension at their assigned dose or dose adjust to achieve or maintain a response.

Results: The mean duration of exposure to AMG 531 was 23.155 (SD) weeks. Of 44 pts enrolled, 40 continued into the extension phase; 16 pts remain on treatment. Eighteen pts (41%) achieved a durable platelet response (per IWG 2006 criteria for at least 8 consecutive weeks).

Evaluation of durable responses based on baseline platelet count showed that responses occurred in 12/29 (41%) pts with a baseline count of 20x109/L, and in 6/15 (40%) pts with a baseline count of <20x109/L.

The mean duration of the platelet response was 22.813 (SD) weeks. A total of 104 platelet transfusions were given to 17/44 (39%) pts during this study; of these transfusions, 7 were given in 3/18 (17%) pts who achieved a durable response.

Treatment-related AEs were reported in 17 pts. There were 3 deaths unrelated to treatment. Two confirmed cases of transformation to AML were reported. These two pts received maximum doses of 300 and 1000g.

Six pts were confirmed to have temporary blast cell increases, three of whom had increases above 20%. Of the 6, 4 were receiving 1500g and 2 were receiving 1000g. In all 6 pts, blast cell counts were observed to have fallen upon follow-up assessments within 7 weeks after treatment discontinuation. In one case, treatment was reinitiated at 700g.

Conclusions: In this study, AMG 531 appeared to be well-tolerated () in severely thrombocytopenic low-risk MDS pts, and resulted in increased and sustained platelet counts in the responding pts. AMG 531 may have a role in the treatment of low-risk MDS pts who are thrombocytopenic or have a history of bleeding. These data suggest that further exploration is merited in this pt population. Pt recruitment is ongoing until reaching the planned 84 pts."
Kind regards
Birgitta-A

[george peveto]

I took 300 mg of Amgen 531 back in 2007
after 4 weeks the blast cells in my blood went up to around 5% and in the bone marrow I was near 20%
we stopped the injections and after 30 days the blast returned to normal (below 5%) in the marrow.
Started on 100 mg injections and again after two weeks the blast went up to 5 % so we discontinued the injections ----- the stuff worked great on Platelets though as my platlet count increased from the 27,000 range to around 50,000 and if I could have continued i suspect they would have gone up even more
have a good week
george.peveto@verizon.net

[Birgitta-A]

Hi George,
You know both Nplate and Promacta/Revolade are approved but have restrictions so only patients with Immune Thrombocytopenic Purpura can get the drugs so far.
The FDA has a special warning about Nplate in MDS patients because the drug can make you disease worse (page 12) : http://www.fda.gov/cder/foi/label/2008/125268lbl.pdf
Promacta/Eltrombopag seems to decrease leukemia cells in tubes. A new drug LGD 4665 should be in trials for MDS and many other drugs for low platelets are in pipelines .
Kind regards
Birgitta-A