Romiplostim Study Results Announced

[Wendy Beltrami]

Just wanted to be sure everyone saw this news that came out this week:


http://www.amgen.com/media/media_pr_...easeID=1085803


We're hoping to get our hands on this drug as soon as it is approved. Evidently the trials using it with MDS have been promising as well.

Wendy/mom to Grant
dx 12/4/98 AA

[Birgitta-A]

Hi Wendy,
I have been waiting for AMG 531/Romiplostim/Nplate since I got my dx May 2006 but since I read an abstract about Romiplostim in MDS patients from ASH 2007 I am waiting for next drug for platelets Eltrombopag/Promacta/Revolade. Here is the abstract:

"Phase 1/2 Study of AMG 531 in Thrombocytopenic Patients (pts) with Low-Risk Myelodysplastic Syndrome (MDS): Update Including Extended Treatment.

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 2315.5 (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 22.813.3 (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
68 yo, MDS Interm-1 dx May 2006, transfusion dependent, Desferal 4 days every 5th week, Neupogen 2 injections/week

[Wendy Beltrami]

Birgitta-
If Grant had MDS we would already be trying it. Waiting for Eltrombopag could mean waiting many months more and time is not on our side. To my uneducated eye, it appears that the higher doses of Romiplostim are the ones related to more adverse events. ANY increase in platelet count that would get Grant off of platelet transfusions would be GOLDEN for us.

Everything we have ever tried with this disease has had risk and yes, I understand your concerns. The state he is in currently appears to have been triggered by the mycophenolate that we tried back at the end of 2005. It always has been and always will be a matter of considering whether the next treatment will improve his health or add new problems which is why we are still NOT choosing transplant at this point.

Wendy/mom to Grant
dx 12/4/98 AA

[Birgitta-A]

Hi Wendy,
Yes, I understand that your situation will make you try the first drug - AMG 531/Romiplostim/Nplate. Amgen filed to FDA Oct 2007. There are at least 6 more drugs coming up the pipelines for low platelets .

Number 2 in the race is Eltrombopag/Promacta/Revolade and Glaxo/Smith/Kline has promised to file to FDA Dec 2007. Eltrombopag seems to inhibit leukemia cells in cell culture tests .
Kind regards
Birgitta