Stem Cell Transplant

March 6, 2017

Merck & Co. issued results of a phase III study of letermovir for the prevention of clinically significant cytomegalovirus (CMV) infection in adult (18 years and older) CMV-seropositive recipients of an allogeneic hematopoietic stem cell transplant (HSCT), also known as bone marrow transplant (BMT). CMV seropositive HSCT recipients who had undetectable plasma CMV DNA within five days of randomization were eligible for the study. Patients were randomized in a 2:1 ratio to receive either letermovir or placebo administered once daily, either in oral tablet or intravenous formulation, through week 14 (day 100) post-HSCT. Letermovir was dosed at 480mg/day (or 240mg/day if the patient was on the immunosuppressant medication cyclosporine). Letermovir was started after HSCT, as early as the day of transplant and no later than 28 days post-transplant. The study met its primary efficacy endpoint, showing that of 495 treated patients who had undetectable CMV DNA at the start of study treatment, significantly fewer patients developed clinically significant CMV infection in the letermovir arm (37.5%, n=122/325) compared to the placebo arm (60.6%, n=103/170) through week 24 post-HSCT [treatment difference: -23.5 (95% confidence interval -32.5 to -14.6), one-sided p<0.0001]. In addition, a secondary endpoint evaluating the end-of-treatment period (at week 14 post-HSCT) showed that significantly fewer patients developed clinically significant CMV infection in the letermovir arm (19.1%, n=62/325) compared to the placebo arm (50.0%, n=85/170) through week 14 (day 100) post-HSCT [treatment difference: -31.3 (95% confidence interval -39.9 to -22.6), one-sided p<0.0001]. In this study, letermovir was associated with lower all-cause mortality through week 24 post-HSCT (9.8%, n=32/325) compared to placebo (15.9%, n=27/170), log-rank two-sided p=0.0317. The company will submit regulatory applications for letermovir in 2017. 

April 16, 2012

Neuralstem reported interim results from a phase I trial evaluating spinal cord stem cells for the treatment of Amyotrophic Lateral Sclerosis. The trial plans to enroll 18 subjects with varying degrees of the disease. The first stage of the trial enrolled 12 subjects received five-to-ten stem cell injections in the lumbar area of the spinal cord. Of the 12 subjects, the first six (cohort 1) were non-ambulatory and the second six (cohort 2) were ambulatory. The subjects were examined at regular intervals post-surgery. At 18 months post-transplant none of the subjects experienced any long-term complications related to either the surgical procedure or the implantation of stem cells, or showed signs of rejecting the cells. In the months following the surgery to inject the cells, none of the subjects showed evidence that their ALS progression was accelerating. The FDA has granted approval for the trial to advance to the final two groups of subjects, all of who will be transplanted in the cervical region of the spinal cord.

February 13, 2012

Chimerix issued results from a phase II trial of CMX001 for the prevention of cytomegalovirus (CMV) disease in hematopoietic stem cell transplant (HCT) recipients. This randomized, double-blind, placebo-controlled, dose-escalation study (Study 201) enrolled 230 CMV seropositive allogeneic stem cell transplant recipients. Following engraftment, subjects were stratified based on the presence or absence of acute GVHD and CMV DNA in plasma. They were then placed into five sequential, dose-escalating cohorts and were treated once or twice weekly for 9 to 11 weeks through post-transplant Week 13. Results from subjects receiving CMX001 100 mg twice weekly met the primary endpoint, a statistically significant reduction in CMV viremia (CMV>200 copies/mL) or disease at the end of treatment versus those who received placebo (p≡0.001). Three different doses of CMX001 demonstrated statistically significant reductions in the proportion of subjects with CMV viremia>1000 copies/mL at any time during treatment when compared to placebo (p≡0.002, <0.001, <0.001, respectively). In subjects who were CMV viremia negative prior to treatment, four different CMX001 dose regimens (100 mg and 200 mg once weekly and twice weekly) demonstrated statistically significant reduction versus placebo.

February 16, 2009

ViroPharma released negative results from a phase III trial of maribavir for the prevention of cytomegalovirus (CMV) disease in recipients of allogeneic stem cell transplants. This randomized, double-blind, placebo-controlled, multi-center study enrolled 500 subjects who had undergone allogeneic stem cell transplantation. Following transplantation, subjects were randomized to receive maribavir (100mg twice daily) or matching placebo for a maximum duration of 12 weeks. They were to undergo testing for CMV infection at least once a week. The primary efficacy endpoint was the incidence of CMV disease within 180 days post-transplant. Secondary endpoints included incidence of initiation of preemptive anti-CMV therapy, incidence of graft-versus-host disease, mortality and CMV disease-free survival. The primary endpoint was not reached; there was no statistically significant difference between maribavir and placebo in reducing the rate of CMV disease. In addition, the study failed to reach the secondary endpoints. The incidence of CMV disease within 6 months was 4.4% for maribavir compared to 4.8% for placebo (p≡0.79). The rate of initiation of anti-CMV treatment within six months, which was 37.9% for maribavir compared to 40.5% for placebo (P≡0.49). In addition, the incidence of graft-versus-host disease, mortality and CMV disease-free survival was comparable between the groups.

July 30, 2007

Genzyme reported positive results from a phase III trial of Mozobil as an agent for increasing the number of hematopoietic stem cells collected for a transplant. This randomized, double-blind, placebo-controlled trial enrolled 298 subjects undergoing a hematopoietic stem cell transplant (HSCT) for non-Hodgkin's lymphoma, in the US and Canada. The trial was designed to compare the hematopoietic stem cell yield from subjects treated with Mozobil in combination with granulocyte-colony stimulating factor (G-CSF, standard of care) to subjects treated with G-CSF in combination with placebo. The primary efficacy endpoint was achieved, with 59% of the subjects in the Mozobil arm reaching the target threshold for collection of at least 5 million CD34+cells/kg from the peripheral blood with four or fewer days of apheresis sessions, compared with 20% in the placebo arm (p=0.0001). The secondary endpoint also reached statistical significance, with nearly 87% of the subjects in the Mozobil arm minimum level of stem cells generally associated with a successful transplant (2 million CD34+cells/kg) in four or fewer days of apheresis sessions, compared to 47% in the placebo arm (p<0.0001). Genzyme plans to file for US and European approval for lymphoma in the first half of 2008.

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