January 23, 2017
Keryx Biopharmaceuticals reported results of a phase III study of ferric citrate for iron deficiency anemia (IDA) in non-dialysis-dependent chronic kidney disease (NDD-CKD). The pivotal study randomized 234 patients (233 patients received at least one starting dose of ferric citrate) at 32 clinical sites in the U.S. NDD-CKD patients with hemoglobin levels between 9g/dL and
11.5g/dL and who were intolerant to or had inadequate response to oral iron supplements were randomized 1:1 (ferric citrate versus placebo), n=117 and n=116, respectively. Patients enrolled in the study were not allowed to receive any IV or oral iron, or ESAs during this study. The study had a 16-week, randomized, double-blind, placebo-controlled efficacy period followed by an eight-week open-label safety extension period in which all patients remaining in the study, including the placebo group, received ferric citrate. During the 16-week efficacy period, ferric citrate was administered at a starting dose of three tablets per day with food and could be titrated every four weeks by an additional three tablets for up to a maximum of 12 tablets per day; the mean dose received in ferric citrate treated patients was five tablets per day. The primary endpoint was the proportion of patients achieving a =1g/dL increase in hemoglobin at any point during the 16-week efficacy period. Baseline laboratory values were similar between the treatment arms. Use of ferric citrate in patients with NDD-CKD and IDA, as highlighted above, is investigational and has not been determined to be safe or efficacious. Ferric citrate delivered a clinically meaningful 1g/dL increase in hemoglobin levels for the majority (52.1% (61/117)) of patients treated at any point during the 16-week efficacy period, increases were seen as early as one to two weeks after start of treatment and were sustained for the majority of patients who achieved the primary endpoint. Ferric citrate was generally well-tolerated and adverse events were consistent with its known safety profile, with diarrhea reported as the most common adverse event.
August 1, 2016
Janssen-Cilag International announced results from an international phase III, randomized, double-blind, placebo-controlled, multicenter study of EPREX (epoetin alfa) for anemia in adult patients with low or intermediate-1 risk myelodysplastic syndromes (MDS). Results demonstrated that 31.8% of patients treated with epoetin alfa achieved the primary endpoint of erythroid response versus 4.4% of placebo patients (p<0.001). An ad hoc analysis, accounting for the dose adjustments as per the protocol, confirmed a statistically significant erythroid response for epoetin alfa, with 45.9% of epoetin alfa patients, versus 4.4% of placebo patients achieving an erythroid response (p<0.001). Median erythroid response duration for epoetin alfa patients was 197 days. The number of patients needing transfusion in the epoetin alfa arm steadily decreased from 51.8% in the eight weeks prior to baseline, to 24.7% by week 24. Transfusion need remained unchanged in the placebo patients (48.9% to 54.1%) over the same interval. Time to first transfusion was longer in the epoetin alfa group (p=0.046). Epoetin alfa demonstrated a statistically significant improvement of quality of life in responding patients. These data, along with three registry studies from across Europe, have been submitted to the French health authority Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM).
February 16, 2015
Emmaus Life Sciences released results of a
phase III study of oral pharmaceutical grade
L-glutamine (PGLG) treatment for sickle cell
anemia and sickle beta-0 thalassemia. The
multi-center, double-blind clinical trial studied
PGLG for sickle cell disease (SCD) in 230 pediatric
patients as young as five years old and adults.
Study participants were randomized to receive
daily PGLG (152 patients) or placebo (78 patients)
for 48 weeks, after which treatment levels
were tapered to zero. Researchers observed
patients who received PGLG experienced fewer
painful crises (three v. four events during the
study period, a 25% reduction) and a longer
time to a pain crisis than patients receiving
placebo. Treated patients also were less likely to
be hospitalized (two v. three events during the
study period, a 33% reduction) and spent less
time in the hospital for these events (6.5 v. 11
days, a 41% reduction) than those receiving placebo.
The percentage of patients experiencing
acute chest syndrome, a severe complication of
SCD, was less than half among the PGLG group
as compared to the placebo group (11.9% v.
26.9%, or 58% fewer cases). The therapy has
Orphan Drug designation in the U.S. and Europe
and Fast Track designation from the FDA.
March 21, 2011
Incyte and Novartis released results from a phase III trial of ruxolitinib for the treatment of myelofibrosis. This randomized, open label trial, COMFORT-II (COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Therapy), enrolled 219 subjects across Europe. The subjects received ruxolitinib at doses titrating from 5 mg to 25 mg twice daily or best available care. The primary endpoint, the proportion of subjects achieving at least 35% reduction in spleen volume from baseline to Week 48, was reached with significance. The safety profile was consistent with previous studies.
November 1, 2010
Alexion issued positive interim results from two phase II trials of eculizumab for the treatment of atypical Hemolytic Uremic Syndrome. The first open label trial enrolled 17 adolescent and adult subjects who were resistant to plasma therapy. The subjects received eculizumab for up to 26 weeks. The primary endpoint of the study is the change in platelet count, a measure of thrombotic microangiopathy (TMA). Data showed a significant increase in platelet count with eculizumab treatment compared to baseline (p<0.0001). Key secondary clinical endpoints were also positive. The second open label trial enrolled 20 adolescent and adult subjects who were receiving plasma therapy chronically prior to entering the study. The primary endpoint was TMA Event-Free Status, as defined by stable platelet counts, absence of plasma therapy and no new dialysis. In this interim analysis of 15 subjects treated with eculizumab for at least 12 weeks, a significant 87% achieved the primary endpoint. Key secondary clinical endpoints were also positive. Eculizumab was well-tolerated, with the most common adverse events including anemia, diarrhea, headache, nausea and hypertension.
October 11, 2010
Akebia reported positive results from a phase IIa trial of AKB-6548 for the treatment of anemia due to chronic kidney disease. This U.S-based, open label trial enrolled 22 subjects with stage 3 and 4 chronic kidney disease. The subjects received a single, oral dose of AKB-6548 and erythropoietin (EPO) levels were measured at eight, 12 and 24 hours post-administration. AKB-6548 resulted in significantly increased EPO levels eight and 12 hours post administration, with levels returning to baseline within 24 hours, supporting the potential of once daily dosing. The compound was found to be safe, with no serious adverse events.
June 21, 2010
Akebia issued positive results from a phase Ib trial of AKB-6548 for the treatment of anemia. This multi-dose study enrolled 33 healthy subjects who received three ascending doses of AKB-6548 once daily for 10 days. AKB-6548 increased in erythropoietin and reticulocytes and there were no serious adverse events at any of the doses tested.
May 18, 2009
Lipoxan issued positive results from a phase I trial of ErepoXen for the treatment of anemia in cancer and renal disease patients. This randomized, double-blind, placebo-controlled single dose study enrolled 64 healthy male subjects in India. The subjects who received ErepoXen were assigned to four dose cohorts: 0.5, 1.5, 3.0 and 4.5 micrograms/kg. The primary endpoints were the safety, pharmacokinetics and pharmacodynamics of ErepoXen. The pharmacodynamic data showed that ErepoXen exerts a dose-dependent increase in reticulocyte count. This increase was particularly prominent in the subjects receiving the two higher doses of ErepoXen, with maximum reticulocyte count reached seven days after dosing. The reticulocyte counts then took between 14 and 20 days to return to baseline values, suggesting a long-acting effect on erythropoiesis. In addition, subjects receiving ErepoXen also saw an increase in hemoglobin levels when compared to baseline and these effects lasted up to 28 days after dosing. ErepoXen was well tolerated and no safety issues were reported.
April 16, 2007
Affymax released positive results from a phase II trial of Hematide for the treatment of anemia in dialysis patients. This open-label, multi-dose study enrolled 165 subjects undergoing hemodialysis with stable baseline Hgb levels between 10 and 12.5 g/dL on previous Epoetin Alfa therapy. The trial was designed to evaluate hemoglobin (Hgb) and reticulocyte levels, Hematide dose adjustments, red blood cell transfusions and safety of switching from the three times weekly regimen of Epoetin Alfa to the once monthly regimen of Hematide. Results revealed that mean Hgb levels were maintained at clinically acceptable levels after the switch to Hematide. Of the 90 subjects who had completed six months of treatment, mean reticulocyte increases were observed after every Hematide injection. The mean Hgb level, which was 11.5 g/dL at baseline, was maintained within +/- 1 g/dL at the end of six months of treatment. Treatment was well tolerated in all the subjects. Based on the results, Affymax is undergoing discussions with the FDA regarding the phase III trial design.
June 19, 2006
Alexion Pharmaceuticals has announced positive interim results of a phase III trial, dubbed SHEPHERD of Soliris (eculizumab) for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). 6-month data met their primary surrogate efficacy endpoint, significantly reducing median lactate dehydrogenase levels (a biomarker for intravascular hemolysis) by 87%, from 2051 U/l at baseline to 270 U/l at 26 weeks (p<<0.00000000001). Significance was also achieved in all pre-specified secondary endpoints, including reduction in mean LDH change from baseline and quality of life as measured by the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-Fatigue) diagnostic measure. The most frequent adverse events associated with Soliris treatment were headache, nasopharyngitis, and nausea. This open-label study enrolled 97 PNH patients across 33 sites in the US, Canada, Europe and Australia, who were to receive treatment with the drug for 12 months.
November 21, 2005
Roche issued positive results of a phase II extension study of CERA for the treatment of anemia in chronic kidney disease (CKD) patients not yet on dialysis. Weekly (11.3 g/dL), once-every-two-weeks (11.4g/dL) and once- every-three week (11.7 g/dL) doses of the drug met their primary efficacy endpoint of maintaining hemoglobin levels between 11 and 12 g/dL throughout the treatment period. The drug was generally well tolerated: the most frequently reported adverse events were urinary tract infections, gout, hypertension, peripheral edema, and insomnia. This open-label study enrolled 51CKD patients, who received treatment with subcutaneous doses of CERA once weekly, once every 2 weeks or once every 3 weeks for 54 weeks.
June 13, 2005
Affymax announced positive results of a phase I trial of Hematide, their peptide- based erythropoiesis stimulating agent under investigation for the treatment of anemia in patients with chronic kidney disease (CKD) and cancer. The results were presented at the European Hematology Association meeting in Stockholm. Data produced a met safety endpoints, with no serious adverse events reported and a positive overall tolerability profile. Dose-dependent erythropoietic activity was observed, including increased in circulating reticulocytes. The highest trial dose also produced a statistically significant increase in hemoglobin levels from baseline, which were maintained through one month. This open-label, proof-of-concept study enrolled healthy volunteers, who received single ascending doses of Hematide.
Roche reported positive results of a phase II study of their investigational anti-anemic agent CERA (Continuous Erythropoietin Receptor Activator), at the European Renal Association—European Dialysis and Transplant Association congress in Istanbul. Trial data indicated that the drug produced consistent hemoglobin levels independent of frequency of administration; specifically, dosing once every 4 weeks produced hemoglobin levels of 11.15 g/dL, dosing once every 3 weeks produced levels of 11.18 g/dL, and once weekly dosing achieved levels of 11.33 g/dL. 61 anemic patients on dialysis received one of the three dosing schedules of CERA for 12 months in this randomized, multicenter, dose-ranging study. The company announced that there data would serve to support their ongoing phase III trials of the drug in the treatment of anemia related to CKD, and NDA filing in 2006.
March 14, 2005
Affymax has issued positive results of a phase I trial of Hematide, their synthetic peptide-based erythropoiesis stimulating agent under investigation for the stimulation of red blood cell production in patients with anemia due to chronic kidney disease and cancer. Primary safety endpoints were met, with no serious adverse events reported and a tolerability profile similar to placebo. Pharmacokinetic/pharmacodynamic data yielded preliminary evidence of efficacy, with single ascending doses resulting in dose-dependent increases in circulating reticulocyte levels and the highest dose level producing a statistically significant increase in sustained (1 month) hemoglobin levels. This placebo-controlled, dose-escalation study enrolled healthy volunteers into one of 4 dosing cohorts, which received single ascending doses of the drug or placebo, followed by observation for 1 month. Following these results, the company announced plans to initiate phase II trials of the drug later in 2005.
ProMetic Life Sciences issued additional positive results of a phase I trial of PBI-1402, for the treatment of anemia. Results from extended data analysis indicate that the drug produced a statistically significant increase in the number of circulating reticulocytes, vs. placebo at day 21 (p<0.0001). The drug also yielded an increase in the number of burst-forming unit-erythroid cells, precursors to reticulocytes. This randomized, double-blind, dose-escalating, placebo-controlled study enrolled 5 cohorts of 8 healthy volunteers each, who were randomized to receive PBI-1402 or placebo via oral dose for 21 days. The company announced plans to extend this trial into 2 higher dosing cohorts, and to extend the duration of treatment for healthy volunteers, as well as a new trial enrolling anemic patients undergoing chemotherapy.<
February 7, 2005
Angiogenix reported negative efficacy results from a phase II trial of Acclaim (isosorbide mononitrate plus L-arginine), for the prevention of nitrate tolerance in patients with chronic stable angina. The trial failed to meet its primary efficacy endpoint, a statistically significant increase in treadmill walking time following treatment. The trial also failed to meet secondary endpoints, though positive, non-significant trends were observed for time to onset of angina, ST-segment depression, and improvement seen with concomitant ACE inhibitor therapy. Trial data did meet their primary safety endpoint, with acceptable profiles for both incidence of serious adverse events and tolerability. This randomized, double-blinded, placebo-controlled, multi-center study enrolled 204 subjects across 7 countries. The company announced plans to continue the development of Acclaim, with a re-assessment of dosing data based on these results prior to future studies.
December 13, 2004
BioCryst Pharmaceuticals announced additional data from both phase I and phase I/II clinical trials of forodesine hydrochloride, their investigational Purine Nucleoside Phosphorylase (PNP) Inhibitor for the treatment of several types of leukemia and lymphoma. Results from the phase I study demonstrated pharmacokinetic activity, with a near-total inhibition of PNP at a dose of 40 mg/m2. Evidence of efficacy in treating subjects with cutaneous T-cell lymphoma was also observed, with 9 out of 13 patients showing improvement in skin and/or a pharmacodynamic response (including 3 complete responses and 1 partial response). Furthermore, two patients who received forodesine continued to show evidence of clinical activity through 9 -11. Results from the phase I/II study indicated that the drug was well-tolerated in all patients at all dose levels. 7 of the 15 patients treated demonstrated a decrease in tumor burden, and 2 patients also showed normalization of bone marrow precursor elements. Both studies were multi-center dose-escalating trials; the phase I study enrolled 13 subjects with cutaneous T-cell lymphoma, and the phase I/II study enrolled 15 subjects with mixed hematological malignancies. Based on these results, BioCryst recently initiated a phase I trial in CTCL patients using an oral formulation of forodesine.
Bristol-Myers Squibb reported results of a phase I trial of BMS-354825, for the treatment of chronic myelogenous leukemia (CML). Results from the study demonstrated significant efficacy in treating chronic, accelerated and blast-phase CML: 86% of the chronic phase patients demonstrated complete hematologic response, and 75% and 79% of the accelerated and blast phase patient groups demonstrated some degree of hematologic response. Cytogenetic responses were observed in 28%, 0%, and 53% of patients, respectively. This ongoing, open-label study has enrolled a total of 65 subjects with imatinib-resistant or –intolerant Philadelphia chromosome positive CML at a single US site. The company has announced the intention to initiate phase II development as soon as possible, following successful completion of this trial.
Celgene announced final results from a phase III trial investigating their approved drug Thalomid (thalidomide) for the treatment of multiple myeloma. Results from the study indicate that the addition of Thalomid to standard dexamethasone therapy produced a statistically significant increase in response rate at 4 months, vs. dexamethasone alone (63% vs. 41%; p=0.002). Median time to response was similar for both regimens, at 1.1 months. Subjects receiving Thalomid did experience a significant increase in adverse events, consistent with the drug’s well-established tolerability profile. Deep vein thrombosis was the most frequent of these events. This double blind, controlled trial randomized 207 patients with previously untreated symptomatic multiple myeloma to receive Thalomid (n=103) or placebo (n=104) in addition to standard therapy with dexamethasone. The study was designed to investigate both response and toxicity. Based upon these results, Celgene announced plans to submit a request during Q1, 2005 for accelerated approval of their sNDA for Thalomid for the treatment of multiple myeloma.
Cell Genesys reported positive follow-up data from a phase II trial of their GVAX leukemia vaccine, for the treatment of acute myelogenous leukemia (AML). Data from the ongoing extension study have indicated that the drug is well tolerated, and may reduce residual leukemic cells that persist after chemotherapy. Specifically, post-vaccination declines in levels of WT-1 (a genetic marker of leukemia), were observed in blood samples of 69% of patients (11 of 16) and in 60% (12 of 20) of patients’ bone marrow samples. Furthermore, relapse-free survival was greater in the patients who showed a decrease in WT-1 levels following vaccination, compared to those who did not (80% vs. 0%, p=0.02 for blood, 90% vs. 20%, p=0.002 for bone marrow). This open-label study enrolled 54 AML patients across 4 US leukemia bone marrow transplant centers, who received autologous bone marrow stem cell transplantation and GVAX leukemia vaccine treatment following successful response to chemotherapy.
FibroGen reported results from both phase I and IIa trials of FG-2216, their investigational oral treatment for anemia. Results from the phase I study met their primary safety and tolerability endpoints, with no serious adverse events or dose-limiting toxicities. The trial also characterized the drug’s pharmacokinetic profile, noting a dose-dependent increase in serum levels of erythropoietin (EPO), a hormone which stimulates red blood cell production. Repeated doses maintained EPO elevation, which lead to a consistent increase in the number of circulating reticulocytes (young read blood cells) after three weeks of dosing. Preliminary data from the first dosing cohort (n=8) from the ongoing phase IIa study indicated that patients receiving FG-2216 experienced a increases in mean hemoglobin levels from baseline, while subjects who received placebo experienced a mean decrease; the difference between the FG-2216 and placebo groups was statistically significant at both 3 (p = 0.024) and 6 (p=0.025) weeks. The open-label phase I trial enrolled 54 healthy male volunteers, who received dose-escalating single or multiple doses of the drug for up to 3 weeks. The phase IIa trial is one of several ongoing single-blind, placebo controlled studies designed to evaluate the safety and efficacy of FG-2216 in anemic patients suffering from chronic kidney disease, including both EPO naïve and EPO experienced individuals.
Icagen announced positive results of a phase II study of ICA-17043, for the treatment of sickle-cell anemia. Trial data met their primary efficacy endpoints, with a dose-dependent increase in hemoglobin level from baseline; this increase was statistically significant for the high-dose treatment group (p<0.001). Secondary efficacy measures were also achieved, including increases in hematocrit and red blood cell counts, and statistically significant improvements in dense red blood cells, reticulocyte count, LDH, and indirect bilirubin. These improvements suggest that the drug reduces hemolysis and improves anemic symptoms in patients with sickle cell anemia. This randomized, double-blind, placebo-controlled, dose-range-finding study enrolled 90 patients with sickle cell anemia across 19 academic medical centers in the US, who received one of two daily doing regimens (6 or 10 mg) or placebo. It was designed to establish the efficacy of the drug in producing a change in hemoglobin level from baseline.
Novartis issued mixed results of a phase III trial of ICL670, an orally-available once-daily iron chelator, for the treatment of chronic hyperferremia (iron overload). The two high-dose regimens of the drug achieved their primary endpoint of maintaining or reducing absolute liver iron concentration (LIC), producing a highly significant reduction of -5.3 plus or minus 8.0 mg Fe/g dry weight (P<0.001), compared to baseline. This reduction was non-inferior to the reduction produced by standard therapy with deferoxamine. The two lower dose of ICL670, however, did not demonstrate non-inferiority, meaning that the overall endpoint of non-inferiority to deferoxamine for all doses was not met. The international, open-label, randomized, multicenter Phase III study enrolled 586 patients with beta-thalassemia and transfusion-related iron overload, who were randomized to receive once daily ICL670 at one of four doses (5, 10, 20 or 30 mg/kg) or deferoxamine (20-60 mg/kg/day for 5 days/week). Based on these results, Novartis announced that they anticipated filing regulatory submissions with a number of international bodies for ICL670 in the first half of 2005.
Nuvelo issued positive results of a phase II trial of alfimeprase, their recombinant thrombolytic enzyme under investigation for its potential to restore function in patient’s occluded central venous access devices (CVADs). The highest trial dose demonstrated significant efficacy in improving catheter patency, with total patency rates of 50% at 15 minutes after the first dose, 60% at 120 minutes after the first dose, and 80% at 120 minutes after the second dose, compared to rates of 0%, 46%, and 62% among patients receiving approved therapy with Cathflo Activase. This randomized, double-blind, active-controlled, dose-ranging study compared the safety and efficacy of three doses of alfimeprase (0.3 mg; 1.0 mg; and 3.0 mg) against an approved dose of Cathflo Activase (2.0 mg), enrolling 55 patients with occluded CVADs. Catheter patency was assessed at 5, 15, 30, and 120 minutes after each dose, with subsequent doses administered only if patency was not achieved after the first.
December 6, 2004
Penwest Pharmaceuticals announced mixed results from a pivotal phase III study of low doses of its investigational beta blocker PW2101, for the treatment of hypertension and angina. Trial data failed to meet their primary efficacy endpoint, with a non-significant change in Mean Seated Office Cuff diastolic blood pressure from baseline to week six, compared to placebo (2.4 mmHg, p>0.05). The trial did meet secondary endpoints, including a significant increase in 24-hour Mean Ambulatory diastolic blood pressure from baseline to week six, compared with placebo. A previous phase III pivotal trial of low-dose PW2101 also produced significant evidence of efficacy. This randomized, double-blind, placebo-controlled study enrolled 110 hypertensive patients, who received low dose low-dose PW2101 or placebo for 6 weeks. The company announced plans to submit these data to the FDA as an expansion of the PW2101 NDA, which is currently under review, in hopes of broadening the dosing indications for the drug.
June 7, 2004
Hoffmann-La Roche reported positive results from a phase II trial investigating CERA (Continuous Erythropoiesis Receptor Activator) for the treatment of anemia. Results demonstrated that CERA maintained stable control of hemoglobin levels in 80% of subjects with chronic renal anemia receiving dialysis. The study enrolled 91 subjects with chronic renal anemia who were receiving hemodialysis. Subjects received CERA intravenously once every two weeks and had been previously treated with intravenous epoetin three times weekly. Final results were reported at the 2004 European Dialysis and Transplant Association (EDTA) meeting.