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September 23, 2013
Rockwell Medical issued results of a phase III study of SFP for the treatment of iron deficiency in chronic kidney disease patients receiving hemodialysis. The single-blind, placebo-controlled, parallel-group study comparing SFP (2μM [110μg iron/L] delivered via hemodialysate concentrate) to placebo (standard hemodialysate concentrate) consisted of three stages: run-in, randomization and open-label extension. Patients who continued to meet inclusion criteria during the run-in period were randomized 1:1 to receive either SFP via dialysate or placebo (standard dialysate) in a blinded manner for up to 48 weeks. The study successfully met its pre-defined primary efficacy endpoint. The mean difference between SFP and placebo was 3.6g/L (95% CI 0.8, 6.3) in favor of SFP, and was statistically significant (p=0.011). At baseline the two groups had similar hemoglobin levels (109.6g/L SFP and 109.3g/L placebo). The mean adjusted change from baseline hemoglobin to the end of the randomized treatment period in the SFP group was -0.5g/L (95% CI -2.6, 1.7). In placebo, there was a statistically significant decline of -4.0g/L (95% CI -6.2, -1.9). This study is the second and final of two identical phase III efficacy studies to provide clinical data required to file an NDA.
February 4, 2013
Keryx Biopharmaceuticals released results from a long-term, phase III trial of Zerenex (ferric citrate) for the treatment of hyperphosphatemia (elevated serum phosphorus levels). This randomized, open-label, active-controlled study enrolled 441 patients with hyperphosphatemia and end-stage renal disease (ESRD) who were on hemodialysis or peritoneal dialysis. Subjects underwent a two-week washout period and then received either a 1g oral caplet of Zerenex or an active control (Renvela and/or Phoslo) for 52 weeks. Subjects were titrated during the study to achieve serum phosphorus levels that ranged between 3.5mg/dL to 5.5mg/dL. Data demonstrated Zerenex met the primary efficacy endpoint of mean change in serum phosphorus from baseline with a highly statistically significant result (p<0.0001). Baseline at week 52 was 5.2 for Zerenex and 5.3 for placebo, whereas at the end of treatment, Zerenex had a baseline of 4.9 (-0.3) and placebo had a baseline of 7.2 (1.9). In addition, as agreed to with the EMA, Zerenex successfully achieved the non-inferiority endpoint versus Renvela. Zenerex was well tolerated. This long-term study was the final component of Keryx Biopharmaceuticals’ phase III registration program, which was conducted pursuant to a Special Protocol Assessment with the FDA. Keryx expects to submit a New Drug Application with the FDA and a Marketing Authorization Application with the EMA for Zerenex in the second quarter of 2013.
January 28, 2013
Spectrum Pharmaceuticals reported results from a phase I trial of RenaZorb for the treatment of hyperphosphatemia. This double-blind, dose-ranging study enrolled 32 patients with hyperphosphatemia and stage five chronic kidney disease (CKD). Subjects were divided into four sequential dose cohorts and received RenaZorb 1500mg, 3000mg, 4500mg or 6000mg daily, split into three doses each, or placebo. Results showed RenaZorb was well-tolerated up to the maximum administered dose of 6000mg. RenaZorb-treated subjects also showed statistically significant reductions in daily urinary phosphorous excretions at all four dose levels compared to placebo. RenaZorb showed no serious adverse events, low systemic exposure and no discontinuations of therapy. Based on these data, Spectrum Pharmaceuticals is planning for phase II trials and also is seeking a licensing partner outside of the U.S., specifically in Japan and other Asian countries.
November 21, 2011
AMAG Pharmaceuticals issued results from a phase II trial of ferumoxytol for the treatment of iron deficiency anemia and chronic kidney disease. This randomized, active controlled trial, FIRST, enrolled 162 subjects who received an intravenous infusion of ferumoxytol for a total cumulative dose of 1.02 g or an intravenous infusion of iron sucrose for a total cumulative dose of 1.0 g. The subjects treated with ferumoxytol had a comparable increase in hemoglobin (Hgb) at Week 5 from baseline compared with subjects treated with iron sucrose, however, higher Hgb values were observed at all time points following treatment through Week 5 in the ferumoxytol-treated arm compared to the iron sucrose arm. Of the subjects treated with ferumoxytol, 50% achieved a ≥1 g/dL increase in Hgb compared with 42% of subjects treated with iron sucrose. In addition, subjects treated with ferumoxytol had a faster time to response, 28.5 days versus 32.9 days. Ferumoxytol treatment resulted in lower overall rates of adverse events and related adverse events.
FibroGen released interim results from a phase IIb trial of FG-4592 for the treatment of anemia resulting from chronic kidney disease. This randomized, open-label, comparator-controlled study, FG-4592-041, is evaluating several treatment options of FG-4592 for a 16 or a 24 week period. Data are from the first four treatment arms and include 96 subjects with chronic kidney disease who are not on dialysis. Treatment with FG-4592 was designed to increase hemoglobin (Hb) by at least 1 g/dL and maintain Hb concentration in the target range of 11-13 g/dL for the first two arms (arms A and B) treated for 16 weeks, and 10.5-12.0 g/dL in the second two arms (arms C and D) treated for 24 weeks. Results showed that during the treatment period, 96% of all subjects had an increase in Hb of at least 1 g/dL, and 93% had an Hb response. The response rate was 83% in Arm A, which used three times weekly dosing throughout the study, with dose-adjustment decisions made monthly. In Arm B the response rate was 100%; this arm used weight-adjusted initial doses of FG-4592 administered three times weekly during the Hb correction phase, followed by twice weekly dosing during the Hb maintenance phase. The response rate was 91% in Arm C, which used a fixed starting dose of 50 mg thrice weekly. In arm D the response rate was 96%; this arm used a fixed starting dose of 100 mg for four weeks after which dose adjustments were made every four weeks.
December 6, 2010
Keryx issued positive results from a phase III trial of Zerenex for the treatment of hyperphosphatemia in patients with end-stage renal disease on dialysis. This multicenter, randomized, open-label trial enrolled 150 subjects on hemodialysis. Following a two-week washout period, the subjects were randomized to fixed doses of Zerenex 1, 6 or 8 grams per day, for a treatment period of 28 days. The primary endpoint was to demonstrate a dose response in the change of serum phosphorous from baseline (end of washout period) to end of the treatment period (day 28). The study met the primary endpoint, with the regression analysis indicating a highly statistically significant dose response (p<0.0001). In addition, a statistically significant dose response increase in serum bicarbonate was observed and there was no clinically meaningful change in serum calcium. Zerenex appeared to be safe and well-tolerated.
March 15, 2010
AM-Pharma issued positive results from a phase II trial of Alkaline Phosphatase for acute kidney injury. This double blind, placebo controlled, study enrolled 36 subjects with acute kidney injury secondary to sepsis. The subjects received Alkaline Phosphatase intravenously for 48 hours and were followed for 28 days. A composite analysis of all primary renal function efficacy parameters, creatinine clearance, serum creatinine and dialysis requirement showed statistically significant improvement compared to placebo (p≡0.005). Renal creatinine clearance improved more than twice as fast in the treated group during the first 7 days, (p<0.02) resulting in normalization of creatinine clearance for the rest of the 28 days, compared to the placebo group, where creatinine clearance remained impaired (p<0.02). There was a reduction of dialysis requirement after treatment with Alkaline Phosphatase compared to placebo (means: 10 hours versus 53 hours, p≡0.08). Secondary endpoints were also reached with significance. Treatment with Alkaline Phosphatase resulted in shorter stay in the intensive care unit (11 days versus 25 days; p<0.02) and in reduced need for mechanical ventilation (3.9 days versus 6.0 days; p<0.03).
February 4, 2008
AMAG issued positive results from three phase III trials of ferumoxytol as an intravenous treatment of iron deficiency anemia in patients with chronic kidney disease (CKD). These results addressed mortality rates and adverse events and were consistent with previously reported phase III results. The open-label, multi-center, randomized trials enrolled a total of two thousand and seventy four non-dialysis and dialysis-dependent subjects with CKD. The subjects received either intravenous ferumoxytol or oral iron. Overall, thirty-one deaths occurred, none of which were considered to be related to study treatment. The incidence of death was lower in the intravenous ferumoxytol arm (1.1%) compared to the oral iron arm (2.8%). For deaths that occurred within thirty days of the last study treatment, the incidence was also lower with intravenous ferumoxytol, at 0.7%, compared to 1.4% among oral iron subjects. The overall incidences of adverse events (AE) and serious adverse events (SAE) occurring after study treatment were lower following ferumoxytol treatment than following oral iron treatment. The AE rate was 44.0% among ferumoxytol subjects compared to 53.9% among oral iron subjects, and the SAE rate was 9.8% among ferumoxytol subjects compared to 12.1% among oral iron subjects. A NDA for intravenous ferumoxytol is currently under review by the FDA.
July 30, 2007
Advanced Magnetics issued positive results from a phase III trial of ferumoxytol (iv) iron replacement for the treatment of chronic kidney disease (CKD). This open-label, randomized trial enrolled 230 hemodialysis dependent CKD subjects who were receiving stable doses of erythropoietin. Subjects were administered either two 510 mg doses of IV ferumoxytol within one week or 200 mg of oral iron daily for three weeks. The primary endpoint was the mean change in hemoglobin from baseline at day 35 after the first dose. This was reached with statistical significance (ferumoxytol 1.02 +/- 1.13 g/dL versus oral iron 0.46 +/- 1.06 g/dL, p=0.0002). Secondary endpoints included the proportion of subjects with at least a 1.0 g/dL rise in hemoglobin at day 35, and the mean change in serum ferritin from baseline to day 21. These were met as well. In the ferumoxytol arm, 49.1% of the subjects showed at least a 1.0 g/dL rise in hemoglobin at day 35 versus 25% of the oral iron arm (p=0.0002). The mean increase in serum ferritin from baseline to day 21 for the ferumoxytol arm was 356.7 +/- 247.1 ng/mL versus -37.6 +/- 107.0 ng/mL for the oral iron arm (p less than 0.0001). Based on positive phase III results, Advanced Magnetics plans to file a NDA with the FDA in Q4 of 2007.
July 16, 2007
LAB International announced positive interim results from a phase II trial of GHRH for the treatment of chronic kidney disease. This placebo controlled, double-blind trial enrolled malnourished subjects with advanced pre-dialysis chronic renal failure who received placebo or GHRH (1mg/dose) applied subcutaneously twice daily for 28 days. The primary endpoint was to demonstrate an increase in growth hormone (GH) secretion and circulating insulin-like growth factor (IGF-1) levels. This endpoint was achieved. The time-integrated 24-hour endogenous GH concentration after 4 weeks of in the GHRH group was increased 5-fold compared to baseline; no significant change in GH secretion was observed in the placebo group (p = 0.0024). IGF-1 levels remained elevated throughout the entire treatment period, with the median reaching 684 ng/ml for the GHRH arm versus. 398 ng/ml for placebo (p=0.0001) on day 28. When compared to baseline, there was a 2-fold increase in total plasma IGF-1 concentration in the GHRH arm and no substantial increase (1.1) in the placebo group on day 28. Final results are expected in Q3 of 2007.
April 30, 2007
Roche positive results from two phase III trials, (MAXIMA and PROTOS) of Mircera, for the treatment of renal anemia in elderly patients with chronic kidney disease. These trials enrolled a total of 1,245 dialysis subjects with a mean age of 60 years. Subjects were randomized to remain on their current epoetin treatment administered up to three times or week or to be switched directly to Mircera administered intravenously (IV) or subcutaneously (SC) once every two weeks or once every four weeks. Results revealed that Mircera IV and SC maintained stable hemoglobin (Hb) levels in the group switched from epoetin alpha and beta, deviating less than 0.5 g/dL from the start of the trial. Minimal changes from baseline to evaluation in mean Hb levels were seen in subjects less than or equal to 65 and over 65 years (-0.18 vs -0.34 g/dL). A BLA and MAA for Mircera are currently under review by the FDA and EMEA, respectively.
November 27, 2006
Advanced Magnetics reported positive results from a phase III trial of ferumoxytol as an intravenous iron replacement therapy in patients with chronic kidney disease. This trial enrolled 304 non-dialysis dependent chronic kidney disease subjects, who were randomized to receive either two 510 mg doses of ferumoxytol within one week or 200 mg of oral iron daily for three weeks. Treatment with ferumoxytol was well tolerated at repeated dosing. Adverse events occurred in 35.5% of the subjects on ferumoxytol versus 52% of those on oral iron. No drug related serious adverse events were reported for either group. The primary endpoint, a change in hemoglobin at day 35, was met. In the intent to treat population, mean hemoglobin at day 35 in the ferumoxytol group was 0.81 +/- 1.24 g/dl versus the oral iron group at 0.21 +/- 1.04 g/dl, p=0.0002). In the efficacy evaluable group, subjects in ferumoxytol group reached a significantly greater increase in mean hemoglobin versus the oral iron group (ferumoxytol 0.86 +/- 1.23 g/dl vs. oral iron 0.06 +/- 1.08 g/dl, p<0.0001). In addition, Ferumoxytol was more likely to increase baseline hemoglobin by greater than or equal to 1 g/dl compared to oral iron (ferumoxytol 42.3% vs. oral iron 16.1%, p=0.0004) and there was a significantly greater increase in serum ferritin in the ferumoxytol group compared to the oral iron group at Day 21 (ferumoxytol 551.0 +/-301.7 ng/ml vs. oral iron 8.9 +/- 52.2 ng/ml, p<0.0001). Advanced Magnetics plans to submit a NDA to the FDA for ferumoxytol in the second half of 2007.
July 24, 2006
Trigen reported positive results of a phase II trial of TGN 255 for the prevention of clotting during hemodialysis, at the XLIII ERA-EDTA Congress in Glasgow, Scotland. Trial data indicated that the drug was well tolerated, higher doses were associated with decreases in extracorporeal circuit clotting, and dose dependent changes in coagulation parameters (ACT, aPTT, TT) were noted. This open-label multi-center trial enrolled 28 patients, who received various doses of the drug across up to 3 dialysis sessions.
July 10, 2006
Keryx Biopharam announced positive results of a phase II trial of Zerenex for the treatment of hyperphosphatemia in patients with end-stage renal disease on hemodialysis. The drug produced significant dose response in the reduction of serum phosphorous concentration relative to baseline (p=0.0073). The highest dose regimen produced significantly superior reduction from baseline vs. placebo, the trial’s primary endpoint (- 1.5 mg/dL; p<0.01). A significant dose response was also noted in the reduction in calcium x phosphorous product at day 28 (p=0.0158). The highest dose produced significant efficacy in this value vs. placebo as well (-11.7 mg/dL; p<0.01). No serious adverse events were reported. This randomized, double-blind, placebo-controlled, dose-ranging study enrolled 116 subjects, who received one of three doses of the drug (2g, 4g or 6g) or placebo for 28 days.
November 21, 2005
CuraGen reported positive results of a phase I trial of CR002, their monoclonal antibody for the treatment of kidney inflammation. Trial data indicated a positive safety profile, with no serious adverse events reported and good overall tolerability. Pharmacokinetic data indicated that meat elimination half-life was 20.1 to 34.2 days, and pharmacodynamic results indicated binding to the antibody's target molecule (platelet derived growth factor-D) for durations exceeding 20 days. This open- label placebo-controlled study enrolled 40 healthy volunteers, who received one of five single doses of the drug (0.3 mg/kg to 30 mg/kg) or placebo, with subsequent 3 month observational follow-up.
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.
Speedel reported positive results of a phase IIb trial of SPP301 for the treatment of diabetic nephropathy. Study data indicated that the drug significantly reduced urinary albumin excretion rate at all trial doses compared to placebo (p<0.001), with the greatest reductions noted in the two highest trial doses. Total cholesterol scores were also significantly reduced at all doses (p<0.001). Rates of proteinuria were reduced by 30% on top of standard therapy. This randomized, placebo- controlled, double-blind, parallel design study enrolled 286 patients, who received one of 4 doses of SPP301 (5 mg, 10 mg, 25 mg or 50 mg) or placebo once daily for 12 weeks, in addition to standard therapy.
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.<
April 14, 2003
Genelabs Technologies and Johns Hopkins University School of Medicine reported positive results from a late phase trial investigating Prestara (prasterone), a synthetic androgenic hormone for the treatment of systemic lupus erythematosus (SLE or lupus). Results showed that Prestara improved or stabilized overall disease activity and symptoms without deterioration in women with active lupus. Subjects with a SLE Disease Activity Index (SLEDAI) score greater than two showed a 59% rate of response with Prestara compared with 45% on placebo. In addition, subject with a SLEDAI score greater than four showed a 60% rate of response with Prestara compared to 42% for placebo. SLEDAI is an index that measures disease activity by weighting the importance of each organ system involved.
La Jolla Pharmaceuticals reported positive results from phase II and phase III trials investigating Riquent, a B-cell antibody inhibitor for the treatment of lupus renal disease. Phase III trial results demonstrated that Riquent lowered levels of antibodies to double-stranded DNA; however, the trial did not reach statistical significance for its primary endpoint, time to renal flare. Data showed that 55% of Riquent-treated subjects (80/145) had sustained antibody reductions compared to 27% with placebo (41/153). The study enrolled 298 subjects who were treated for up to 22 months. Phase II trial results showed that 59% of Riquent-treated subjects (54/92) had sustained antibody reductions compared to 13% with placebo (13/97). The placebo-controlled study enrolled 189 subjects who were treated for up to 18 months.
March 4, 2003
AVI BioPharma reported positive results from a phase Ib trial investigating Neugene (AVI-4126), an antisense drug for the treatment of kidney disease. Results showed the drug was safe and that kidney impairment did not impact drug levels in the blood. Data indicated that less-frequent dosing of the drug could be effective. The blood half-life of Neugene was approximately 8 to 9 hours, although substantial levels were measured up to 72 hours after dosing. There were no dose-limiting toxicities observed and no subjects were discontinued from the study due to adverse events. The single-center study enrolled 17 subjects with autosomal dominant polycystic kidney disease. Subjects were administered 10, 30, or 90mg of Neugene by intravenous bolus.
June 17, 2002
Phase III trial results indicate that Fosrenol (lanthanum carbonate), a phosphate binder for use in dialysis subjects, did not adversely affect bone over 12 months of continuous therapy. Data also showed that there was no evolution towards low bone turnover states in lanthanum-treated subjects. The multicenter trial included 98 subjects beginning renal dialysis for the first time. Subjects were randomized to receive either lanthanum carbonate or calcium carbonate, which was titrated to a well-tolerated dose that gave acceptable control of serum phosphate. Bone biopsies were taken at the beginning and end of the 12-month study, and blood samples were taken at each visit. Fosrenol is being developed by Shire Pharmaceuticals and AnorMED.
March 18, 2002
Interim phase II trial results indicate that treatment with SangStat's Thymoglobulin results in fewer acute kidney rejections compared to treatment with Novartis' Simulect (basiliximab). Data showed that the incidence of acute kidney rejection was 2.5 times greater for Simulect-treated subjects compared to those who received Thymoglobulin. The randomized comparative trial examined Thymoglobulin versus Simulect as induction therapy in high-risk kidney transplants. There was no statistically significant difference in the rate of severe adverse events between the study arms. An independent Data Safety Monitoring Board has decided to close the study early based on the interim analysis.