May 29, 2017
Otsuka Pharmaceutical issued positive top-line results from an additional phase III clinical trial of tolvaptan in adult patients with autosomal dominant polycystic kidney disease (ADPKD). The multicenter, international, randomized-withdrawal, placebo-controlled, double-blind trial compared the efficacy and safety of tolvaptan (45 to 120mg/day) to placebo. Trial enrollees were adults 18 to 65 years of age with ADPKD-induced chronic kidney disease between late stage two to early stage four (eGFR ranging from 65 to 25 mL/min) and not previously treated with tolvaptan. A total of 1,370 patients were randomized to either tolvaptan or placebo and were treated for a period of 12 months. As in the prior study, tolvaptan resulted in more patients than placebo with increased (>3x upper limit of normal (ULN)) levels of liver enzymes alanine aminotransferase (ALT; 5.6% vs. 1.2%) and aspartate aminotransferase (AST; 3.5% vs. 0.9%); however, none of these patients exhibited total bilirubin greater than 2x ULN. The most common adverse events associated with tolvaptan (incidence >5% and at least 1% more frequent than placebo) included diarrhea (6.9% vs. 3.4%), fatigue (6.8% vs 3.5%) and polyuria (5.3% vs. 1.6%). The trial was completed to supply confirmatory data to the previous study to address the Complete Response Letter (CRL) issued by the FDA in 2013 for an NDA for tolvaptan in the treatment of adults with ADPKD. Tolvaptan is approved for the treatment of adult patients with ADPKD in Japan, the EU and other countries.
January 11, 2016
Ardelyx has issued positive results of an open label clinical study evaluating the pharmacodynamic (PD) activity of RDX022 in healthy adult volunteers. The study consisted of a two-day treatment-free baseline period and a four-day treatment period. The study included four cohorts; in each cohort, 12 subjects received RDX022 and three subjects received a similar dose of sodium polystyrene sulfonate (SPS) for a total of 60 subjects. RDX022 was administered at 4.6g BID (9.2 g/day), 6.9g BID (13.8 g/day), 4.6g TID (13.8g/day) and 9.2g TID (27.5g/day), and resulted in a mean increase of fecal potassium from baseline of 888mg/day, 1,791mg/day, 1,408mg/day, and 1,670mg/day, respectively. RDX022 was generally well-tolerated at all doses and demonstrated comparable results to those observed with sodium polystyrene sulfonate (SPS). Other fecal electrolytes were monitored during the study and no unexpected changes were observed; in particular, fecal magnesium remained unchanged from baseline. The study demonstrated that RDX022, Ardelyx’s proprietary potassium binder for the treatment of hyperkalemia, effectively binds potassium in the gastrointestinal tract supporting plans to proceed with a phase III clinical program currently expected to begin in the second half of 2016. RDX022 was generally well-tolerated at all doses administered (up to 27.5g/day) in the study. Based on discussions with the FDA, the company is pursuing a 505(b)(2) regulatory pathway for RDX022.
November 23, 2015
ZS Pharma has issued interim results of a global, multicenter, phase III trial of ZS-9
(sodium zirconium cyclosilicate) for hyperkalemia. The trial investigated the long-term safety and efficacy of ZS-9 in 750 patients with hyperkalemia (potassium levels >5mEq/L) from sites in the U.S., E.U., Australia and South Africa. Patients with hyperkalemia receive a 10-gram dose of ZS-9 administered three times daily for until achieving normokalemia during the 24- to 72-hour acute phase of the study. Patients that achieve normokalemia then receive a 5-gram dose of ZS-9 administered once-daily with the ability to titrate dose in 5-gram increments or decrements, if needed, to maintain normokalemia. The primary endpoint is safety and tolerability, and the secondary endpoint is the proportion of patients with average serum potassium =5.1 mEq/L between month three and month 12. Ninety-nine percent of patients achieved normokalemia in the acute phase on 10 grams TID of ZS-9. Mean potassium levels were maintained at 4.6mEq/L throughout the 12-month, long-term treatment phase. The primary efficacy endpoint was met with 87% to 92% of patients maintained at an average serum potassium =5.1mEq/L between month three and month 12. Normokalemia was maintained with patients receiving once-daily 5-gram (64%), 10-gram (30%) or 15-gram (5%) doses of ZS-9. There were no deaths in the acute phase; five deaths (0.7%) occurred in the long-term phase, but none were considered to be related to the study drug.
July 27, 2015
Relypsa issued results of a phase II study of
Patiromer for Oral Suspension (Patiromer
FOS) in chronic kidney disease (CKD) and mild
or moderate hyperkalemia. AMETHYST-DN was
a multicenter, randomized, open-label, dose-ranging
trial that included 306 patients with
CKD stages 3 to 5, as well as type 2 diabetes. All
patients were taking RAAS inhibitors to treat
their CKD prior to and during study treatment
and had mild-to-moderate hyperkalemia. Mild
hyperkalemia was defined as potassium levels
>5–5.5 mEq/L and moderate hyperkalemia as
>5.5–<6 mEq/L. Study participants received
one of three randomized total daily starting
doses of Patiromer FOS: 8.4g, 16.8g or 25.2g for
those with mild hyperkalemia, and 16.8g, 25.2g
or 33.6g for those with moderate hyperkalemia.
Through week 52, significant mean decreases in
potassium from baseline at each monthly visit
were observed (p<0.001) and the vast majority
of patients with mild (83.1-92.7%) or moderate
hyperkalemia (77.4-95.1%) had potassium
levels within the target range (3.8-5mEq/L).
Significant reductions in mean potassium were
seen at the first post-baseline assessment, approximately
48 hours after Patiromer FOS initiation,
in both mild and moderate hyperkalemia
patients (p<0.001). After discontinuing treatment
with Patiromer FOS, significant increases
in mean potassium levels were observed by day
3 in both patient groups (mild hyperkalemia:
0.25 [0.19-0.31] mEq/L; moderate hyperkalemia:
0.33 [0.20-0.46] mEq/L; p<0.001). The most
common SAE was worsening of CKD (2%).
June 8, 2015
Amgen reported results of two pivotal phase III, global, randomized, placebo-controlled trials evaluating AMG 416 for secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) receiving hemodialysis. Both studies met the primary endpoint, demonstrating that a greater proportion of patients in the AMG 416 groups achieved a greater than 30% reduction in parathyroid hormone (PTH) during the efficacy assessment phase compared with placebo. The two 26-week, double-blind studies enrolled 1,023 patients who received AMG 416 or placebo three times per week by intravenous injection at the end of each hemodialysis treatment. Doses ranged from a minimum of 2.5mg to a maximum of 15mg. The primary endpoint of both studies was the proportion of patients achieving greater than 30% reduction in PTH during the efficacy assessment phase, defined as weeks 20 through 27. Secondary endpoints included the proportion of patients with PTH less than or equal to 300pg/mL, and percent reductions in PTH, albumin adjusted calcium (cCa), phosphate (P) and cCa x P. In the AMG 416 group, 74.7% of patients achieved a greater than 30% reduction from baseline in PTH compared with 8.9% in the placebo arm. Furthermore, a statistically significant proportion of patients (51.5%) randomized to receive AMG 416 achieved PTH less than or equal to 300pg/mL, compared with 5.9% in the placebo-controlled group, despite similar baseline mean PTH values of 724pg/mL and 716pg/mL, respectively. Significant reductions in phosphate as well as fibroblast growth factor 23 (FGF23) also were observed, with two-thirds of AMG 416-treated patients experiencing a greater than 30% reduction in FGF23 concentrations compared with 30% of placebo-treated patients. Reductions in serum calcium were observed and symptomatic hypocalcemia occurred more frequently in patients treated with AMG 416 compared to placebo (7% v. 0.2%, respectively). Additional adverse events included muscle spasms and gastrointestinal symptoms (e.g. nausea and vomiting), and they were reported more frequently with AMG 416 compared with placebo. Rates of death, adjudicated major non-fatal cardiovascular events and seizures were similar in both groups.
May 25, 2015
Phosphate Therapeutics released results of a phase IIb study of PT20 for hyperphosphataemia
related to dialysis dependent chronic kidney disease (DD-CKD). The multicenter, placebo-
controlled, randomized study enrolled 150 subjects and clearly met its primary endpoint (p<0.0001) demonstrating that PT20 successfully
lowered serum phosphate levels compared to placebo, while all secondary analyses of the primary endpoint were also statistically significant (p<0.01). All of the study’s PT20 dose groups showed a phosphate reduction at day 28 compared to baseline and this reduction was dose-related. PT20 was very well-tolerated with less than 5% of the patients who received study medication withdrawing because of adverse events; and no serious adverse events were considered related to study medication.
March 9, 2015
Amgen issued results of a head-to-head
phase III study comparing AMG 416 with
cinacalcet for the treatment of secondary
hyperparathyroidism (SHPT) in patients
with chronic kidney disease (CKD) receiving
hemodialysis. The randomized, active-controlled,
study ran over 26 weeks and enrolled 683
patients. Patients randomized to treatment
with AMG 416 received intravenous (IV)
doses of AMG 416 three times per week at
the end of each dialysis session and daily oral
doses of placebo tablets. Subjects randomized
to treatment with cinacalcet received
daily oral doses of cinacalcet tablets and IV
doses of placebo three times per week at the
end of each dialysis session. The study met
the primary endpoint of non-inferiority of
AMG 416 compared to cinacalcet, measured
as the achievement of a greater than 30%
reduction from baseline in mean pre-dialysis
serum intact parathyroid hormone (PTH)
levels during the Efficacy Assessment Phase
(EAP), defined as the period between weeks
20 and 27. Further, AMG 416 was statistically
significantly superior to cinacalcet in the
secondary endpoints of the proportion of
patients, achieving greater than 50% (52.4%
v. 40.2%) and greater than 30% (68.2% v.
57.7%) PTH reduction from baseline during
the EAP. Treatment-emergent adverse
events (TEAEs) were reported in 92.9% and
90% of patients who received AMG 416 and
cinacalcet, respectively. Treatment-emergent
events related to cardiac failure were reported
in 3% of patients who received AMG
416 v. 0.6% in the cinacalcet group. Serious
adverse events were reported in 25.1% and
27.3% of patients who received AMG 416 and
cinacalcet, respectively. Fatal adverse events
were reported in 2.7% for the AMG 416 arm
and 1.8% for the cinacalcet arm.
December 1, 2014
ZS Pharma released results of a phase
III study of ZS-9 (sodium zirconium
cyclosilicate) for the treatment of hyperkalemia.
The a global, prospective, randomized,
double-blind, placebo-controlled trial met the
primary efficacy endpoint by demonstrating
all three doses (5g, 10g and 15g) of once daily
ZS-9 maintained mean potassium at lower
levels than placebo over the 28-day treatment
period (p-value <=0.0001 all doses) with
significantly higher proportions of patients
having mean serum potassium (K+) levels in
the normal range while on ZS-9 than placebo
(80%, 90% and 94% at the 5g, 10g and 15g
dose, respectively, compared with 46% on
placebo). In the open-label acute phase, serum
potassium levels declined from 5.6mEq/L at
baseline to 4.5mEq/L with 98% of patients
achieving normokalemia within 48 hours of
beginning treatment. Time to onset of activity
with ZS-9 was rapid with the median time to
normokalemia of 2.2 hours. Responses were
larger in patients with severe hyperkalemia
(K+ >=6.0 mEq/L), with mean changes of
-0.5mEq/L at one hour, -0.7mEq/L at two hours
and -1.5mEq/L at 48 hours. The adverse events
with the highest rates were anemia, constipation,
edema, hypokalemia, nasopharyngitis
and upper respiratory tract infections.
August 25, 2014
Amgen issued results of a second phase III
trial of AMG 416 for the treatment of secondary
hyperparathyroidism (SHPT) in patients
with chronic kidney disease (CKD). The
26-week, randomized, double-blind, placebo-controlled
trial gave subjects AMG 416 or
placebo three times per week by intravenous
injection with each hemodialysis treatment.
Doses ranged from a minimum of 2.5mg to
a maximum of 15mg. In the AMG 416 group,
74% of patients achieved a >30% reduction
from baseline in PTH compared with 8.3%
in the placebo arm, a statistically significant
result. Secondary endpoints included the
percent change from baseline during the EAP
in serum phosphorus (P) concentration (mean
changes of -7.71% and -1.31% among patients
in the AMG 416 and placebo arms, respectively)
and corrected calcium (cCa) concentration
(mean changes of -7.29% and 1.18%
among patients in the AMG 416 and placebo
arms, respectively). Both of these secondary
endpoint results were statistically significant.
Treatment-emergent adverse events (TEAEs)
were reported in 91.6% and 78.7% of patients
who received AMG 416 and placebo, respectively.
TEAEs that were reported in >10% of patients
who received AMG 416 included (AMG
416 v. placebo, respectively): blood calcium
decreased (61% and 8.3%), nausea (12.4% and
5.1%), muscle spasms (12% and 7.1%) and
vomiting (10.4% and 7.1%).
August 11, 2014
Quark Pharmaceuticals released results of a phase II trial of QPI-1002 for the prophylaxis of delayed graft function (DGF) in deceased donor kidney transplant patients. The multi-center, placebo-controlled, randomized, prospective and double-blinded study evaluated the clinical activity of QPI-1002 (administered as 10mg/kg single bolus IV dose at 30 minutes after circulatory reperfusion is achieved to the transplanted organ) in end-stage kidney disease dialysis-dependent patients undergoing
deceased donor kidney transplantation. QPI-1002 treatment significantly increased the dialysis-free survival (time to first dialysis) in the first post-transplant month (Log rank p=0.04), reduced the mean duration of the first course of dialysis (13.4 v. 25.3 days) and reduced the number of dialysis sessions required in the first 30 days post-transplant (6.0 v. 11.2). By the end of the six-month study observation period, the total number of dialysis sessions in all efficacy evaluable patients treated with QPI-1002 was 1.5-fold lower compared to placebo group (375 v.. 561 p=0.059).
May 5, 2014
Concert Pharmaceuticals issued
results of a phase II trial of CTP-499 in
patients with diabetic kidney disease.
The placebo-controlled, multi-center
trial involved three parts: a double-blind,
randomized, parallel, two-arm, placebocontrolled
study evaluating urinary albumin
to creatinine ratio (UACR) of 600mg
CTP-499 twice daily for 24 weeks (151 of
182 patients enrolled completed part 1);
an optional blinded extension study in
which all patients who completed part 1
were eligible to continue receiving 600mg
of CTP-499 or placebo twice daily for an
additional 24 weeks (123 of 143 patients
enrolled completed part 2); up to 48
weeks of open-label treatment and receive
600mg of CTP-499 twice daily, currently
ongoing. The mean serum creatinine
level in the 65 patients receiving CTP-499
increased by 0.13mg/dL compared to an
increase of 0.21mg/dL in the 58 patients
receiving placebo through the 48 weeks
of treatment (p = 0.057), reflecting a 38%
improvement. At 48 weeks, UACR in patients
receiving CTP-499 increased 24mg/g from
baseline compared to 223mg/g increase
in patients receiving placebo (p = 0.097).
Treatment with CTP-499 resulted in 52%
less urinary fibronectin (p = 0.0081) and
18% less plasma collagen IV (p = 0.022)
after 48 weeks compared to placebo. An
end-of-phase II meeting request has been
submitted to the FDA, and the company
intends to discuss a possible phase III.
March 24, 2014
La Jolla Pharmaceutical released results of
a phase II trial of GCS-100 for the treatment of
chronic kidney disease (CKD). The phase II study
was a blinded, multi-center, randomized clinical
trial that enrolled 121 patients with stage 3b
or 4 CKD. Patients were randomly assigned
1:1:1 to treatment with placebo, 1.5mg/m2 of
GCS-100, or 30mg/m2 of GCS-100. Patients
received the assigned treatment weekly for
eight weeks followed by a four-week follow-up
period. Specifically, a dose of 1.5mg/m2 led
to a statistically significant (p=0.045) increase
in estimated glomerular filtration rate (eGFR)
compared to placebo between baseline and
end of treatment. At the 30mg/m2 dose, there
was no statistically significant difference. Potassium,
uric acid and blood urea nitrogen (BUN)
all improved at the 1.5mg/m2 dose level. There
were no serious adverse events (SAEs) in the
1.5mg/m2 dose group compared to two in the
placebo group and two in the 30mg/m2 group.
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.