May 1, 2017
Gilead Sciences released results of two ongoing phase III studies evaluating the safety and efficacy of daily Vemlidy (tenofovir alafenamide, TAF 25mg) in immune active patients and in patients switching from Gilead’s Viread (tenofovir disoproxil fumarate, TDF 300mg) for HBeAg-negative and HBeAg-positive chronic hepatitis B virus (HBV) infection with compensated liver disease. The two randomized, double-blinded studies (Studies 108 and 110) demonstrate continued advantages of treatment with Vemlidy over Viread between week 48 and week 96. Virologic response rates at week 96 were 90% (n=257/285) and 91% (n=127/140) in HBeAg-negative patients (Study 108) receiving Vemlidy and Viread, respectively. In HBeAg-positive patients (Study 110), virologic response rates at week 96 were 73% (n=423/581) and 75% (n=218/292) in the Vemlidy and Viread groups, respectively. In both studies, a greater percentage of patients taking Vemlidy achieved normalization of ALT levels relative to patients taking Viread as measured by both central laboratory criteria, and by the American Association for the Study of Liver Diseases (AASLD) criteria. Patients receiving Vemlidy also demonstrated ongoing benefits at week 96 in bone and renal safety parameters, including smaller declines from baseline in hip and spine bone mineral density (BMD) and smaller declines from baseline in estimated creatinine clearance compared with patients taking Viread in both studies. Similar rates of adverse events and low and similar rates of adverse events leading to discontinuation were observed in both treatment arms. Viral resistance analyses showed no resistance to Vemlidy or Viread at week 96.
August 15, 2016
Merck (MSD) reported results of a phase III trial of ZEPATIER (elbasvir and grazoprevir) 50mg/100mg tablets in patients with chronic hepatitis C (HCV) genotype (GT) 1, GT4 and GT6 infection receiving opioid agonist therapy (OAT) (methadone and buprenorphine), commonly used to treat opioid addiction. Efficacy results from the randomized, double-blind, placebo-controlled C-EDGE CO-STAR trial showed 92% (184/201) of patients receiving ZEPATIER for 12 weeks in the study’s immediate treatment group achieved SVR12, with comparable rates across GT1a (94%, 144/154), GT1b (93%, 28/30) and GT4 (92%, 11/12) patients; in the limited number of GT6 patients, SVR12 was 20% (1/5). A supportive analysis showed that the vast majority of patients were adherent to therapy, despite the ongoing use of drugs of potential abuse (e.g., cocaine, heroin, amphetamines) by the majority of patients throughout the trial. The rates of adverse events were generally comparable between active treatment and placebo groups, with the most common adverse events (greater than 10%) in both groups including fatigue (16%, 20%), headache (12%, 13%) and nausea (11%, 9%), respectively.
May 16, 2016
Dynavax Technologies released results of a phase III trial comparing hepatitis B vaccine HEPLISAV-B with the vaccine Engerix-B in adults 18 to 70 years of age. HBV-23 was a randomized, observer-blinded, active-controlled, multicenter study. Participants were randomized to HEPLISAV-B or Engerix-B in a two to one ratio. They were stratified into two age groups, 18 to 39 years and 40 to 70 years. Two doses of HEPLISAV-B were given one month apart compared to the conventional Engerix-B regimen of three doses given over six months. HEPLISAV-B participants were followed for 52 weeks after the last dose, and Engerix-B participants were followed for 28 weeks after the last dose. HEPLISAV-B demonstrated statistically significant higher protection rates than Engerix-B in both age groups. The seroprotection rate in all participants who received HEPLISAV-B was 95% compared to 81% for Engerix-B. Of participants 18 to 39 years of age, 99% who received HEPLISAV-B and 93% who received Engerix-B were seroprotected. In participants 40 to 70 years of age, a larger difference in seroprotection rates was seen with the HEPLISAV-B rate of 95% compared to 79% for Engerix-B. The FDA has established September 15 as the Prescription Drug User Fee Act action date for the HEPLISAV-B Biologics License Application.
May 2, 2016
Merck & Co. reported results of a phase III trial of Zepatier (elbasvir and grazoprevir) 50mg/100mg tablets in chronic hepatitis C (HCV) patients with inherited blood disorders (C-EDGE IBLD). C-EDGE IBLD is a randomized, double-blind, placebo-controlled study. Patients were randomized in a 2:1 ratio to either an immediate treatment group (ITG; 12 weeks of Zepatier) or deferred treatment group (DTG; 12 weeks of placebo as control arm, followed by 12 weeks of open-label Zepatier). The primary efficacy endpoint for the study was the proportion of patients in the ITG who achieved SVR12. Safety and tolerability were evaluated by comparing subjects receiving Zepatier in the ITG (n=107) to those receiving placebo in the DTG (n=52). Following 12 weeks of treatment with Zepatier, 93% of patients in the ITG (100/107) achieved SVR12 (virologic cure). Six patients relapsed following 12 weeks of treatment; five of these patients (3 GT1a, 1 GT1b and 1 GT4) had detectable NS5A resistance-associated polymorphisms at baseline. The study did not evaluate other Zepatier-based dosage regimens or durations. Zepatier was approved by the FDA in January 2016, based in part on prior studies from the phase III program.
March 7, 2016
Bristol-Myers Squibb issued results of a phase III trial of daclatasvir in combination with asunaprevir for 24 weeks in Asian (non-Japanese) patients with genotype 1b chronic hepatitis C (HCV). The open-label study evaluated daclatasvir and asunaprevir in interferon- ineligible and/or intolerant non-Japanese Asian patients with chronic HCV genotype 1b infection. Patients received daclatasvir 60mg (tablet) once daily plus asunaprevir 100mg (soft capsule) twice daily for 24 weeks. The primary endpoint was sustained virologic response at post-treatment week 24 (SVR24). The study treated 159 patients overall, 80% from mainland China, 11% from Korea and 9% from Taiwan, including patients with cirrhosis (33%), IL28B nonCC genotypes (40%) and aged =70 years (4%). In the study, 91% of patients from China achieved SVR24, which rose to 98% of patients without NS5A resistance-associated variants (RAVs) at baseline. SVR24 results were similarly high across all subgroups with genotype 1b HCV, including those with cirrhosis (90%), and patients from Korea (94%) and Taiwan (87%). SVR24 rates were also higher in all patients without baseline NS5A RAVs (n=137/139 [99%]), regardless of the presence (98%) or absence (99%) of cirrhosis, and lower in patients with baseline NS5A RAVs (n=8/19 [42%]). Baseline NS5A RAVs were present in 12% of patients. HCV NS5A RAVs exist naturally (albeit in lower prevalence v. wildtype) and can emerge after virologic response failure. In the trial presented today, across all patient cohorts, all serious adverse events (SAEs) (n=5/159 [3%]), grade 4 laboratory abnormalities (n=3/159 [1.9%]) and deaths (n=1/159 [1%]) that occurred on treatment were unrelated to the study drugs. Two patients discontinued due to adverse events (AEs). The most common AEs (>5% of patients) were decrease in platelets (9%), upper respiratory tract infection (8%), ALT increase (7%), ANC decrease (7%), monocyte decrease (6%), white blood cell decrease (6%), thrombocytopenia (6%) and pruritus (6%).
January 11, 2016
Gilead Sciences has reported results of two phase III studies (Studies 108 and 110) of tenofovir alafenamide (TAF) 25mg in treatment-naïve and treatment-experienced adults with HBeAg-negative and HBeAg-positive chronic hepatitis B virus (HBV) infection. Studies 108 and 110 are randomized, double-blind, 96-week clinical trials among 1,298 treatment-naïve and treatment-experienced patients with chronic HBV. In Study 108, 425 HBeAg-negative patients were randomized 2:1 to receive TAF (n=285) or Viread (n=140). In Study 110, 873 HBeAg-positive patients were randomized 2:1 to receive TAF (n=581) or Viread (n=292). In Study 108, evaluating HBeAg-negative patients, 94% (n=268/285) of patients receiving TAF and 92.9% (n=130/140; CI -3.6% to +7.2%, p=0.47) of patients receiving Viread achieved HBV DNA below 29 IU/mL at week 48. In Study 110, evaluating HBeAg-positive patients, 63.9% (n=371/581) of TAF patients and 66.8% (n=195/292; CI -9.8% to +2.6%, p=0.25) of Viread patients achieved HBV DNA below 29 IU/mL at week 48. Discontinuations due to adverse events were uncommon in both treatment arms (0.7% (n=2) for TAF v. 0.7% (n=1) for Viread in Study 108, and 1% (n=6) for TAF v. 1% (n=3) for Viread in Study 110). The most commonly reported adverse events in both studies included headache, upper respiratory tract infection, nasopharyngitis and cough, and occurred at similar rates in patients receiving either TAF or Viread. Gilead plans to submit regulatory applications for TAF for chronic HBV in the U.S. and the E.U. in the first quarter of 2016.
November 30, 2015
Merck has issued results of a phase III trial
of elbasvir/grazoprevir (50mg/100mg)
in patients with chronic hepatitis C virus
(HCV) genotypes (GT) 1, 4 or 6 infection who
inject drugs and are receiving opioid agonist
therapy (OAT). The randomized, double-blind,
placebo-controlled study enrolled 301 patients
to one of two study arms: an immediate
treatment group (ITG) that received elbasvir/
grazoprevir (blinded) for 12 weeks (n=201),
and a deferred treatment group (DTG) that
received 12 weeks of placebo (control arm)
followed by a four-week follow-up period and
then elbasvir/grazoprevir (open-label) for 12
weeks (n=100). In the modified full analysis
set (mFAS), 96% of GT1a patients (147/153),
97% of GT1b patients (28/29), 100% of GT4
patients (11/11) and 60% of GT6 patients (3/5)
achieved virologic cure when treated with
elbasvir/grazoprevir for 12 weeks. Results for
patients with GT6 infection were limited by
the small number of GT6 patients enrolled. In
a supportive efficacy analysis based on the full
analysis set, which included all subjects with
HCV GT1, 4 or 6 infection who received at least
one dose of study drug, the overall SVR12 rate
in the ITG was 92% (184/201).
October 5, 2015
Gilead Sciences has issued results of
phase III studies (ASTRAL-1, ASTRAL-2, ASTRAL-
3 and ASTRAL-4) of sofosbuvir (SOF)
with velpatasvir (VEL) for the treatment
of genotype 1-6 chronic hepatitis C virus
(HCV) infection. In the ASTRAL-1, ASTRAL-2,
and ASTRAL-3 studies, 1,035 patients with
genotype 1-6 HCV infection received 12
weeks of SOF/VEL. Among those patients,
21% had compensated cirrhosis and 28%
had failed prior treatments. The ASTRAL-4
study randomized 267 patients with decompensated
cirrhosis (Child-Pugh class B) to
receive 12 weeks of SOF/VEL with or without
ribavirin (RBV), or 24 weeks of SOF/VEL. The
primary endpoint for all studies was SVR12.
Of the 1,035 patients treated with SOF/VEL
for 12 weeks in the ASTRAL-1, ASTRAL-2 and
ASTRAL-3 studies, 1,015 (98%) achieved the
primary efficacy endpoint of SVR12. Of the
20 patients who did not achieve SVR12, 13
patients (1.3%) experienced virologic failure
and seven did not complete an SVR12 visit
(e.g., lost to follow-up). Twelve of the 13
virologic failure patients relapsed (two genotype
1 HCV-infected patients and 10 genotype
3 HCV-infected patients). There was
one patient with documented re-infection.
No patients with genotype 2, 4, 5 or 6 HCV
infection had virologic failure. In ASTRAL-4,
patients with Child-Pugh class B cirrhosis
receiving SOF/VEL+RBV achieved higher
SVR12 rates than patients receiving SOF/VEL
for 12 or 24 weeks. Among genotype 1 and
3 patients treated with SOF/VEL+RBV for 12
weeks, the SVR12 rates were 96% and 85%,
respectively. The FDA has assigned the SOF/
VEL fixed-dose combination a Breakthrough
March 2, 2015
AbbVie issued results of the phase II portion
of its phase II/III open-label study of VIEKIRA
PAK and ribavirin (RBV) in genotype 1 chronic
hepatitis C patients with human immunodeficiency
virus type 1 (HIV-1) co-infection. The
study is an ongoing, multi-center, randomized,
open-label study evaluating the efficacy and
safety of VIEKIRA PAK (ombitasvir, paritaprevir,
ritonavir (25/150/100mg once daily) and
dasabuvir (250mg twice daily) with RBV (weight
based dosing of 1000mg or 1200mg per day
divided twice daily) for 12 or 24 weeks in adult
patients with chronic GT1 HCV infection with
or without compensated liver cirrhosis who
also are infected with HIV-1. The study showed
patients co-infected with genotype 1 (GT1)
hepatitis C virus (HCV) and HIV-1 receiving
VIEKIRA PAK and ribavirin (RBV) for 12 weeks or
24 weeks achieved sustained virologic response
rates 12 weeks post-treatment (SVR12) of 94%
(n=29/31) and 91% (n=29/32), respectively. The
SVR12 rates were 91% (n=51/56) for subjects
with HCV GT1a infection and 100% (n=7/7) for
those with HCV GT1b infection. The most common
adverse events occurring in at least 10%
of patients in TURQUOISE-I were fatigue (48%),
insomnia (19%), nausea (17%), headache (16%),
itching (13%), cough (11%), irritability (10%)
and yellowing of the eyes (10%).
February 16, 2015
AbbVie issued results of a phase III study
of ombitasvir/paritaprevir/ritonavir (OBV/
PTV/r) in patients with genotype 1b (GT1b)
chronic hepatitis C virus (HCV) infection in
Japan. The multi-center study was designed to
evaluate the efficacy and safety of 12 weeks of
treatment with OBV/PTV/r in adult Japanese
patients (n=363) with chronic genotype 1b
hepatitis C virus infection. Patients included
those without cirrhosis and with compensated
cirrhosis who were new to therapy (treatment-naive)
or had failed previous treatment with
interferon with or without ribavirin (treatment-experienced).
The study consists of two
sub-studies. Sub-study one included patients
without cirrhosis randomized to OBV/PTV/r or
placebo. Sub-study two included patients with
compensated cirrhosis, who received openlabel
treatment with OBV/PTV/r. The primary
endpoint of the GIFT-I study was achieved,
demonstrating a 95% (n=106/112) sustained
virologic response rate at 12 weeks post treatment
(SVR12) in the sub-group of previously
untreated, non-cirrhotic adult GT1b Japanese
patients who were eligible for therapy with
interferon (IFN) and had a high viral load. In
patients without cirrhosis, the most commonly
reported adverse events in the treatment arm
were nasopharyngitis (16.7% OBV/PTV/r v.
13.2% placebo), headache (8.8% OBV/PTV/r v.
9.4% placebo) and oedema peripheral (5.1%
OBV/PTV/r v. 0% placebo). Two patients without
cirrhosis (0.9%) discontinued treatment due
to adverse events. Within the primary efficacy
patient population, there were no on-treatment
virologic failures and 2.8% of patients (n=3/109)
experienced relapse. A local regulatory submission
is anticipated in the first quarter of 2015.
December 1, 2014
Merck issued results from a phase II
clinical trial evaluating grazoprevir/elbasvir
(MK-5172/MK-8742) with or without ribavirin
(RBV) in treatment-naïve and previously-treated
patients with chronic hepatitis C virus (HCV)
genotype 1 (GT1) infection. The study was a
randomized, dose response, parallel-group,
multiple-site, double-blind clinical trial. A total
of 471 patients with chronic HCV GT1 infection
with HCV RNA levels of =10,000IU/mL were
enrolled and randomized across 16 arms. The
patients include hard-to-cure sub-populations,
including treatment-naïve patients with liver
cirrhosis (12- and 18-week arms, with and without
RBV) and prior-null responder patients with
and without cirrhosis (12- and 18-week arms,
with and without RBV). The rates of sustained
viral response, 12 weeks after the completion
of therapy (SVR12) were ≥90% regardless of
treatment duration or co-administration of
RBV. The rate of virologic failure was 5% (6/123)
in treatment-naïve cirrhotic patients and 3%
(4/130) in the null-responder population.
Treatment-naïve, non-cirrhotic mono-infected
GT1 patients and non-cirrhotic HCV GT1/HIV
co-infected patients treated for 12 weeks
with grazoprevir/elbasvir with or without
RBV, demonstrated high rates of SVR12.
Among this patient population treated for
12 weeks, the overall rate of virologic failure
was 4% (7/188), including three breakthrough
failures and four relapses, in both mono- and
co-infected patients. In patients treated for
eight weeks, the rate of virologic failure was
17% (5/30), with five relapses. The results supported
the advancement of grazoprevir/elbasvir
into a phase III clinical development
for hard-to-cure patients.
November 24, 2014
AbbVie reported results of a phase II study
of ribavirin (RBV) in patients co-infected with
genotype 1 (GT1) hepatitis C virus (HCV) and
HIV-1. The ongoing, multi-center, randomized,
open-label study combined three direct-acting
antivirals (ombitasvir/ABT-450/ritonavir and
dasabuvir) with RBV (weight-based dosing of
1000mg or 1200mg per day divided twice daily).
Subjects achieved sustained virologic response
rates 12 weeks post-treatment (SVR12) of 93.5%
(n=29/31) and 90.6% (n=29/32), respectively.
Results also showed non-cirrhotic liver transplant
patients with recurrent GT1 HCV and new
to treatment after transplantation achieved a
SVR12 rate of 97.1% (n=33/34) and a sustained
virologic response rate 24 weeks post-treatment
(SVR24) of 97.1% (n=33/34). No patients discontinued
treatment due to adverse events in either
the 12-week or 24-week arm.
Bristol-Myers Squibb released results of a
phase III study of DCV-TRIO fixed-dose combination
(daclatasvir 30mg, asunaprevir 200mg
and beclabuvir 75mg) in non-cirrhotic and
cirrhotic genotype 1 hepatitis C patients. The
open-label study evaluated a 12-week regimen
of the DCV-TRIO without ribavirin in treatmentnaïve
and treatment-experienced non-cirrhotic
patients. Non-cirrhotic treatment-naïve patients
(n=312) and treatment-experienced patients
(n=103) received the DCV-TRIO fixed-dose
combination in one pill twice daily for 12 weeks,
with 24 weeks of follow-up. The majority of the
patients (73%) were genotype 1a, and 91% of all
patients achieved sustained virologic response
12 weeks after treatment (SVR12). Ninety-two
percent of treatment-naive patients and 89% of
treatment-experienced patients achieved cure,
without the use of ribavirin.
November 3, 2014
Regulus Therapeutics released results
evaluating RG-101 for the treatment of
hepatitis C virus infection (HCV). Sixteen HCV
patients were enrolled with multiple genotypes,
10GT1s, 5GT3s and 1GT4. Fourteen
patients, eight naïve and six who experienced
viral relapse after a prior IFN-containing regimen,
received a single subcutaneous dose
of 2mg/kg of RG-101 as monotherapy, while
two patients received placebo. In the 14 HCV
treated patients, there was a mean viral load
reduction of 4.1 log(10) at day 29 (range -5.8
log(10) to -2.3 log(10)). Six out of 14 patients
had HCV RNA levels below the limit of quantification
at day 29 and the three patients from
this group who have reached day 57 still have
HCV RNA levels below the limit of quantification.
RG-101 is safe and well-tolerated with
no serious adverse events reported to date.
Regulus plans to file an IND application with
the FDA in the first quarter of 2015 and plans
to initiate a phase II DAA combination study
of RG-101 in HCV patients in the second
quarter of 2015.
October 27, 2014
Hepatera reported results of two phase
IIa studies of Myrcludex B in patients with
chronic hepatitis B (HBV) and delta (HDV).
A phase IIa trial investigating effects of
several Myrcludex B doses in 40 patients
with chronic HBV infection showed the
drug was well-tolerated. A dose-dependent
effect on HBV DNA was observed: >1 log10
HBV DNA decline at week 12 occurred in 6/8
(75%) patients receiving 10mg Myrcludex B,
while this occurred less often in the remaining
dose groups (7/40; 17%). The HBV DNA
response was maintained in 10mg patients
through week 24. In a phase IIa trial in
chronic HDV infection with 24 patients, Myrcludex
B was investigated as monotherapy
v. combination with pegylated interferon
alpha for 24 weeks; a control arm received
pegylated interferon alpha alone. Myrcludex
B was well-tolerated both as monotherapy
and in combination with interferon. Myrcludex
B has shown strong single agent efficacy
against HDV. Six out of seven evaluable
patients experienced >1 log10 HDV RNA decline
at week 24; two patients became HDV
RNA negative and in two others the values
dropped below the limit of quantification. In
the combination arm, all patients had HDV
RNA decline and five were HDV RNA negative
at week 24. Importantly, ALT normalized
in four Myrcludex B monotherapy patients
at week 24.
April 28, 2014
Merck issued results of an ongoing, multiarm,
phase II trial combining MK-5172 and
MK-8742 for the treatment of chronic HCV
Genotype 1 infection (GT1). The two-part,
parallel-group, randomized (within group) trial
evaluated different treatment durations of MK-
5172 (100mg once daily) plus MK-8742 (50mg
once daily), with or without RBV. In an interim
analysis of treatment-naïve, non-cirrhotic
patients administered a 12-week regimen, a
sustained viral response (SVR) was observed in
98% (42/43) of patients administered
MK-5172/MK-8742 alone and 94% (75/80)
in those administered MK-5172/MK-8742
plus RBV. The most common adverse events
recorded in the RBV and RBV-free treatment
groups, respectively, were fatigue (32%, 23%),
headache (20%, 33%), nausea (21%, 16%),
diarrhea (13%, 9%) and insomnia (13%, 7%).
There were no early discontinuations due to
drug-related adverse events and no clinically
significant abnormalities detected in routine
laboratory analysis of hematologic markers.
April 21, 2014
Gilead Sciences reported results of a
phase II studies of sofosbuvir (SOF) for the
treatment of chronic hepatitis C virus (HCV)
infection. The ongoing, open-label trial
evaluated SOF 400mg and the NS5A inhibitor
ledipasvir (LDV) 90mg, with and without
ribavirin (RBV) twice-daily (1,000mg/day or
1,200mg/day), among HCV-infected patient
populations. 100% (n=26/26) of treatmentnaïve
genotype 3 patients receiving 12 weeks
of LDV/SOF plus RBV and 64% (n=16/25)
of treatment-naïve genotype 3 patients
receiving 12 weeks of LDV/SOF without RBV
achieved a sustained virologic response 12
weeks after completing therapy (SVR12).
Among genotype 1-infected patients who
had failed prior treatment with SOF plus RBV,
100% (19/19) achieved SVR12 following 12
weeks of LDV/SOF plus RBV. Additionally, 65%
(n=13/20) of genotype 1-infected patients
with decompensated or Child-Turcotte-Pugh
Class B cirrhosis receiving 12 weeks of
LDV/SOF without RBV achieved SVR12.
The EMA accepted a request for accelerated
assessment for LDV/SOF.
March 17, 2014
Boehringer Ingelheim issued results of a
phase III trial of faldaprevir for the treatment
of 308 hepatitis C (HCV) treatment-naïve
or experienced patients with HCV/HIV
co-infection. Patients were enrolled in either
120mg or 240mg faldaprevir dose groups.
Further, 80% of all patients were eligible
for randomization to a shortened duration
of treatment (24 v. 48 weeks) because they
achieved protocol-defined early treatment
success (ETS). In each faldaprevir dose group,
71% (120mg) and 72% (240mg) of patients
achieved Hepatitis C viral cure 12 weeks
after the conclusion of treatment (SVR12).
SVR12 results were consistent across patients
regardless of HCV genotype-1 subtype (GT1a
or GT1b), presence of compensated cirrhosis,
dose and duration of faldaprevir and
duration of faldaprevir in combination with
pegylated interferon and ribavirin
(PegIFN/RBV). In a post hoc analysis, 75%
of patients with the Q80K variant achieved
SVR12 compared with 71% of patients who
did not have the variant. Serious adverse
events (AEs) were reported in 32 patients
(10%). To date, 24 patients have prematurely
discontinued faldaprevir due to AEs. The
most frequent AEs were nausea (37%),
fatigue (34%), diarrhea (27%), headache (25%)
and weakness (23%). The NDA for faldaprevir
has been accepted for filing by the FDA.
February 10, 2014
AbbVie issued results of four phase III trials
of a fixed-dose combination of ABT-450/
ritonavir (150/100mg) co-formulated with
ABT-267 (25mg), dosed once daily, and
ABT-333 (250mg) with or without ribavirin
(weight-based), dosed twice daily, for the
treatment of chronic genotype 1 (GT1)
hepatitis C virus (HCV) infection. PEARL-II is
a global, multi-center, randomized, openlabel,
controlled study enrolling 179 GT1b
treatment-experienced patients with no evidence
of liver cirrhosis: 91 patients randomized
to the regimen without ribavirin for 12
weeks and 88 patients randomized to the
regimen with ribavirin for 12 weeks. In the
ribavirin-free arm, 100% (n=91/91) of patients
achieved SVR12, while 97% (n=85/88)
achieved SVR12 in the ribavirin-containing
arm. There were no patients who experienced
virologic relapse or breakthrough.
PEARL-III is a global, multi-center, randomized,
double-blind, placebo-controlled study
enrolling 419 GT1b treatment-naive patients
with no evidence of liver cirrhosis: 209
patients randomized to the regimen without
ribavirin for 12 weeks and 210 patients randomized
to the regimen with ribavirin for 12
weeks. 99% receiving the regimen without
ribavirin (n=207/209) and 99% receiving
the regimen with ribavirin (n=209/210)
achieved SVR12. PEARL-IV is a global,
multi-center, randomized, double-blind,
placebo-controlled trial enrolling 305 GT1a
treatment-naive patients with no evidence
of liver cirrhosis: 205 patients randomized
to the regimen without ribavirin for 12
weeks and 100 patients randomized to the
regimen with ribavirin for 12 weeks. 90%
of patients receiving the regimen without
ribavirin (n=185/205) and 97% receiving the
regimen with ribavirin (n=97/100) achieved
SVR12.Virologic relapse or breakthrough
was noted in 8% of patients without ribavirin
and 2% of patients receiving ribavirin.
TURQUOISE-II was completed exclusively in
GT1 cirrhotic patients investigating an alloral,
interferon-free regimen. It is a global,
multi-center, randomized, open-label study
enrolling 380 GT1a and GT1b, treatmentnaive
and treatment-experienced patients
with compensated cirrhosis: 208 patients
randomized to the regimen with ribavirin
for 12 weeks and 172 patients randomized
to the regimen with ribavirin for 24 weeks.
Following 12 weeks of treatment, 92%
of patients (n=191/208) achieved SVR12.
Following 24 weeks of treatment, 96%
of patients (n=165/172) achieved SVR12.
Virologic relapse or breakthrough was noted
in 6% of patients in the 12-week arm and
2% in the 24-week arm. AbbVie is on track to
begin major regulatory submissions early in
the second quarter of 2014.
April 8, 2013
ChronTech issued preliminary results from a phase II trial of ChronVac-C for hepatitis C virus (HCV) infection. This 12-week, open-label study enrolled 29 patients with chronic HCV. Subjects received two monthly vaccinations of ChronVac-C 500ug plus ribavirin and PEG-interferon-a, or placebo plus ribavirin and PEG-interferon-a, administered with Inovio’s MedPulser-DDS electroporation device. At treatment week 12, 71% of the pre-vaccinated group had less than 15 international units of HCV RNA compared to 58% in the non-vaccinated group; 65% were HCV RNA negative compared to 58% in the non-vaccinated group. There were no serious adverse events and the number of patients with moderate adverse events was statistically lower in the pre-vaccinated group than in the non-vaccinated group (p<0.05, Fishers exact test). Based on these data, ChronTech plans to initiate a phase I study of Inovio’s proprietary HCV DNA vaccine later in 2013.
March 18, 2013
Medivir reported interim results from a phase IIa trial of simeprevir for the treatment of hepatitis C virus (HCV). This randomized, open-label study, COSMOS, enrolled 80 subjects with in its first cohort with HCV and mild to moderate fibrosis (METAVIR F0-2). Subjects received simeprevir 150mg and sofosbuvir 400mg daily with or without ribavirin (RBV) for 12 or 24 weeks. Results showed 96.3% in the 12-week arm with RBV and 92.9% in the 12-week arm without RBV achieved SVR8. In the 24-week arms, SVR4 rates with RBV were 66.7% and without RBV 100%. The number of patients reaching this time point was limited, however. The drugs were well tolerated. The most frequent adverse events were fatigue, headache, insomnia and nausea in >10% of patients. Based on these data, Medivir has fully enrolled cohort 2 and will investigate similar regimens and durations in patients with METAVIR scores F3-F4.
March 11, 2013
Boehringer Ingelheim reported interim results from STARTverso 4, a phase III trial of faldaprevir for hepatitis C and HIV co-infection. This randomized, open-label trial enrolled 306 treatment-naive or relapsed subjects with hepatitis C also infected with HIV. The subjects received faldaprevir given for 12 or 24 weeks in combination with PegIFN/RBV given for 24 to 48 weeks. According to re-randomization of Early Treatment Success (ETS), subjects stopped PegIFN/RBV at 24 or 48 weeks or continued PegIFN/RBV until week 48. If no ETS, then subjects received PegIFN/RB for 48 weeks. Data showed 80% of subjects achieved early treatment success (ETS), as defined by the study protocol, when given the regimen that included faldaprevir. Results were consistent across subgroups, regardless of HIV therapy or prior HCV treatment status. Results also were reported from on-treatment virologic response at week 12, which showed 84% of all study subjects had undetectable levels of hepatitis C virus. Three additional phase III trials, part of the HCVerso program, are currently underway.
February 25, 2013
Gilead Sciences issued results from a phase III trial of nucleotide sofosbuvir plus ribavirin (RBV) in chronic hepatitis C virus (HCV). This randomized study, FUSION, enrolled treatment-experienced patients with genotype 2 or 3 chronic HCV infection who failed prior treatment. Subjects received either a 12-week (n=103) or 16-week (n=98) course of sofosbuvir 400mg/day plus RBV (1,000mg/day or 1,200mg/day). The study met its primary efficacy endpoint of superiority compared to a predefined historic control sustained virologic response (SVR) rate of 25%. In FUSION, 50% of patients (n=50/100) in the 12-week arm and 73% of patients (n=69/95) in the 16-week arm achieved SVR12 (p<0.001 for both arms). In the 12-week arm, SVR12 rates were 86% among genotype 2 and 30% among genotype 3 patients. In the 16-week arm, SVR12 rates were 94% among genotype 2 and 62% among genotype 3 patients. Among the 34% of FUSION participants who had compensated cirrhosis at baseline, 31% achieved SVR12 in the 12-week arm, and 66% achieved SVR12 in the 16-week arm. All patients in the study became HCV negative on treatment, and relapse accounted for all virologic failures. The drug was well tolerated. The most frequent adverse events were fatigue, headache, insomnia and nausea. Based on these data plus results from three other phase III studies, Gilead is on track to file regulatory applications in the U.S. and Europe in the second quarter.
February 11, 2013
Gilead Sciences released results from a phase III study of nucleotide sofosbuvir in combination with ribavirin (RBV) for the treatment of chronic hepatitis C virus (HCV) infection. This 12-week, randomized study, FISSION, enrolled 496 treatment-naïve patients with genotype 2 or 3 HCV infection. Subjects received a 12-week course of sofosbuvir 400mg once daily plus RBV 1,000mg or 1,200mg/day, or standard of care with 24 weeks of pegylated interferon alfa-2a (pegIFN) 180 Î¼g/week plus RBV 800mg/day. The study met its primary efficacy endpoint of non-inferiority of sofosbuvir plus RBV to pegIFN plus RBV, with 67% of patients achieving a sustained virologic response (SVR) in the sofosbuvir plus RBV treatment group versus 67% in the peg-IFN plus RBV treatment group (95% CI for the difference: -7.5% to +8.0% for sofosbuvir plus RBV versus pegIFN plus RBV; redefined criterion for noninferiority was a lower bound of a two-sided 95% CI of -15%). The most frequent adverse events were fatigue, headache, nausea, insomnia and dizziness. Gilead Sciences plans to present this data, along with three other phase III studies of sofosbuvir plus RBV for HCV, at a future scientific conference.
January 21, 2013
Achillion Pharmaceuticals issued interim results from a phase IIa trial of ACH-3102 in combination with ribavirin for the treatment of patients with hepatitis C virus (HCV) infection. This open-label, pilot study enrolled eight treatment-naïve patients with chronic genotype 1b (GT 1b) HCV (IL28b genotype CC). Subjects received 225mg of ACH-3102 on day one followed by 75mg of ACH-3102 once daily on subsequent days, in combination with 1000mg-1200mg dose of ribavirin for 12 weeks. To date, results show treatment with ACH-3102 has resulted in rapid reduction in HCV RNA accompanied by normalization of liver enzymes. ACH-3102 has been well tolerated. There have been no serious adverse events, treatment discontinuations or on-treatment viral breakthrough reported to date. Based on these data, Achillion Pharmaceuticals will continue the phase IIa trial and plans to expand enrollment in the study to include non-CC GT 1b treatment-naïve patients during the first quarter of 2013, pending regulatory discussions.
December 3, 2012
Gilead Sciences released results from a phase III trial of sofosbuvir plus ribavirin (RBV) for the treatment of genotype 2 or 3 chronic hepatitis C virus (HCV) infection. This randomized, placebo-controlled study, POSITRON, enrolled 378 patients with genotype 2 or 3 chronic HCV infection who are not candidates to take interferon. Subjects received sofosbuvir 400mg once daily plus weight-based RBV twice daily (n=207), or matching placebo (n=71). Data demonstrated 78% of patients (n=161/207) remained HCV RNA undetectable 12 weeks after completing therapy (SVR12). The safety profile of sofosbuvir was similar to that observed in previous studies, and there were few treatment discontinuations due to adverse events. In the small percentage of patients with cirrhosis at baseline who received sofosbuvir/RBV, 61% achieved SVR12. All patients receiving sofosbuvir/RBV became HCV RNA negative on treatment and relapse accounted for all virologic failures, while no patient in the placebo group achieved an SVR12. The drug was well tolerated. The most frequent adverse events were fatigue, nausea, headache, insomnia, pruritis and anemia. Based on these data, Gilead Sciences expect to submit its first regulatory filings for sofosbuvir by mid-2013.
November 19, 2012
Merck released results from a phase II trial of MK-5172 for the treatment of chronic hepatitis C virus (HCV). This multi-center, double-blind, randomized, active-controlled, dose-ranging study enrolled 332 treatment-naïve patients with HCV genotype 1 infection. Subjects received MK-5172 100mg QD, 200mg QD, 400mg QD or 800mg QD in combination with peginterferon alfa-2b 1.5μg/kg weekly and ribavirin 600-1,400mg QD for 12 weeks. Subjects then received only peginterferon and ribavirin regimens for another 12 or 36 weeks, depending on response to treatment. Subjects in the active-control group received a four-week lead in with peginterferon and ribavirin regimens, followed by a regimen of boceprevir. Results showed the MK-5172 regimens had rates of the complete early viral response (cEVR) that ranged from 82.8% to 93%, versus the control rate of 74.2%. Of the patients randomized to the MK-5172 arms, 2.3% met the protocol-defined criteria for virologic failure: one patient was re-infected with genotype 3 infection; and four patients had no detectable (n=3) or low (n=1) levels of MK-5172 at time of failure and for a period of time prior. The drug was well tolerated. The most frequent adverse events were elevation of ALT/AST levels.
August 13, 2012
Achillion Pharmaceuticals issued results from a phase II trial of >strong>sovaprevir in combination with pegylated interferon and ribavirin for the treatment of hepatitis C virus (HCV). This randomized, combination, dose-escalation study enrolled 58 patients with genotype 1 HCV. Subjects received 200mg, 400mg or 800mg of sovaprevir once daily, as well as pegylated interferon and ribavirin (P/R) for 12 weeks, followed by an additional 12 or 36 weeks of P/R. The data showed positive sustained viral response (SVR4) results: 90% in the 200mg dose group, 85% in 400mg and 100% 800mg. Sovaprevir was well tolerated in all dose groups. The most frequent adverse events were consistent with P/R treatment. Based on these data, Achillion plans on moving to combination studies of and ACH-3102, another of their novel drugs, by the end of the year.
August 16, 2010
Vertex released positive results from a phase III trial evaluating telaprevir for hepatitis C. This open label, randomized study, ILLUMINATE, was designed to evaluate whether there is benefit to extending therapy from 24 to 48 weeks in patients with undetectable HCV at weeks four and 12 of treatment (extended rapid viral response or eRVR). The trial enrolled 540 treatment nave subjects with chronic HCV genotype 1. Those who met the eRVR criteria and who remained on treatment were randomized at week 20 to receive 24 or 48 weeks of total treatment. The primary endpoint was non-inferiority with respect to SVR rates in the 24 and 48-week treatment arms. This endpoint was reached. Sustained viral response rates of 92% and 88% were observed in the 24 and 48-week treatment groups, respectively. The relapse rates were 5.7% and 1.9%, respectively.
December 4, 2006
Dynavax announced positive results from a phase III trial of Heplisav for the treatment of Hepatitis B. This trial enrolled 400 seronegative subjects who received three doses of the Heplisav vaccine or three doses of Engerix-B, an approved Hepatitis B vaccine. The primary endpoint of the trial was seroprotection four weeks after the third immunization. Results revealed that, after three doses, Heplisav provided seroprotection to 100% of subjects while Engerix-B provided seroprotection to 73.1% (p < 0.0001). The greatest deviation in seroprotection was observed in the subjects aged 56 to 70 years where Heplisav provided 100% seroprotection and Engerix-B provided 56.1% seroprotection. Dynavax plans to initiate phase III trials to investigate a two dose regimen of Heplisav versus Engerix-B by late 2006 to early 2007.
September 5, 2006
Targeted Genetics released positive interim data from a phase I trial of tgAAC09, a potential HIV vaccine candidate based on recombinant adeno-associated virus vector serotype 2 (AAV2). This double-blind, placebo-controlled, dose-escalation study enrolled 50 subjects in Germany and Belgium and 30 subjects in India, all of who were healthy and HIV-negative. Each subject received a single intramuscular injection into the upper arm. A subset group also received a second dose of tgAAC09 to determine if repeat dosing is safe and boosts immune responses. The vaccine was determined to be safe and well tolerated at both dosing levels. Additionally, moderate immune responses were observed in the subset group who received the highest dose. A phase II trial of tgAAC09 is currently underway in South Africa, Uganda and Zambia.
ViroPharma and Wyeth reported positive preliminary data from a phase Ib trial of HCV-796, combined with pegylated interferon alfa-2b, for the treatment of hepatitis C. This randomized, double-blind, placebo-controlled, sequential-group study of ascending multiple doses enrolled 16 treatment naïve subjects with chronic hepatitis C infections. Subjects received HCV-796 or placebo (100 mg, 250 mg, 500 mg or 1000 mg) every 12 hours, for 14 days. On days 1 and 7 this was combined with peglyated interferon alfa-2b (1.5 ug/kg/dose). Safety data revealed no dose limiting toxicities. Efficacy data after 14 days of treatment determined that, across all dose groups, the combination of HCV-796 and pegylated interferon produced a mean viral reduction of between 3.3 and 3.5 log10 (99.95% to 99.97%) compared to 1.7 log10 with pegylated interferon alone. Based on these results, ViroPharma and Wyeth planned to initiate a phase II trial of HCV-796 at 500 mg to determine further dose response.
May 8, 2006
Alnylam reported positive results of a pair of phase I trial of ALN-RSV01, for the treatment of respiratory syncytial virus infections at the 2006 Pediatric Academic Societies' Annual Meeting in San Francisco. The double-blind, placebo-controlled, randomized studies enrolled a combined 101 subjects (34 in the US, 67 in Europe), who received single (1.5, 5, 15, 50, or 150 mg) or multiple (5, 25, and 150 mg daily for 5 days) doses of the drug or saline placebo via nasal spray. Primary safety data were generally positive, with no serious adverse events reported and an overall adverse event rate comparable to placebo. No evidence of laboratory abnormalities or electrocardiographic complications was noted. Pharmacokinetic data indicated no significant systemic exposure to the drug following intranasal administration.
Human Genome Sciences issued interim results of an ongoing phase II trial of Albuferon, for the treatment of treatment-experienced HCV infections. This randomized study had treated 71 patients to date, who received one of three doses of Albuferon (900 mcg every 14 days, 1200 mcg every 14 days, or 1200 mcg every 28 days) plus weight-based oral ribavirin (500 mg or 600 mg twice daily). 63% (n=45/71) of subjects had previously now responded to treatment with pegylated interferon alpha, and 93% (n=66/71) were infected with genotype 1 HCV. Pooled trial data indicated that 31% (n=22/71) of subjects (all treatment groups) achieved undetectable HCV RNA load at 48 weeks. Follow-up data from 12 weeks after the conclusion of treatment indicated that 20% of subjects maintained undetectable HCV RNA levels. Antiviral activity was similar between the 14 and 28 day 1200 mcg groups.
Pharmasset and Bukwang announced preliminary results pf a phase III trial, dubbed Study 303, of clevudine for the treatment of hepatitis B (HBV) infections. This late-stage study had treated 55 treatment-naïve patients to date at sites in Korea; 40 subjects were hepatitis B e antigen positive (HBeAg+) and 15 were HBeAg-. All subjects received 30 mg of the drug daily for 24 weeks, followed by 10 mg daily for a 24-week maintenance period. At 48 weeks 68% of HBeAg+ and 100% of HBeAg- patients achieved HBV DNA levels <300 copies/ml (PCR negative), and 89% and 100% of patients (respectively) achieved normal alanine aminotransferase levels (a measure of liver function). Further 16% experienced loss of serum HBeAg, and HBeAg seroconversion occurred in 14% of HBeAg+ patients. No serious adverse events were reported.
Roche issued positive results of a phase I trial of R1626, for the treatment of hepatitis C (HCV) infections. This randomized, placebo-controlled study had enrolled 18 subjects to date, who received one of two doses of the drug (500 mg or 1500 mg) or placebo twice daily for 14 days, with a 14 day follow-up. This higher trial dose produced a mean reduction in serum HCV RNA level of 1.2 log10, a clinically significant result. Both doses of the drug were well tolerated, with no serious adverse events reported and no early withdrawals from the trial. The trial was ongoing, including higher dose regimens of the drug.
May 1, 2006
Biolex and OctoPlus have issued positive results of a phase I trial of Locteron, for the treatment of chronic hepatitis C infections, at the European Association for the Study of Liver Disease meeting in Vienna. This randomized, double-blinded, placebo-controlled study enrolled 27 healthy volunteers in The Netherlands, who received three escalating doses of Locteron or the approved pegylated interferon drug PEG-INTRON. Trial data yielded a positive safety and tolerability profile, with reductions in frequency and severity of flu-like symptoms following dosing relative to the approved treatment. Pharmacokinetic data were supportive of dosing every two weeks, and administration of the drug yielded a linear release profile, without a front-end "burst effect." Changes in biomarkers associated with interferon activity were also noted, at levels equal or greater to those noted with PEG-INTRON.
Transgene issued positive results of a phase II trial of TG4001, for the treatment of high-grade cervical intraepithelial neoplasia (CIN2/3) associated with HPV-16 infections, at the Eurogin 2006 Congress in Paris. 6-month data yielded preliminary evidence of efficacy, with 55% of evaluable subjects (n=10/18) achieving normal colposcopy, 50% (n=9/18) yielding no CIN2/3, and 50% (n=9/18) achieving a complete elimination of HPV16 E6/E7 mRNA. No serious adverse events were associated with treatment. This open-label study enrolled 21 CIN2/3 patients across 9 sites in France, who received 3 subcutaneous injections of the vaccine (5.107 pfu).
March 27, 2006
AnorMED issued positive results of a clinical trial, dubbed XACT, of their investigational HIV-entry inhibitor AMD070 for the treatment of HIV infections. Preliminary data from the first dosing cohort yielded positive initial efficacy, with 50% of subjects (n=4/8) experiencing significant reductions in CXCR4 viral load. Mean viral load reduction was 1.3 log. These results were considered sufficiently positive to allow initiation of enrollment and dosing in higher-dose cohorts. This open-label study planned to enroll a total of 48 patients across 4 dosing cohorts. Additional results were expected at the ICAAC annual meeting in September 2006, and the company anticipated initiating a phase IIb trial of the drug before the end of 2006.
Coley Pharmaceutical announced positive interim results of a clinical trial of Actilon (CPG 10101) for the treatment of hepatitis C (HCV) infections. Top-line results indicated that 86% (n=12/14) of subjects receiving the drug plus control therapy achieved an early viral response (>2 log reduction in serum HCV RNA levels at 12 weeks), vs. 57% (n=8/14) for control therapy alone. Further, Actilon-plus-control produced a mean HCV RNA reduction of 3.3 log at 12 weeks, vs. 2.2 log for control alone. The drug was generally well tolerated, with similar adverse events seen in both groups. This randomized, controlled study enrolled a total of 74 HCV patients, who received approved control treatment with pegylated interferon and/or ribavirin alone or in combination with Actilon. Additional results from the study were to be presented at the upcoming European Association for the Study of the Liver meeting in Vienna in April 2006.
Valeant issued negative results of a phase III trial, dubbed VISER1, of Viramidine (taribavirin) for the treatment of HCV infections. Study data failed to meet their primary non-inferiority endpoint of sustained viral response: 38% of patients in the intent to treat population achieved an SVR, compared to 52% for approved therapy with ribavirin. Secondary efficacy was established, with statistical non-inferiority established in a per-protocol analysis of patients in North America and Europe (51% vs. 56%, respectively), and in patients weighing a maximum of 75 kg (62% vs. 60%). Safety data were generally positive, and Viramidine produced significantly fewer episodes of anemia than the approved drug, the trial's primary safety endpoint (5% vs. 24%; p<0.0001). This randomized, double-blind, controlled, parallel-group study enrolled 970 treatment-naïve patients at sites in the US, Canada, Europe, Israel, New Zealand and Australia. Subjects received either a fixed dose of 600 mg Viramidine, or a weight based 1,000/1,200 mg regimen of ribavirin, all in combination with peginterferon alfa 2b, for 24 to 48 weeks (based on viral genotype). The company indicated that the drug was on track for NDA filing by the end of 2007.
October 31, 2005
Biolex has announced positive results of a phase I trial of BLX-883, their recombinant formulation of interferon alpha, for the treatment of hepatitis C. Safety data yielded no serious adverse events, and overall drug-related adverse events for BLX-883 and Intron A (an approved formulation of interferon alpha) were comparable. Bioactivity and immunogenicity data were also comparable. This open-label controlled study enrolled 24 subjects in the US and UK, who received one of three doses of BLX-883; the 12 subjects receiving a dose of 3 million IU also received 3 million IU Intron A.
Tanox reported positive results of a phase II trial of TNX-355, their investigational viral entry-inhibitor for the treatment of HIV infections. Study results indicated that the lower treatment level of the drug, in combination with background therapy, produced a viral load reduction of 1.16 log10, compared to 0.02 log10 for background therapy alone, in last-observation-forward analysis (p<0.001). Significance was also reached in reduction from baseline values for the combination (1.19 log10) vs. background alone (0.32 log10; p=0.002). Mean maximum reduction over the 24 week period was 1.97 log10 (p=0.002). Secondary data indicated that 56% of subjects achieved a viral-load reduction of at least 0.5 log10, and 44% achieved a reduction of at least 1.0 log10, at week 24, indicating a durable response. Mean CD4+ cell counts increased in both study arms, though the difference was non-significant between the drug and placebo. This ongoing randomized, placebo controlled study enrolled 82 tripled-class treatment-experienced HIV-1-positive patients, who were randomized 1:1:1 to receive 10 mg/kg, 15 mg/kg or placebo every 2 weeks, in addition to optimized background therapy, for 24 weeks. Treatment in this study was scheduled to continue through 48 weeks, with projected phase III initiation in 2006.
October 10, 2005
Merck reported positive results of their phase III "FUTURE II" trial of Gardasil, their quadrivalent human papillomavirus (HPV) vaccine for the prevention of HPV-associated cervical cancers, at the Infectious Diseases Society of America Annual Meeting. Trial data have yielded evidence of efficacy, with the vaccine preventing 100% of cases of high-grade cervical intraepithelial neoplasia and non-invasive cervical cancers associated with HPV strains 16 and 18, compared to 21 cases in the placebo group (p<0.001). Furthermore, all subjects receiving the vaccine remained free of detectable HPV 16/18 infections through 7 months. Secondary efficacy data, which considered a broader patient cohort that included potential protocol violators and patients who may have become infected with HPV during the vaccine course, yielded a 97% reduction in lesion risk, with 1 case in the treatment group vs. 36 for placebo. The most common drug- related adverse event was injection site discomfort. This prospective, randomized, double-blind, placebo-controlled study enrolled 12,167 women across 90 sites in 13 countries, who received three doses of Gardasil (n=6082) or placebo (n=6075) over 6 months, and who were then followed for an average of 2 years. Results of this trial were to be included in the BLA for the drug, scheduled to be filed in Q4 2005.
Vertex Pharmaceuticals has issued positive results of a clinical trial of their hepatitis C virus (HCV) protease inhibitor VX-950, for the treatment of chronic HCV infections. These data were presented at the 12th International Symposium on Hepatitis C and Related Viruses in Montreal. Results from the study indicated that the drug reduced median serum alanine aminotransferase (ALT) levels after 14 days of treatment, with decreases of 25-32 U/L for all treatment arms (n=18), compared to a decrease of 8 U/L for placebo (n=6). These reductions corresponded to 83% of subjects with elevated ALT levels at baseline achieving normalization by day 14, compared to 0% for placebo. These reductions may indicate reductions in HCV-related liver damage. This placebo-controlled study enrolled 24 subjects, who received one of three doses of the drug or placebo for 14 days. Based on these results, Vertex re-affirmed its plans to initiate a phase Ib trial of the drug in Europe and to file an IND for the drug in the US in Q4 2005, to support initiation of phase II trials before year's end.
May 16, 2005
Vertex Pharmaceuticals issued interim results of a phase Ib trial of VX-950, their investigational protease inhibitor for the treatment of hepatitis C virus (HCV) infections. Data from the ongoing study indicated that the drug yielded significant antiviral activity, with subjects experiencing a median reduction in genome 1 HCV RNA of greater than 3 log10 within three days of treatment; subjects receiving 750 mg thrice daily achieving an additional median reduction greater than 4 log10 over days 3-14. This double-blind, randomized, placebo-controlled study enrolled 34 HCV patients across 3 European sites, and was designed to investigate the tolerability, pharmacokinetics, effect on viral kinetics, and optimum dosing regimen of the drug. Subjects received one of 3 oral doses of VX-950 (450 mg or 750 mg every 8 hours, or 1250 mg every 12 hours) or placebo for 14 days. The company announced plans to release more detailed results at the Digestive Disease Week conference on May 17.
January 24, 2005
ALK-Abello has reported positive preliminary results of their “GT-07” trial of their sublingual grass-pollen immunotherapy tablet, for the prevention of rhinoconjunctivitis (hay-fever). Trial data met their primary efficacy endpoint, producing a 37% reduction in symptoms of rhinoconjunctivitis and a 41% reduction in the need for additional medication, vs. placebo. The drug was also found to be safe and well tolerated. This double-blind, placebo-controlled, multi-centre study enrolled 114 patients with moderate-to-severe rhinoconjunctivitis and grass pollen induced mild-to-moderate asthma in Sweden and Denmark. Subjects were randomized to receive either the tablet or placebo once daily for at least 10 weeks.
Genentech has reported positive final results of a phase III extension study of their approved humanized monoclonal antibody Raptiva (efalizumab), for the treatment of moderate to severe plaque psoriasis. Results indicated that the drug produced demonstrated improved efficacy at 24 weeks vs. 12 in a number of clinical outcomes, including improvements in the portion of subjects achieving PASI-75 severity score improvement levels (43.8% vs. 26.6%), PASI-50 (66.6% vs. 58.5%). Furthermore, the percentage of patients who achieved a sPGA rating of minimal or clear increased from 25.7% at 12 weeks to 35.9% at 24, and the mean percentage of improvement in all patient-reported outcomes was maintained at week 24. Overall reported adverse events also declined during the extension (from 80.4% to 63.2%). This 12-week, 516-patient open-label extension followed a 12-week, 556-patient, double-blind, placebo-controlled parallel-group study, which investigated once-weekly subcutaneous dosing of 1 mg/kg Raptiva or placebo.
Valeant Pharmaceuticals has issued positive results of a phase II trial of its oral guanosine analog Viramidine, for the treatment of Hepatitis C. Preliminary analysis of trial data has indicated that the trial met its primary efficacy endpoint, demonstrating non-inferiority of Sustained Viral Response (SVR) for the 600 mg. BID dose of Viramidine, compared with ribavirin (an approved treatment), at both the end of treatment (24 or 48 weeks) and after an additional 24 week follow-up. Furthermore, the drug produced a significantly lower rate of anemia than the approved therapy (4% vs. 27%; p<0.001), and incidence of all other adverse events was similar between drugs. This active-controlled proof of concept study enrolled a total of 180 treatment-naïve patients with chronic HCV, who were randomized to receive one of three BID regimens of Viramidine (400 mg, 600 mg, or 800 mg) or standard therapy with ribavirin (1,000/1,200mg daily). Subjects were treated for 24 or 48 weeks, based on viral genotype analysis, and then enrolled in a 24 week extension study. Based on these results, Valeant has announced plans to use the 600 mg BID regimen of the drug in phase III trials.
November 29, 2004
Panacos Pharmaceuticals reported preliminary results of a phase I/II proof-of-concept trial of PA-457, their viral maturation inhibitor under investigation for the treatment of HIV infections. Single doses of the drug produced preliminary evidence of efficacy, with a significant reduction in viral load (as measured by plasma viral RNA concentrations) of as much as 0.7 log10 at higher doses, compared to baseline. This pharmacokinetic and efficacy study randomized HIV-positive subjects not currently on other therapies to receive dose-ranging single doses of the drug or placebo. Panacos announced plans to initiate a multiple-dose phase IIa trial of PA-457 as once-daily monotherapy in HIV-positive subjects not on other therapy in the first half of 2005, based upon these results.
Rigel Pharmaceuticals has announced negative results of a phase I/II trial of R803, their investigational RNA polymerase inhibitor for the treatment of hepatitis C (HCV) infections. The trial failed to meet its primary endpoint, a reduction in viral load relative to baseline, though a minor trend towards improvement was seen. The company noted that R803 had exhibited poor oral bioavailability, with mean serum drug concentration reaching minimum therapeutic levels for only a few hours during the daily dosing regimen. The drug did meet all safety and tolerability endpoints, with no serious adverse events. The randomized, placebo-controlled, double-blind multiple, dose-escalating safety and pharmacokinetic study enrolled 32 HCV patients at 2 US sites, who were randomized into one of eight dosing cohorts. Rigel announced plans to continue development of the drug in a new formulation.
November 8, 2004
Anadys Pharmaceuticals has reported positive results of a phase I b trial of isatoribine, a Toll-like receptor 7 agonist for the treatment of chronic hepatitis C (HCV) infections. Trial data indicated that the drug was biologically active, with significant changes in interferon-alpha-mediated disease markers, and produced a significant 82% reduction in serum viral load after seven days at the highest dosing regimen. Treatment was also observed to be safe and well tolerated, with no discontinuations or regimen changes due to adverse events. This dose escalating, open-label study enrolled a total of 32 adult HCV patients across 2 European centers into one of four seven-day dosing regimens (200 mg, 400 mg, 600 mg or 800 mg daily). Anadys announced that the trial would serve as the basis for upcoming trials of their investigational isatoribine pro-drug ANA975.
Inhibitex reported positive results of a phase I trial of their investigational anti-microbial monoclonal antibody Aurexis, for the adjuvant treatment of serious Staphylococcus aureus (S. aureus) infections, at the 44th annual Interscience Conference on Antimicrobial Agents and Chemotherapy. Trial results showed Aurexis was generally safe and well-tolerated by the study participants, and had an elimination half life of Aurexis was approximately 21 days. This open-label, dose-escalating trial enrolled 19 healthy patients who receive one of four dose levels of Aurexis. The company announced that they expected to use these findings to support ongoing enrollment efforts in their phase II trial of the drug plus standard antibiotic therapy in patients with hematological S. aureus infections.
Microscience issued positive results of a phase I trial of their oral hepatitis B (HBV) vaccine spi-VECTM. Study data met their primary safety endpoint, with no significant adverse events noted. Further, the drug was shown to be significantly immunogenic, with all subjects generating a T-cell response to hepatitis B core antigen (HBcAg), and 95% subjects in the high-dose group exhibited an immune response marked by the gamma interferon secretion and IL-5 down-regulation in stimulated T-cells. This type of immune response is known to promote viral clearance in chronic HBV infections. This open-label dose-escalating study enrolled 30 healthy volunteers, who received two single escalating oral doses of the vaccine 56 days apart. Microscience announced that they were planning phase II trials for spi-VECTM, based upon these results.
Theravance has reported results from a phase II study of their investigational antibiotic telavancin (TD-6424), for the treatment of Gram-positive skin and skin structure infections (cSSSI). Results indicated that the drug demonstrated comparable efficacy and improved dosing options than standard therapy. Specifically, the drug produced statistically non-distinct cure rates in patients with cSSSIs, including an 82% cure rate among the subset of patients with cSSSIs caused by methycillin-resistant S. aureus infections (vs. 69% for standard therapy with vancomycin), and the minimum inhibitory concentration were lower for telavancin than vancomycin for all S. aureus strains. This exploratory standard-therapy-controlled safety and efficacy trial enrolled a total of 167 subjects with cSSSIs. These data will be used to support ongoing phase III studies of the drug.<
October 11, 2004
Peninsula Pharmaceuticals and Takeda Chemical Industries issued positive results of a phase I trial of PPI-0903, its investigational cephalosporin antibiotic for Gram-positive soft complicated skin and skin-structure infections, and hospital- and community-acquired pneumonias. Preliminary data analysis indicates that the drug was generally safe and well tolerated in both single and multiple dose regimens. Adverse events were transient and mild, no serious adverse events were observed, and no subjects withdrew during the trial. This open-label, sequential dosing regimen study enrolled a total of 14 healthy volunteers, who received escalating single intravenous doses of PPI-0903, followed by an escalating multi-dose regimen of intravenous doses for up to 14 days.
Valeant Pharmaceuticals announced positive end-of treatment data from their phase II study of viramidine for the treatment of Hepatitis C (HCV). These preliminary results indicated that treatment with viramidine demonstrated non-inferior efficacy to ribavirin, an approved HCV therapy at all trial doses, as measured by the percentage of patients with undetectable HCV RNA levels. Furthermore, viramidine produced significantly fewer instances of anemia at all doses (4% vs. 27%, p<0.001), compared with ribavirin; this included no subjects at the lowest dose and only 2% of subjects at the middle dose. The open-label, randomized, active-control, multi-center study enrolled a total of 180 treatment-naïve HCV subjects, who received standard therapy with peginterferon alfa-2a, plus one of three oral regimens of viramidine (400 mg, 600 mg or 800 mg twice daily), or ribavirin (1000/1200 mg daily). Analysis of the data from this trial, as well as two phase III clinical trials of the drug, are ongoing.
November 3, 2003
Genzyme reported positive preliminary results from a phase II trial investigating tolevamer sodium, a polymer therapy for the treatment of Clostridium difficile associated diarrhea (CDAD). Results showed that 22% of subjects taking vancomycin experienced recurrence of CDAD, while 19% taking tolevamer (6g) recurred. Data showed the study reached the primary endpoint of non-inferiority to vancomycin with respect to time to resolution of diarrhea. Tolevamer was found to be similar to vancomycin in median days to resolution of diarrhea and demonstrated a risk ratio relative to vancomycin of 0.98. The randomized, double blind, active-controlled study trial enrolled 289 subjects at 58 sites in the U.S. Canada and the United Kingdom. The study was designed to determine the safety and effectiveness of tolevamer capsules at two dose levels (6g & 3g), versus vancomycin.
Idenix Pharmaceuticals and the University of Hong Kong reported positive results from a phase IIb trial investigating telbivudine (L-deoxythymidine or LdT), a selective nucleoside for the treatment of hepatitis B virus (HBV). Results showed that telbivudine achieved significantly better suppression of HBV compared to lamivudine monotherapy, the current standard of care. Subjects receiving telbivudine achieved an average reduction in viral load of one million fold. The randomized, double-blind, international study enrolled 104 treatment-naive subjects with HBV. Results were reported at the 54th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston.
June 9, 2003
Access Pharmaceuticals reported positive results from a phase III trial investigating OraDisc A, drug releasing patch for the treatment of canker sores. Results demonstrated a statistically significant enhancement in the primary clinical endpoint, complete healing by day five. The randomized, placebo controlled study enrolled 604 subjects who were divided into three groups. In total, 303 subjects were treated with OraDisc A, which contains the active ingredient amlexanox, 301 subjects received a placebo disc and 97 subjects received no treatment. The full statistical analysis of this study has not been completed. The company plans to file for approval in the U.S. and Europe in the coming months.
InterMune reported positive interim data from a phase IV trial investigating Infergen (interferon alfacon-1) for the treatment of chronic hepatitis C infection. Results demonstrated that more than half (52%) of the subjects have responded to the treatment. At week 8, an antiviral response in serum was observed in 20% (6/30) and 27% (8/30) of subjects treated with the daily dosing and induction dosing regimen, respectively. At week 24, an antiviral response was observed in 40% (10/25) and 52% (14/25). Both the daily dosing and induction dosing regimens were found safe and moderately well tolerated. Adverse events included myalgia, fatigue and headache. The randomized, open-label trial was conducted in 50 chronic hepatitis C subjects who were non-responders to prior combination therapy with pegylated interferon and ribavirin. The trial will continue with combination therapy for an additional 24 to 64 weeks. Results were reported at the Digestive Disease Week 2003 conference in Orlando, Florida.
January 14, 2002
Positive results were reported from a phase I trial of ACH-126,443 (beta-L-Fd4C), an L-nucleoside analog with in vitro activity against chronic hepatitis B and human immunodeficiency virus. The trial was designed to evaluate six dose levels of the drug in healthy subjects. Pharmacokinetic results demonstrated ideal absorption of the compound into the bloodstream, and the data supports once daily dosing. ACH-126,443 is being developed by Achillion Pharmaceuticals.
Statistically significant preliminary results were reported from an ongoing phase III trial of Corixa's RC-529 synthetic adjuvant in combination with Rhein Biotech's hepatitis B vaccine. The trial was designed to compare vaccination with the hepatitis B vaccine plus the RC-529 adjuvant to vaccination with the vaccine alone in healthy adults who were not immune to hepatitis B virus (HBV). A total of 285 subjects received at least one vaccination, and 272 of these subjects were evaluated for efficacy. Results showed that there were significantly more subjects seroprotected after two immunizations with the hepatitis B vaccine plus RC-529 than with the vaccine alone (95.5% versus 82.1%). Analysis of secondary efficacy endpoints, such as seroconversion rates at days 30 and 60, also showed a statistically significant benefit in favor of the RC-529/vaccine combination.