October 16, 2017
Janssen Pharmaceutical announced results
from the pivotal phase III EMERALD study. The
study demonstrated that switching to the investigational
single-tablet regimen (STR) containing
darunavir 800mg, cobicistat 150mg, emtricitabine
200mg and tenofovir alafenamide 10mg
(D/C/F/TAF) was non-inferior to continuing treatment
with a boosted protease inhibitor (PI) plus
emtricitabine and tenofovir disoproxil fumarate
in human immunodeficiency virus type 1 (HIV-1)
positive, virologically suppressed adults. The
study was a randomized (2:1), open-label, international,
multicenter, parallel-group, non-inferiority,
48-week study in adult HIV-1 infected patients
who are virologically suppressed (viral load [VL]
<50c/mL for two months and had no more than
one VL 50c/mL and <200 c/mL allowed within 12
months before screening). 1,141 patients were
randomized and treated as follows: D/C/F/TAF
(n=763); control (n=378). Inclusion criteria to be
enrolled in the trial included absence of history
of virologic failure on darunavir, and if historical
genotype was available, absence of darunavir
RAMs. Through 48 weeks, cumulative virologic
rebound was 2.5% (D/C/F/TAF, n=19) vs. 2.1%
(control, n=8) with 12/19 in D/C/F/TAF and 4/8
in the control group re-suppressed (<50 c/mL)
by the end of the evaluation period. Additionally,
at week 48, virologic suppression was 94.9%
(D/C/F/TAF) and 93.7% (control), and virologic
failure occurred in 0.8% and 0.5%, respectively,
with no discontinuations for virologic failure and
no observed RAMs to any study drug through 48
weeks. An NDA was filed on September 22, 2017,
to the FDA.
October 9, 2017
Gilead Sciences announced detailed 48-week results from a phase III study (Study 1878) evaluating the efficacy and safety of switching virologically suppressed HIV-1 infected adult patients from a multi-tablet regimen containing a boosted protease inhibitor (bPI) to a fixed-dose combination of bictegravir (50mg) (BIC) and emtricitabine/tenofovir alafenamide (200/25 mg) (FTC/TAF). In Study 1878, a total of 577 virologically suppressed adults with HIV taking regimens of boosted atazanavir (ATV) or darunavir (DRV) + abacavir/lamivudine (ABC/3TC) or FTC/tenofovir disoproxil fumarate (TDF) were randomized 1:1 to continue their bPI regimen or to switch to open-label coformulated BIC/FTC/TAF once daily. At the primary endpoint of week 48, switching to BIC/FTC/TAF was non-inferior to continuing on a bPI regimen with 1.7% of patients in each group having HIV-1 RNA =50 c/mL (difference: 0.0%, 95% CI: -2.5% to 2.5%, p=1.00); the proportion of patients with HIV-1 RNA <50 c/mL was 92.1% in the BIC/FTC/TAF arm and 88.9% in the bPI arm, according to FDA snapshot algorithm. No patients in the BIC/FTC/TAF arm developed treatment-emergent resistance, and one participant on DRV/ritonavir + ABC/3TC developed a treatment-emergent NRTI mutation associated with abacavir. No renal adverse events leading to discontinuations or cases of proximal renal tubulopathy occurred with BIC/FTC/TAF. The incidence of grade three or four adverse events was 4% (n=13) for the BIC/FTC/TAF arm versus 6% (n=18) for the bPI arm; the incidence of grade three or four laboratory abnormalities was 16% (n=45) for the BIC/FTC/TAF arm versus 29% (n=83) for the bPI arm. The most commonly reported adverse events (all grades) in both arms included headache, diarrhea, nasopharyngitis and upper respiratory tract infection. Gilead filed a New Drug Application for BIC/FTC/TAF with a Priority Review voucher on June 12, 2017, and the FDA set a target action date of February 12, 2018, under the Prescription Drug User Fee Act. A marketing application for BIC/FTC/TAF is also under review in the European Union and was validated by the EMA on July 13.
February 27, 2017
Gilead Sciences reported 144-week data from two phase III studies (Studies 104 and 111) evaluating the safety and efficacy of Genvoya (elvitegravir 150mg, cobicistat 150mg, emtricitabine 200mg and tenofovir alafenamide 10mg) for the treatment of HIV-1 infection in treatment-naïve adults. In the combined analysis, a total of 1,733 treatment-naïve adults with HIV were randomized to receive either Genvoya or Stribild. At week 144, 84.2% (n=729/866) of patients taking Genvoya and 80% (n=694/867; 95% CI: 0.6% to 7.8%, p=0.021) of patients taking Stribild achieved HIV-1 RNA levels less than 50 copies/mL. Additionally, at week 144, 81.1% (n=702/866) of patients taking Genvoya and 75.8% (n=657/867; 95% CI: 1.5 to 9.2%, p=0.006) of patients taking Stribild achieved HIV-1 RNA levels less than 20 copies/mL, a secondary endpoint. At week 144, virologic failure was similar between groups (Genvoya, 4.6%; Stribild, 3.9%); the difference in overall results was driven by fewer discontinuations on Genvoya due to adverse events or other reasons not related to efficacy (Genvoya, 11.2%; Stribild, 16%). There were statistically significant fewer adverse events leading to discontinuation in the Genvoya arm compared to the Stribild arm (Genvoya, 1.3%; Stribild, 3.3%, p=0.01). The most common drug-related adverse events in both groups were nausea, diarrhea and headache.
February 21, 2017
Theratechnologies released results of a phase III trial of ibalizumab for treatment-experienced patients infected with multidrug resistant HIV-1. TMB-301 was a single arm, 24-week study of ibalizumab plus optimized background regimen (OBR). Patients receiving their current failing antiretroviral therapy (ART), or no therapy, were monitored during a seven-day control period. Thereafter, a single loading dose of 2,000mg of intravenous (IV) ibalizumab was the only ART added to their regimen. The primary efficacy endpoint was the proportion of patients achieving a 0.5 log10 decrease in HIV-1 RNA seven days after initiating ibalizumab therapy, day 14 of the study. Ibalizumab was continued at doses of 800mg IV every two weeks through 24 weeks on study treatment. A total of 40 patients have been enrolled in the study. The new data showed that patients with multidrug resistant (MDR) HIV-1 infection experienced a mean increase in CD4+ T cell of 48 cells/μL after 24 weeks of treatment with ibalizumab plus an optimized background regimen (OBR). These data supplement previously reported findings, where 83% of patients achieved a 0.5 log10 decrease in viral load from baseline seven days after the single loading dose of 2000 mg of ibalizumab (primary endpoint) and a mean reduction in viral load of 1.6 log10 over the 24 week treatment period with more than 48% of patients experiencing a viral load reduction of more than 2.0 log10. A BLA to the FDA has been submitted.
August 1, 2016
ViiV Healthcare issued results of a phase IIIb, open-label, international, multicenter study of Triumeq (dolutegravir/abacavir/lamivudine) compared with atazanavir boosted with ritonavir (ATV/r) plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in 495 treatment-naïve women living with HIV. Results show statistically superior viral suppression (HIV-1 RNA <50 c/mL) rates at week 48: 82% versus 71% (adjusted difference 10.5%, 95% CI: 3.1%-17.8%, p=0.005) respectively. ARIA was a non-inferiority study with a pre-specified analysis for superiority. Both non-inferiority and superiority endpoints were met, with superiority being driven by lower rates of both virological failures and discontinuations due to adverse events (AEs) in the Triumeq group. The safety profile of Triumeq was favorable compared to ATV/r plus TDF/FTC, with fewer drug-related AEs reported on the Triumeq arm (33% v. 49%); there were also fewer AEs leading to discontinuation compared to those in the ATV/r plus TDF/FTC arm (4% vs 7%). Drug-related AEs reported in the Triumeq arm included nausea (31 individuals/13%), diarrhoea (12/5%), headache (5/2%) and dyspepsia (4/2%). In the ATV/r plus TDF/FTC group, drug-related AEs included nausea (35/14%), diarrhoea (18/7%), ocular icterus (18/7%), dyspepsia (15/6%), headache (14/6%) and jaundice (13/5%).
March 7, 2016
ViiV Healthcare reported results of a phase IIb, open label study of cabotegravir and rilpivirine (Janssen Sciences Ireland UC) as a two-drug treatment for patients with HIV-1 infection who had already achieved HIV viral suppression with a three drug oral regimen of cabotegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ongoing, international, multicenter, parallel group study included 309 HIV-infected adults who had not received prior anti-retroviral treatment. Enrolled patients were suppressed virologically (HIV-1 RNA <50
c/mL) during a 20-week induction period with daily oral cabotegravir (30mg) + 2 NRTIs and subsequently randomized to one of three study arms in the maintenance period: intramuscular cabotegravir long acting formulation (400mg) + rilpivirine long acting formulation (600mg) every four weeks; intramuscular cabotegravir long acting formulation (600mg) + rilpivirine long acting formulation (900mg) every eight weeks; or oral cabotegravir (30mg) + 2 NRTIs. The primary endpoint evaluated antiviral activity and safety through 32 weeks of maintenance treatment and the study will continue up to 104 weeks of treatment. Following 32 weeks of maintenance treatment, viral suppression rates for the two drug regimen dosed every eight weeks (95%) or every four weeks (94%) were comparable to the rate observed in patients continuing with a three drug oral regimen (91%). One patient in the eight week dosing group and one patient in the oral regimen group met protocol-defined virologic failure criteria; neither patient had evidence of resistance at failure. The most common drug-related adverse event reported by patients receiving injectable study medication was injection site pain (92%), of which most cases were mild (82%) or moderate (17%) in severity. The company plans a phase III study in late 2016.
August 24, 2015
CytoDyn has issued results of a phase IIb trial
of PRO 140 for HIV. PRO 140 reduces viral loads
by as much as 1.8log with one dose per week. In
the monotherapy study, some HIV patients are
experiencing suppressed viral load for 11 months.
The first self-injectable antibody, PRO 140, has
documented a 98% success rate. The company
has a phase III trial planned for 300 patients,
expected to begin by the end of Q3 2015. The
company may apply for a Breakthrough designation
with the FDA and plans to submit its NDA
for final approval of PRO 140 in November 2016.
PRO 140’s previous Fast Track designation carries
a possibility of accelerated approval.
March 16, 2015
Gilead Sciences issued results of two
phase III studies of tenofovir
alafenamide (TAF) for the treatment of HIV-
1 infection in treatment-naïve adults. Studies
104 and 111, extended to 144 weeks, were
randomized, double-blind, controlled trials
conducted among 1,733 treatment-naïve
adults living with HIV. A regimen of elvitegravir
150mg, cobicistat 150mg, emtricitabine
200mg and TAF 10mg (E/C/F/TAF) was found
to be statistically non-inferior to Gilead’s
Stribild (containing elvitegravir 150mg,
cobicistat 150mg, emtricitabine 200mg and
tenofovir disoproxil fumarate 300mg), based
on percentages of patients with HIV-1 RNA
levels less than 50 copies/mL. Patients were
randomized 1:1 to receive a single tablet
regimen of E/C/F/TAF or Stribild. At 48 weeks,
92.4% (n=800/866) of patients taking E/C/F/
TAF and 90.4% (n=784/867; CI -0.7% to
+4.7%, p=0.13) of patients taking Stribild
achieved HIV RNA levels less than 50 copies/
mL. Discontinuations due to adverse events
were low in both treatment arms (0.9% (n=8)
for E/C/F/TAF v. 1.5% (n=13) for Stribild), with
the most common side effects being diarrhea,
nausea, headache and upper respiratory
tract infection. Gilead filed an NDA for
E/C/F/TAF with the FDA on Nov. 5, 2014.
March 2, 2015
Sangamo BioSciences issued results of a
phase I/II trial of SB-728-T for HIV/AIDS. HIV-infected
subjects were enrolled in six cohorts. The
study evaluated the effect of increasing doses of
Cytoxan preconditioning as a method to maximize
engraftment of ZFN- modified cells (SB-
728-T). Cohorts 1-5 (18 subjects) were designed
primarily to evaluate the safety and tolerability of
escalating doses of cyclophosphamide (Cytoxan)
(doses tested: 200mg, 500mg/m, 1g/m, 1.5g/m
or 2g/m) administered prior to an infusion of
SB-728-T (CD4 cell enriched). The sixth cohort, Cohort
3 (three subjects) was designed to evaluate
a CD4/CD8 SB-728-T product post-administration
of Cytoxan at the optimal dose of 1g/m. Cytoxan
preconditioning at doses up to 1gm/m safely enhanced
total CD4 and CCR5 modified CD4 T-cells
(Cohorts 1-5). Data from Cohorts 1-5 demonstrated
a dose-related increase in both total CD4 T-cell
and ZFN modified CD4 T-cell engraftment in
response to Cytoxan preconditioning up to 1g/m.
In addition, all subjects underwent a treatment
interruption (TI) and were taken off antiretroviral
drugs (ART) at 16 weeks post infusion. Four subjects
from Cohort 1-5 remain on long-term TI and
have remained off ART for at least 40 weeks.
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.
November 10, 2014
Merck issued results of a phase IIb study
of doravirine, plus tenofovir/emtricitabine
(TDF/FTC) compared to efavirenz plus TDF/
FTC in previously untreated patients with
HIV-1 infection. The phase IIb randomized,
double-blind, dose-ranging clinical trial
enrolled 166 patients to receive once-daily
doravirine (25mg, 50mg, 100mg and 200mg)
compared to once-daily efavirenz 600mg,
both in combination with TDF/FTC. The
primary safety analysis from the expansion
phase of the study compared the incidence
of central nervous system (CNS) adverse
events (AEs) by week eight in patients who
received doravirine 100mg plus TDF/FTC
(n=108) v. patients who received efavirenz
with TDF/FTC (n=108). Additional follow-up
data through 48 weeks of treatment showed
a 76% (n=126/166) overall virologic response
rate (HIV RNA <40c/ml) for all doravirine
doses (25mg, 50mg, 100mg and 200mg) that
is comparable to 71% (n=30/42) reported
for patients administered efavirenz (600mg).
In addition, all treatment groups showed
increased CD4 cell counts relative to baseline,
consistent with the 24-week findings.
After 48 weeks of treatment, patients in the
dose-ranging part of the study who received
doravirine demonstrated a lower overall incidence
of drug-related adverse events (36.7%;
n=166) than those who received efavirenz
(57.1%; n=42). The company plans to initiate
phase III studies by the end of 2014.
October 6, 2014
Gilead Sciences issued results of two phase
III trials of tenofovir alafenamide (TAF) for
the treatment of HIV-1 infection in treatment-naïve
adults. Study 104 and Study 111 were
randomized, double-blind, 96-week clinical
trials among 1,744 treatment-naïve HIV-1
infected adults with viral load greater than or
equal to 1,000copies/mL. In Study 104, 867
patients were randomized (1:1) and received
E/C/F/TAF (n=435) or Stribild (n=432). In Study
111, 866 patients were randomized (1:1) and
received E/C/F/TAF (n=431) or Stribild (n=435).
The studies demonstrated the single tablet
regimen comprising elvitegravir 150mg, cobicistat
150mg, emtricitabine 200mg and TAF
10mg (E/C/F/TAF), was non-inferior to Gilead’s
Stribild (elvitegravir 150mg/cobicistat 150mg/
emtricitabine 200mg/tenofovir disoproxil
fumarate 30 mg) based on the proportion
of patients with HIV RNA levels (viral load) of
less than 50copies/mL at 48 weeks of therapy.
In addition, E/C/F/TAF demonstrated more
favorable renal and bone safety compared
to Stribild. There was a statistically significant
difference in the median change in estimated
glomerular filtration rate (eGFR) from baseline
to week 48, favoring the TAF-based regimen
(-6.8 mL/min for E/C/F/TAF v. -10.4mL/min for
Stribild in Study 104 (p<0.001); -5.7mL/min for
E/C/F/TAF v. -11.9mL/min for Stribild in Study
111 (p<0.001)). Additionally, patients taking
the TAF-based regimen experienced a significantly
smaller median percentage decrease
from baseline in lumbar spine bone mineral
density compared to Stribild patients (-1.19 v.
-2.67 in Study 104 (p<0.001); -1.11 v. -2.81 in
Study 111 (p<0.001)) and in hip bone mineral
density (-0.77 v. -3.24 in Study 104 (p<0.001);
-0.74 v. -2.78 in Study 111 (p<0.001)).
September 22, 2014
Sangamo BioSciences released results
of a phase I trial of SB-728-T for HIV/AIDS.
The study was an open-label trial to evaluate
single infusions of an escalating dose of
an autologous (a patient’s own) CD4+ T-cell
product genetically modified at the CCR5
gene by CCR5-specific ZFNs (SB-728-T). The
trial enrolled nine HIV-infected subjects
(three cohorts of three subjects each) who
had sub-optimal T-cell levels and no detectable
viral load on long-term ART, so-called
immunologic non-responders (INRs). Three
CCR5 delta 32 heterozygote subjects have
controlled VL to undetectable or <1000 copies
during a treatment interruption (TI) from
ART, one for more than 59 weeks (to last measurement
taken). Two subjects experienced
a two-log decrease in viral load from peak
(with Cytoxan conditioning of 1gm/m and
1.5gm/m), which has been sustained in one
subject for more than 39 weeks. Five subjects
currently remain on extended TI (longer than
the 16 week period defined in the protocol)
with VLs <10,000 copies and CD4 counts of
>500. Analyses showed a large increase in
CCR5-modified cells in the long-lived T(SCM)
compartment, which may explain why CCR5-
modified cells from a single infusion can be
detected in all subjects over a prolonged period
(more than 42 months). A median 0.9 log
decrease in the size of the HIV reservoir at 36
months was observed in nine of nine subjects
treated, as demonstrated by measurement
of HIV total DNA in PBMCs. The decrease in
reservoir showed a statistically significant correlation
with an improvement in CD4 count.
Sangamo is conducting an ongoing phase II
clinical trial, SB-728-mR-1401 (1401).
August 4, 2014
The San Francisco AIDS Foundation
reported results of additional, long-term data
of PrEP for HIV. The 72-week, open-label extension
of iPrEx enrolled 1,603 HIV uninfected persons
with an average age of 28 at 11 sites on
four continents. All participants had previously
taken part in randomized, blinded, placebo-controlled
trials of oral PrEP. 76% of OLE
participants chose to receive once-daily oral
PrEP with emtricitabine/tenofovir disoproxil
fumarate (FTC/TDF), while the remainder chose
to participate in the study without receiving
PrEP. No study participant who took PrEP four
or more times per week became HIV-infected.
The study measured participant use of PrEP
in dried blood spots (DBS), a novel and highly
sensitive biomarker of long-term PrEP. Among
those receiving PrEP in the study iPrEx OLE,
HIV incidence was 4.7/100PY if drug was not
detected in DBS, 2.3/100PY if drug concentrations
indicated use of fewer than two tablets
per week, 0.6/100PY for use of two to three
tablets per week and 0/100PY for use of four or
more tablets per week (P<0.0001).
October 28, 2013
Tobira Therapeutics released results from a phase IIb trial of cenicriviroc (CVC) for the treatment of HIV infection. The randomized, placebo-controlled, double-blind, double-dummy, dose-finding, 48-week study enrolled 143 HIV treatment-naïve adults with CCR5-tropic HIV infection (patients with CCR5- tropic virus represent approximately 80% of the treatment-naïve HIV-infected population). At week 48, CVC 100mg or CVC 200mg plus Truvada (emtricitabine/tenofovir disoproxil fumarate) showed similar virologic success rates compared to Sustiva (efavirenz or EFV) plus Truvada (68% and 64% v. 50%, FDA Snapshot Analysis-ITT). CVC was associated with a more favorable safety and tolerability profile compared to EFV, including a lower incidence of Grade 3 or higher adverse events (AEs) (4% for all CVC-treated subjects v. 14% for EFV) and discontinuations due to AEs (1% for all CVC-treated subjects v. 21% for EFV) reported. The FDA supports initiation of phase III studies to evaluate CVC as a component of a nucleos(t)ide-sparing “backbone” of cenicriviroc/lamivudine (CVC/3TC).
October 7, 2013
ViiV Healthcare released results of a phase IIIb/IV study comparing once-daily regimens containing 50mg dolutegravir with once-daily regimens containing a protease inhibitor (PI) (800mg darunavir boosted with 100mg ritonavir) in treatment-naïve adults with HIV-1. The trial was a 96-week, ongoing, randomized, multi-center, multinational, open-label, non-inferiority (-12% margin) study. At 48 weeks, a significantly greater proportion of the patients treated with the dolutegravir regimen (90%) were virologically suppressed (HIV-1 RNA <50 copies/mL, the primary endpoint of the study per FDA snapshot) compared to those treated with the darunavir regimen (83%, adjusted treatment difference [95% CI] 7.1% (0.9%, 13.2%); P=0.025; N=242 in each arm). Comparing the dolutegravir and darunavir arms, rates of virologic non-response were 6% v. 7%, rates of treatment withdrawal due to adverse events were 1% v. 4% and rates of treatment withdrawal for other reasons were 2% v. 5%. This study and three others formed the basis of the registration package leading to FDA approval of Tivicay in August.
July 29, 2013
Inovio Pharmaceuticals has released results from two phase I trials (HVTN 070 and HVTN 080) of Pennvax-B preventative HIV DNA vaccine, HVTN 070 without electroporation and HVTN 080 with electroporation. Both trials were multicenter, randomized clinical trials, with 070 enrolling 120 patients and 080 enrolling 48 patients. Robust T-cell responses were generated in 89% of subjects who received three vaccinations of Pennvax-B, which consists of 1mg of each of three DNA plasmids (encoding for HIV gag, pol and env proteins) along with 1mg of IL-12 DNA plasmid, followed by intramuscular electroporation with Inovio’s CELLECTRA device. Three or four vaccinations with a 2mg dose of each Pennvax-B plasmid plus 1.5mg of IL-12 DNA generated fewer responses when delivered without electroporation. Six months after vaccination, T-cell response rates remained strong and persistent in the subjects who received only three doses delivered by CELLECTRA EP. Of 24 positive CD4 or CD8 Tcell responders following the third in month three, 79% (19/24) showed persistent CD4 or CD8 T-cell responses at month nine.
June 17, 2013
Immune Response BioPharma reported results from a phase II trial of IR103 REMUNEX for the treatment of HIV. This randomized, single-blind, controlled, comparative study was conducted over 52 weeks at three clinical sites; one in Canada and two in the U.K. A total of 180 participants were randomized into four treatment groups. Groups one and four had a combined total of 80 individuals who received HAART-inclusive of NNTRI, a class of antiretroviral drug that inhibits the action of reverse transcriptase, and had an undetectable viral load. Groups two and three were each comprised of 50 individuals who had no more than seven days of antiretroviral treatment at any time prior to study entry (antiretroviral-naïve), with a viral load between 1,000 and 60,000 copies/ml. The combination of Remune with Amplivax was well tolerated with no serious adverse events reported. The study results support further evaluation of this combination as a therapeutic HIV vaccine.
March 18, 2013
Kowa Pharmaceuticals America and Eli Lilly issued results from a phase IV trial of Livalo compared to pravastatin for reducing low-density lipoprotein cholesterol (LDL-C). This randomized, double-blind, double-dummy, active-controlled, parallel-group superiority study enrolled 252 HIV-infected patients with high cholesterol and with or without viral hepatitis B or C. Subjects received Livalo 4mg or pravastatin 40mg once daily. Results showed after 12 weeks of therapy, Livalo had a significantly greater decrease in LDL-C compared with pravastatin (Livalo -49.4mg/dL and pravastatin -33.6mg/dL, 31% versus 21% reduction, respectively, p<0.001). Livalo was well tolerated. The most frequent treatment emergent adverse events were diarrhea, upper respiratory tract infection, sinusitis, headache, nausea, nasopharyngitis and increase in blood creatine phosphokinase. Eleven subjects were discontinued from the study due to a TEAE.
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.
December 10, 2012
Profectus BioSciences issued results from a phase I trial of its recombinant vesicular stomatitis virus (rVSV)-vectored HIV vaccine. This placebo-controlled, dose-escalation study enrolled 60 patients without HIV. Subjects received 104, 105, 106, 107 and 108 plaque-forming units of the rVSV HIV-1 gag vaccine administered by intramuscular injection. The vaccine was found to be safe at all dose levels, and the 108 PFU dose has been selected for evaluation in a follow-on clinical trial (HVTN 087). Assays conducted by Profectus confirmed that 0% of subjects had pre-existing immunity to VSV, that there was a vaccine “take” in 50/50 (100%) vaccine recipients across all dose levels and that no rVSV entered the blood stream or was shed in saliva or urine. Assays conducted by the HVTN Central Immunology Laboratories demonstrated the 108 PFU dose level induced a gag-specific cell-mediated immune (CMI) response in 62.5% of vaccine recipients. Profectus is waiting for results from its pDNA prime/rVSV boost vaccination strategy before advancing the vaccine to phase II.
November 28, 2012
Gilead Sciences released results from a phase III trial of Stribild (elvitegravir 150mg, cobicistat 150mg, emtricitabine 200mg, tenofovir disoproxil fumarate 300mg) for the treatment of HIV. This randomized, double-blind study, Study 102, enrolled treatment-naïve patients with HIV-1 infection with HIV RNA levels greater than or equal to 5,000 copies/mL. Subjects received either Stribild or Atripla (efavirenz 600mg, emtricitabine 200mg, tenofovir disoproxil fumarate 300mg). Data show Stribild was non-inferior to Atripla after two years of treatment. Results found at 96 weeks of treatment, 84% of Stribild patients (n=293/348) and 82% of Atripla patients (n=287/352) achieved HIV RNA (viral load) <50 copies/mL, based on the FDA snapshot algorithm (95% CI for the difference: -2.9% to +8.3% for Stribild versus Atripla; predefined criterion for non-inferiority was a lower bound of a two sided 95% CI of -12%). The most frequent adverse events were diarrhea, nausea, upper respiratory infection, headache, abnormal dreams, fatigue, depression and insomnia. Based on these data, Gilead Sciences has initiated a phase IIIb study evaluating Stribild compared to ritonavir-boosted atazanavir plus Truvada in more than 500 HIV-positive treatment-naïve females.
November 5, 2012
Gilead Sciences reported interim results from a phase II trial of tenofovir alafenamide fumarate (TAF) for the treatment of HIV-1 infection. This randomized, double-blind, 48-week study enrolled 170 patients with HIV RNA levels ≥5,000 copies/mL and CD4 cell counts ≥50 cells/mm3. Subjects were divided into two arms. The first arm received a once-daily tablet containing TAF 10mg, elvitegravir 150mg, cobicistat 150mg and emtricitabine 200 mg. The second arm received Stribild. Bone mineral density was assessed in all patients by DEXA scans at baseline and at week 24. Compared to Stribild, the TAF-based regimen demonstrated statistically significantly smaller reductions from baseline to week 24 in bone mineral density at the lumbar spine and hip (p<0.005). In addition, small, statistically significant differences were seen in serum creatinine and in calculated creatinine clearance between the two arms in favor of the TAF-containing regimen (p<0.02). The drug was well tolerated. Both arms demonstrated similar adverse events. Gilead plans to submit these data for presentation at a scientific conference next year. The company is also studying TAF in a second phase II trial.
July 30, 2012
Gilead Sciences released results from a phase III trial of cobicistat compared to ritonavir for the pharmacoenhancing or “boosting” of HIV therapy. This randomized, double-blind study, Study 114, enrolled 357 HIV-infected treatment-naïve patients. Subjects received a once-daily regimen of atazanavir 300mg and Truvada, plus either cobicistat 150mg or ritonavir 100mg for 192 weeks. Results found that the cobicistat regimen was non-inferior to the ritonavir regimen. At 48 weeks, the study found that 85% of the cobicistat-dosed subjects compared to 87% of the ritonavir-dosed subjects achieved HIV RNA (viral load) levels less than 50 copies/mL, based on the FDA snapshot algorithm. Mean increases in CD4 cell counts were 213 cells/mm3 for cobicistat patients and 219 cells/mm3 for ritonavir patients at 48 weeks (p=0.67). The drug was well tolerated. The most common adverse events were jaundice, ocular icterus, nausea, diarrhea, headache, nasopharyngitis, hyperbilirubinemia and upper respiratory infection. Gilead Sciences has submitted a New Drug Application to the FDA for cobicistat.
July 16, 2012
Shionogi-ViiV Healthcare reported interim results from a phase III trial of ING114467 versus Atripla for the treatment of HIV-1. This double-blind, double-dummy study, SINGLE, enrolled 833 patients. Subjects received dolutegravir 50mg plus abacavir/lamivudine or Atripla (tenofovir/emtricitabine/efavirenz) for 48 weeks. Results showed the dolutegravir-based regimen demonstrated superiority over the Atripla regimen. At 48 weeks, 88% of study participants on the dolutegravir regimen were virologically suppressed (<50 copies/mL) vs. 81% of participants on the single-tablet regimen Atripla (difference and 95% CI; 7.4% [+2.5% to +12.3%]; difference in the primary endpoint was statistically significant, p=0.003). Differences in efficacy were primarily driven by a higher rate of discontinuation (10%) due to adverse events on the Atripla arm (only 2% of subjects in the dolutegravir arm discontinued). The most common drug-related adverse events were in the nervous system System Organ (Atripla) and gastrointestinal system organ class (dolutegravir). Shionogi-ViiV Healthcare is expecting results from two other phase III trials of dolutegravir for the treatment of HIV.
March 19, 2012
Inovio Pharmaceuticals issued results from a phase I trial of PENNVAX-B, a vaccine for the treatment HIV subtype B, prevalent in North America and Europe. This open label trial, HIV-001, enrolled 12 adult HIV-positive subjects who received a four dose series (day 0, weeks 4, 8 and 16) of PENNVAX-B containing 3 mg of DNA/dose via intramuscular electroporation. All subjects completed the four dose vaccination regimen. Significant vaccine-specific T-cell responses against at least one of the three vaccine antigens (gag. pol, or env) were observed in 75% of subjects following vaccination. Fifty percent of the subjects had strong vaccine induced antigen-specific responses above the pre-vaccination levels to at least two of the antigens. The responses induced by vaccination were predominantly antigen-specific CD8+ T-cells. There were no significant adverse events or vaccine related grade 3 or 4 adverse events and the vaccine was generally well tolerated.
September 26, 2011
Gilead issued results from a phase III trial of their fixed-dose, single-tablet Quad regimen of elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil fumarate for HIV. This randomized, double-blind clinical trial (103) enrolled approximately 700 HIV-infected treatment-nave adults who received the Quad regimen or ritonavir-boosted atazanavir plus Truvada (emtricitabine/tenofovir). The primary endpoint was non-inferiority between the treatment groups, based on the proportion of subjects who achieved HIV RNA levels of less than 50 copies/mL at week 48. This endpoint was reached by 90% of the Quad arm compared to 87% of the comparator arm. The discontinuation rate due to adverse events was higher in the comparator arm (5.1%) as compared to the Quad arm (3.1%).
September 19, 2011
Inovio reported interim results from a phase I trial of PENNVAX-G, a global HIV vaccine. This randomized, open label trial, RV262, plans to enroll 92 healthy subjects in the U.S and Africa. This interim data are from the first cohort of 11 subjects who received a priming immunization with PENNVAX-G at months zero and one, followed by boosting with MVA-CMDR at months three and six. Data revealed a strong cell-mediated immune response, with CD4+ and CD8+ T cells specific for both the gag and env antigens encoded by the prime and boost agents. Anti-env CD4+ T-cell immune responses were noted in 100% (11 of 11) of evaluated subjects and CD8+ T-cell responses were noted in 45% of evaluated subjects after the first MVA boost following the two DNA vaccinations. The env specific CD4+ and CD8+ T-cell response rates were noted to be 73% and 45% respectively after the second MVA boost.
July 25, 2011
SEEK Biopharmaceuticals issued results from a phase Ib/II trial of HIV-v, their investigational prophylactic and therapeutic HIV vaccine. The trial enrolled 55 HIV-positive subjects who were placed in five groups: four vaccinated with the HIV-v vaccine and one placebo. The four vaccinated groups were divided into low-dose with and without adjuvant and a higher-dose with and without adjuvant. After a single injection there was a 90% reduction in the viral load of vaccinated subjects compared with placebo subjects.
March 28, 2011
Gilead Sciences issued results from a phase III trial of elvitegravir for the treatment of HIV. This randomized, double-blind, 48-week trial enrolled 702 HIV-infected, treatment-experienced subjects. The subjects continued their background regimen plus received either elvitegravir 150 mg once-daily or raltegravir (Isentress; standard of care) 400 mg twice-daily. The primary endpoint was non-inferiority, measured by the proportion of subjects in both arms who achieved and maintained confirmed viral load of less than 50 copies/mL through 48 weeks. The primary endpoint was reached. Analysis indicated that 59% of subjects in the elvitegravir arm and 57.8% in the raltegravir arm achieved and maintained the endpoint goal. Adverse events were similar between the treatment arms. Based on the achievement of the primary endpoint, the trial was extended out to 96 weeks to long term safety and efficacy data.
March 7, 2011
Sangamo issued preliminary results from a phase I trial of evaluating their CCR5-modified, autologous T-cell product, SB-728-T, for the treatment of HIV. This open label trial, SB-728-T-902, enrolled 13 HIV infected subjects on long-term, stable anti-retroviral therapy whose virus was undetectable in their blood by conventional methods but who exhibited suboptimal CD4+ T-cell gains. The subjects were placed in three sequential dosing cohorts: a single dose, two doses at 14 day intervals or three doses at 14 day intervals. The data demonstrated that a single infusion of SB-728-T was well tolerated; the CCR5-modified cells were successfully engrafted in all subjects and resulted in a durable improvement in total CD4+ T-cell counts in five of six of the subjects analyzed. Five of the six subjects also exhibited sustained improvements in their CD4:CD8 T-cell ratio. The ZFN-CCR5-modified cells also exhibited normal T-cell growth kinetics and trafficking and were observed to undergo selective expansion in the gut mucosa, a reservoir of virus in the body, suggesting that the cells were resistant to HIV infection.
Vertex and Tibotec reported interim results from a phase II trial evaluating telaprevir for hepatitis C and HIV co-infection. This two-part (A and B), randomized, double-blind, placebo-controlled, parallel group trial enrolled 60 subjects infected with both genotype 1 hepatitis C virus and human immunodeficiency virus. The subjects received either 12 weeks of telaprevir or placebo in combination with peginterferon alfa-2a and ribavirin, followed by 36 weeks of peginterferon alfa-2a and ribavirin alone. Part A (n≡13) of the study enrolled subjects who were not receiving antiretroviral therapy for the treatment of HIV. Part B (n≡47) enrolled subjects who were being treated for HIV with either Atripla (n≡24) or a Reyataz-based regimen (n≡23). Preliminary data form both arms (n≡59) showed that 70% of the subjects receiving the telaprevir-based combination therapy had undetectable hepatitis C virus by week four (rapid viral response) compared to 5% of the subjects receiving pegylated-interferon and ribavirin alone. A complete early viral response was seen among 68% of the telaprevir-based group versus 14% of the control group at week 12. The majority of adverse events were mild to moderate
November 22, 2010
Inovio Pharmaceuticals reported positive preliminary results from a phase I trial of PENNVAX-B, a DNA vaccine for the prevention of HIV clade B. This randomized, double blind, placebo controlled trial (HVTN 080) enrolled 48 healthy, uninfected subjects in the US. The subjects received a placebo, a 1 mg dose of PENNVAX-B vaccine, or a 1 mg dose of PENNVAX-B along with IL-12 DNA. The vaccine or placebo was administered with electroporation at months 0, 1, and 3. Preliminary data include safety data from all subjects and immunogenicity data from 38 out of 40 samples from vaccine recipients post-second-dose and from 31 out of 40 samples from vaccine recipients post-third-dose. After two vaccinations, 61% of evaluated subjects receiving PENNVAX-B showed either CD4+ or CD8+ or both T-cell responses against at least one of the vaccine antigens. After three vaccinations, 84% of evaluated subjects had positive T-cell responses. In addition, 67% (6 of 9) of evaluated subjects receiving PENNVAX-B and 91% (20 of 22) of evaluated subjects receiving PENNVAX-B + IL-12 were observed to have generated antigen-specific T-cell responses (either CD4+ or CD8+). Antigen-specific CD4+ T-cell responses were generated by the vaccine in 70% of evaluated subjects (21 out of 30) and strong antigen-specific, CD8+ T-cell responses were also generated by the vaccine in 55% of evaluated vaccine recipients (17 out of 31). The vaccine with or without IL-12 was generally safe and well tolerated.
August 2, 2010
Tibotec reported positive pooled results from two phase III trials of TMC278 for the treatment of HIV. These double-blind, randomized studies, ECHO and THRIVE, enrolled 1,368 treatment-naive, HIV-1-infected adults. ECHO evaluated TMC278 (25 mg) once daily, versus efavirenz (EFV) (600 mg) once daily, combined with a fixed background regimen consisting of emtricitabine + tenofovir disoproxil fumarate. THRIVE evaluated TMC278 (25 mg) once daily versus EFV (600 mg) once daily, combined with an investigator-selected background regimen consisting of two N[t]RTIs (abacavir + lamivudine or emtricitabine + tenofovir disoproxil fumarate or zidovudine + lamivudine). Both trials reached their primary objective, the non-inferiority of TMC278 versus EFV in the proportion of patients achieving an undetectable viral load (less than 50 copies/mL) at week 48. Results showed that 84.3% of subjects in the TMC278 group reached an undetectable viral load, compared with 82.3% of patients in the EFV group. The virologic failure rate was 9% in the TMC278 group and 4.8% in the EFV group.
July 26, 2010
FIT Biotech released positive results from a phase II trial of FIT-06, a DNA-based therapeutic vaccine for HIV. This placebo controlled trial enrolled 60 previously untreated subjects in South Africa. The subjects were dosed either intramuscularly or intradermally. FIT-06 showed long-term reductions in viral load (approximately 0.5 log) and statistically significant CD4 cell count increases which lasted longer than two years in the absence of any anti-retroviral therapy. After 108 weeks, viral loads were reduced by 0.47 log (p≡0.001) in the intramuscular group. CD4 cell counts increased by 72 cells per l (p≡0.013).
Tobira Therapeutics issued positive results from a phase IIa trial of TBR-652 for the treatment of HIV. This double-blind, placebo-controlled, dose-escalation trial (652-2-201) enrolled 54 subjects treatment-experienced. The subjects were randomized to receive TBR-652 in doses of 25mg, 50mg, 75mg, 100mg, 150mg or placebo once daily for ten days. TBR-652 monotherapy produced a median nadir decline from baseline in HIV viral load of up to 1.8 log10 copies/mL. There were no serious adverse events, deaths or study drug-related discontinuations. In addition, dose-dependent changes in concentrations of monocyte chemoattractant protein-1 (MCP-1) were observed, providing evidence of TBR-652's dual action on CCR5 and CCR2, and showing the potential anti-inflammatory benefit of the compound.
Results were reported from a phase IIb trial evaluating Gileads tenofovir gel as a microbicide against HIV and genital herpes. This trial, CAPRISA 004 (Centre for the AIDS Programme of Research in South Africa), enrolled 889 South African women who were 18 to 40 years of age, HIV-negative, sexually active, and at high risk of becoming infected with HIV. The subjects were asked to vaginally insert a first dose of tenofovir gel no more than 12 hours before having sex and to insert a second dose no more than 12 hours after having sex. No more than two doses of gel were used in a 24-hour period. The treatment period was 12 to 18 months. The gel was found to be 39% effective in reducing the risk of becoming infected with HIV during sex and 51% effective in preventing genital herpes infections. The efficacy of tenofovir was greater with increased usage. The women who used the gel more than 80% of the time had a 54% reduction in HIV infections, whereas those who used the gel less than half the time had a 28% reduction in HIV infections.
March 23, 2009
Avexa released positive long-term results from an ongoing phase IIb extension study of apricitabine (ATC) for the treatment of HIV. This is an extension of AVX-201, a 48-week study which was conducted in three segments. For the first 21 days, subjects received 600 mg or 800 mg ATC twice daily or continued on lamivudine without changing their background drug regimen. At day 21, subjects continued on ATC or lamivudine as before, but their background drugs were optimized. At week 24, all subjects were offered open label ATC 800 mg twice daily. Reported data is from 96-weeks of continuous treatment. At week 96, the number of subjects with plasma levels of HIV below the limit of detection (<400 copies/mL) was 87%. Levels of CD4 cells continued to increase; at week 96 the average number of CD4 cells was around 500 to 600 cells/L. No resistance to ATC has been identified. ATC continues to be well tolerated and most adverse events are mild or moderate in nature.
February 16, 2009
Indevus reported positive results from a phase II/IIb trial of PRO2000 for the prevention of HIV. This randomized, placebo-controlled, double blind study, dubbed HPTN 035, enrolled approximately 3,100 HIV-uninfected women across sites in Zimbabwe, Malawi, Zambia, South Africa, and the USA. The four-arm trial compared PRO2000, BufferGel (ReProtect), a placebo gel, and no gel. Women enrolled in the three gel arms were to apply the product vaginally up to one hour before each act of sexual intercourse. They were subsequently followed for 12-30 months. The primary endpoint was efficacy in preventing of HIV transmission. Additional endpoints included the prevention of bacterial vaginosis, herpes virus infection, and other sexually transmitted diseases. Of the 3,100 enrolled subjects, 194 new HIV infections occurred over the course of the trial. Of these, 36 occurred in the PRO 2000 arm, 54 in the BufferGel arm, 51 in the placebo arm, and 53 in the no-gel arm, demonstrating that PRO2000 was at least 30% more effective than any other arm in preventing HIV. PRO2000 did not show protection against any other sexually transmitted infection. The treatment was well tolerated.
Progenics issued positive results from a phase II trial of subcutaneous PRO 140 for the treatment of HIV. This multi-center, randomized, double-blind, placebo-controlled trial enrolled 44 treatment-naive subjects, or those not on therapy for at least three months. The subjects received three weekly doses of 162 mg of PRO 140, two bi-weekly doses of 324 mg of PRO 140, three weekly doses of 324 mg of PRO 140, or placebo, and were followed for a total of 58 days. The mean maximum reduction in viral load was 0.99 log10, 1.37 log10 and 1.65 log10 for the three groups, respectively, and the mean reduction in viral load was 0.75 log10, 1.20 log10 and 1.51 log10 for the three groups, respectively. The drug was well tolerated with no drug-related serious side effects.
August 11, 2008
Merck reported positive results from an ongoing phase II trial of Isentress for the treatment of HIV. This multi-center, dose-ranging, double-blind, randomized trial enrolled 198 treatment-nave HIV-infected subjects. The subjects received Isentress administered orally twice daily in combination with tenofovir and lamivudine or 600 mg efavirenz (dosed orally once daily in combination with the same agents. During the first 48 weeks of the study, four dose regimens of Isentress (100, 200, 400 and 600 mg) were studied. After 48 weeks, all Isentress groups received 400 mg dosed twice daily. The primary endpoints were reductions in HIV RNA less than 400 copies/mL and the evaluation of safety at 96 weeks. At baseline mean HIV RNA for subjects on the Isentress combined regimen was approximately 55,000 copies/mL and for the efavirenz regimen was approximately 68,000 copies/mL. Mean baseline CD4 cell counts were 305 and 280 cells/mm for the groups receiving Isentress and efavirenz, respectively. Following 96 weeks of treatment the Isentress combination therapy reduced HIV viral load to undetectable levels, with 83% of subjects achieving reductions in HIV RNA levels below 50 copies/mL. These results were comparable for subjects in the efavirenz treatment arm, with 84% of subjects achieving reductions in HIV RNA levels below 50 copies/mL. Similarly, 84% of subjects in both treatment arms maintained reductions in HIV RNA levels to below 400 copies/mL. In addition, subjects on both treatment regimens experienced increases in CD4 cell counts at 96 weeks. The mean increase from baseline in CD4 cell count was 221 cells/mm3 for subjects taking Isentress and 232 cells/mm for those taking efavirenz. Treatment was generally safe and well tolerated. Based on the results, Merck plans to move forward with the development of Isentress for this treatment nave population.
June 30, 2008
Ardea issued positive results from a phase IIa trial of RDEA806 for the treatment of HIV. This randomized, double-blind, placebo-controlled trial enrolled 48 HIV-positive subjects who were naive to antiretroviral treatment. The subjects received either an enteric-coated tablet formulation of RDEA806 (800 mg or 1000 mg once daily), a capsule formulation (400 mg twice daily or 600 mg once daily) or placebo. The primary efficacy end point was the change from baseline in plasma viral load. The median reduction in plasma viral load at nadir was 1.9 - 2.1 log copies/ml (placebo adjusted) for all four treatment cohorts. Subjects receiving either the 800 mg or 1000 mg once daily enteric-coated tablet formulation, and those receiving the 400 mg twice daily capsule formulation, experienced a 1.8 - 1.9 log median reduction in plasma viral load (adjusted for placebo) on Day 8. The 600 mg capsule formulation given once daily produced a 1.4 log median reduction (adjusted for placebo) at this time point. Treatment was well tolerated with no serious adverse events reported. Based on the results, Ardea plans to initiate a phase IIb trial in Q3 of 2008.
June 23, 2008
Idenix released positive results from a phase I/II trial of IDX899 for the treatment of HIV-1. This study enrolled 30 treatment nave subjects who were randomized in three cohorts 8:2 to receive 800 mg/day, 400 mg/day and 200 mg/day of IDX899 orally once-daily or placebo, for seven days. The subjects receiving daily oral administration of 800 mg, 400 mg and 200 mg IDX899 achieved mean viral load reductions of 1.78, 1.78, and 1.83 log(10), respectively, compared to a mean plasma viral load increase of 0.05 log(10) for placebo. The mean CD4+ count change from baseline increased by at least 60 cells/mm3 for each of the 800 mg, 400 mg and 200 mg dosing cohorts and decreased by about 80 cells/mm3 for patients receiving placebo. Treatment was well tolerated. Based on the antiviral activity of IDX899 seen to date, the study was amended to also evaluate a lower dose of 100 mg/day. Treatment at this dose is currently under evaluation.
Pharming Group issued positive results from a phase III trial of Rhucin for the treatment of Hereditary Angioedema (HAE). This randomized double-blind placebo-controlled study enrolled 39 subjects in North America. On having an acute HAE attack the subjects received one of two doses of Rhucin (100 U/kg, 50 U/kg) or placebo. The primary endpoint was time to beginning of symptom relief. In the subjects who received the 100 U/kg dose of Rhucin, the median first symptom relief was approximately 68 minutes, those that received the 50 U/kg dose reported relief at approximately 100 minutes, and those that received placebo reported symptom relief at approximately 258 minutes. The time to minimal clinical symptoms, the secondary endpoint, was reported by subjects in the 100 U/kg, 50 U/kg, placebo groups at approximately 245, 247, and 1098 minutes, respectively. The primary and secondary endpoint results with both doses of Rhucin were statistically significant relative to placebo (p-values < 0.01). Based on the results Pharming Group plans to meet with EMEA and FDA to accelerate regulatory filings in Europe and the USA.
March 17, 2008
Avexa reported positive results from a phase IIb trial of apricitabine (ATC) for the treatment of HIV. This forty-eight week trial enrolled fifty one subjects and was conducted in three segments. For the first twenty one days, subjects received 600 mg or 800 mg ATC twice daily, or continued on lamivudine (3TC), without changing their background drug regimen. At day twenty one, subjects continued on ATC or 3TC as before, but their background drugs were optimized. At week twenty four, all subjects were offered open label ATC 800 mg twice daily. The forty-eight week data was as follows: in the 800mg ATC dose arm more than 90% of subjects had plasma levels of HIV less than 400 copies/mL and more than 80% had less than 50 copies/mL. A similar response was seen in the subjects who initially received the 600mg dose of ATC and then crossed over to the 800mg dose for the second twenty four weeks. No evidence of resistance to ATC was observed up to week 48. The subjects who were initially treated with 3TC and then switched to ATC showed improvements in both their viral load and their CD4 cell count after switching to ATC. The levels of CD4 cells at week forty eight had nearly doubled compared to the levels after twenty four weeks of 3TC. In addition, subjects switching from 3TC to ATC obtained, on average, approximately a further 0.5 log decrease in their viral load. Treatment was well tolerated, with adverse events mild to moderate in nature. Phase III trials of apricitabine are currently underway.
March 10, 2008
NeurogesX issued negative preliminary results from a phase III trial of NGX-4010 for the treatment of HIV-distal sensory polyneuropathy (HIV-DSP). This multi-center, randomized, double-blind, controlled study, dubbed C119, enrolled 494 subjects in Australia, Canada, the UK and the US. The subjects received a single 30- or 60-minute treatment with NGX-4010 or low concentration control patch, applied directly to the site of pain. After 30 to 60 minutes, the patch was removed and the response levels were evaluated during a subsequent 12-week study period. The pre-specified primary endpoint, comparing all subjects treated with NGX-4010 to all subjects treated with the control patch, did not meet statistical significance. The 30-minute NGX-4010 treatment arm achieved a 26.1% reduction in pain from baseline compared to 19.1% for the control group (p=0.1). The 60-minute treatment arm achieved a 32.8% reduction in pain from baseline compared to 30.1% for the control group (p=0.5). Secondary endpoints also did not achieve statistical significance. NeurogesX plans to fully analyze the data in order to determine the best path towards regulatory approval.
February 18, 2008
Schering Plough reported positive long-term results from a phase II study of vicriviroc for the treatment of HIV. This randomized, placebo-controlled, double-blind study was dubbed VICTOR-E1 (Vicriviroc in Combination Treatment with Optimized Antiretroviral Therapy Regimen in Experienced Subjects). A total of one hundred and sixteen treatment-experienced adults with the R5-type virus were enrolled in Europe, South Africa and North and South America. The subjects received vicriviroc (30 mg or 20 mg once daily) in combination with a new optimized ritonavir-boosted, protease inhibitor-containing antiretroviral regimen or the new optimized background therapy alone. Data revealed potent and sustained viral suppression in the vicriviroc arms, with significantly greater decreases in mean HIV-RNA, as well as greater increases in mean CD4 counts, compared to the control arm. At forty eight weeks, subjects in the 30 mg and 20 mg vicriviroc treatment groups achieved mean decreases from baseline in viral load of -1.77 and -1.75 (log10 copies/mL), respectively, compared to -0.79 for the control group (p=0.0017 and p=0.0026, respectively). Mean increases from baseline in CD4 cell counts in the vicriviroc groups were +102 and +134 (cells/mm3), respectively, compared to +65 in the control group. Fewer subjects in the vicriviroc groups discontinued from the study due to virologic failure compared to those in the control group (13% and 8% versus 38%, respectively). Phase III trials of vicriviroc are currently underway.
February 11, 2008
Achillion released positive twenty-four week results from a phase II trial of elvucitabine for the treatment of HIV. This randomized, double-blind study enrolled seventy eight treatment-nave subjects with wild-type HIV-1 virus. The subjects received 10 mg/day elvucitabine with 600 mg/day efavirenz and 300 mg/day tenofovir or 300 mg/day 3TC with 600 mg/day efavirenz and 300 mg/day tenofovir. The study included a twelve-week blinded treatment period after which responders (subjects with viral loads below 400 copies/mL, or less than 2 log10 decrease) continued to an ongoing eighty four-week open-label extension period. Elvucitabine had a potent anti-viral effect similar to 3TC, with a mean change in HIV-RNA from base-line in the elvucitabine treatment group of -3.0 log10 (+/- 0.6) versus -3.2 log10 (+/- 0.5) in the 3TC treatment group. In the elvucitabine-treated group, 96% of subjects reached undetectable viral load, defined as achieving fewer than 50 copies/ml after twenty four weeks of therapy, compared to 94% in the 3TC-treated group. Elvucitabine was well-tolerated and demonstrated a safety profile comparable to 3TC for both incidence and severity adverse events. Analysis of forty-eight and ninety-six week data are currently under evaluation.
Amgen issued positive pooled results from two phase III trials of Nplate for the treatment of Idiopathic Thrombocytopenic Purpura (ITP). These parallel phase III trials enrolled sixty three splenectomized subjects and sixty two non-splenectomized subjects with ITP and a mean of three platelet counts of 30,000 per microliter or less. The subjects were randomized to subcutaneous injections of Nplate (n=42 in splenectomized study and n=41 in non-splenectomized study) or placebo (n=21 in both studies). The primary endpoint was efficacy as measured by a durable platelet response and treatment safety. Durable response was defined as a platelet count above 50,000 per microliter during six or more of the last eight weeks of treatment without rescue therapy ever being administered. The durable platelet response rate was significantly greater in subjects treated with Nplate compared to those in the placebo group in both studies (difference in proportion of splenectomized subjects responding 38% (95% CI (23.4-52.8 percent); p less than 0.0001); difference in proportion of non-splenectomized subjects responding 56% (95% CI (38.7-73.7 percent); p less than 0.0001)). The overall platelet response was 88% in non-splenectomized subjects compared to 14% in the placebo group; and 79% in splenectomized subjects given Nplate compared to no splenectomized subjects given placebo (p less than 0.0001). Nplate-treated subjects achieved platelet counts of 50,000 per microliter or more for an average of 13.8 weeks in the splenectomized group and 15.2 weeks in the non-splenectomized group compared with 0.2 and 1.3 weeks for subjects in the respective placebo groups. Significantly more subjects in the placebo group received rescue treatment to increase platelet counts to prevent or treat bleeding compared to the Nplate-treated subjects (57% placebo versus 26% Nplate-treated splenectomized group; 62% placebo versus 17% Nplate-treated non-splenectomized group) (p less than 0.0001). Adverse event rates were similar between the Nplate and placebo groups. A BLA is currently under review by the FDA.
January 7, 2008
Panacos reported preliminary results from a phase IIb trial of bevirimat for the treatment of drug resistant HIV. The subjects received either placebo or bevirimat in combination with their failing antiretroviral therapy. Reported data are from a cohort of nine subjects who received 350 mg of bevirimat solution once daily and two subjects who received placebo, both in addition to their failing background regimen. The treatment duration was fourteen days. A mean viral load reduction of 0.62 log10 was seen in the nine bevirimat-treated patients on day fifteen. Of these subjects, three (33%) had greater than a 0.5 log10 reduction and all had a greater than a 1.0 log10 reduction. Following dosing with 350 mg of bevirimat, the mean trough plasma concentration of bevirimat at steady state was 43.8 micrograms/ml. Overall AUC (Area Under the Curve) exposures to bevirimat were comparable in the 300 and 350 mg cohorts. Based on the results, Panacos planned to move forward with the next cohort, in which treatment-experienced subjects would receive a daily 400 mg bevirimat solution or placebo on top of their failing background regimen, for two weeks.
October 22, 2007
Achellion announced positive interim results from a phase II trial of elvucitabine for the treatment of HIV. This randomized, double-blind study enrolled 78 subjects with wild-type HIV-1 virus. The subjects were placed in two treatment groups to receive elvucitabine (10 mg/day) with efavirenz (600 mg/day) and tenofovir (300 mg/day) or lamivudine (300 mg/day) with efavirenz (600 mg/day) and tenofovir (300 mg/day). All the subjects were treated during a 12-week blinded period after which responders (those with viral loads below 400 copies/mL, or less than 2 log10 decrease) continued to an 84-week open-label extension period. The results at 12 weeks demonstrated that elvucitabine has a potent anti-viral activity similar to lamivudine, with a mean change in HIV-RNA from base-line in the elvucitabine group of -2.7 log10 (+/-0.82) versus -3.0 log10 (+/-0.79) in the lamivudine group. Treatment was safe and well tolerated, with no drug-related adverse events. Achellion expects to report top-line 24-week data by the end of 2007.
September 10, 2007
Avexa released positive interim results from a phase IIb trial of apricitabine (ATC) for the treatment of HIV. This 48-week trial was conducted in three segments. For the first 21 days, subjects received 600 mg or 800 mg ATC twice daily, or continued on lamivudine (3TC), without changing their background drug regimen. At day 21, subjects continued on ATC or 3TC as before, but their background drugs were optimized. At week 24, all subjects were offered open label ATC 800 mg twice daily. At week 24 plasma levels of HIV below the limit of detection (less than 400 copies/mL) were assessed; more than 80% of subjects on either dose of ATC had plasma levels of HIV within this range. In addition, there were CD4 cell increases of 28-39% and 73-86% in the ATC 600 mg and 800 mg arms, respectively. Based on the results, Avexa plans to advance ATC towards phase III development.
August 27, 2007
Intercell released positive interim data from a phase II trial of IC41 for the treatment of hepatitis C virus (HCV). This trial enrolled 50 treatment nave subjects with chronic HCV genotype 1. Subjects received 8 intradermal injections of the IC41 vaccine in bi-weekly intervals for 14 weeks. The primary endpoint is a statistically significant decline in HCV-RNA viral load from baseline. Interim analysis from the first 25 treated subjects showed this endpoint was achieved. In the second week after the final vaccination, a 40 % reduction of viral load (0.2 log) was observed in comparison to the baseline (p=0.0178). In a subset of subjects with high viral load (> 2 million copies/ml) before treatment, a statistically significant average decline of 60 % (0.4 log) was achieved (p=0.0168). Full results and 24 week analysis are expected in early 2008.
Targeted Genetics issued mixed results from a phase II trial of tgAAC09, a vaccine for the treatment of HIV. This double-blind, randomized, placebo-controlled trial enrolled 91 HIV-negative, healthy subjects across five sited in Africa. Subjects received two intra-muscular injections of placebo or tgAAC09 at 3 different dosage levels either six or 12 months apart. The vaccine was well tolerated, with no severe local or systemic reactions reported. However, modest, dose dependent immunogenicity was observed only at the highest dose level, with responses being directed mostly to gag. Presence of neutralizing titers to adeno-associated virus vector 2 (AAV2) at baseline did not appear to impact response to vaccination. Additional phase II trials are ongoing in Africa.
Vical reported positive results from three phase IIa trials of their plasmid DNA HIV vaccine. These studies, dubbed TRIAD, enrolled subjects across several international sites. The trials involved priming an immune response with three doses of a pDNA vaccine over a two month period and boosting the response with a single dose of adenoviral vector vaccine at six months. The vaccine was shown to be safe and well tolerated. It was effective in inducing a T-cell immune responses in up to 70% of the vaccine recipients. Based on the results, Vical plans to move forward with the development of their HIV vaccine.
July 30, 2007
Merck released positive results from an ongoing phase II trial of Isentress for the treatment of HIV. This multi-center, dose-ranging double-blind, randomized trial enrolled 198 treatment-naive HIV subjects who received Isentress (100mg, 200mg, 400mg, or 600 mg; each administered orally twice daily) in combination with tenofovir and lamivudine or 600 mg efavirenz dosed orally once daily in combination with the same agents. The trial was designed to compare Isentress to efavirenz in terms of sustained reductions in HIV viral RNA and improvements in CD4 cell counts from baseline. At 48 weeks, results showed 83% to 88% of subjects receiving the Isentress regimen (all doses studied) maintained reductions in HIV RNA viral load to less than 50 copies/mL. These results were comparable to the efavirenz arm, with 87% of the subjects reaching this endpoint. The mean increase from baseline in CD4 cell counts of the groups receiving Isentress ranged from 144 to 221 cells/uL, and mean increase from baseline in CD4 cell counts of the efavirenz group was 170 cells/uL. A NDA is currently under review by the FDA.
OctoPlus and Biolex announced positive preliminary results from a phase IIa trial of Locteron for the treatment of hepatitis C. This randomized, open-label trial, dubbed SELECT-1 (Safety and Efficacy of Locteron: European Clinical Trial 1), enrolled 32 treatment-naïve subjects infected with hepatitis C genotype-1. Subjects received Locteron, administered subcutaneously once every two weeks in doses of 160, 320, 480 and 640 micrograms (ug), and combined with oral ribavirin, for 12 weeks. A dose dependent response was observed, with the 320 and 480 ug doses of Locteron demonstrating a greater reduction in hepatitis C virus than the 160 ug dose at all measurement times. At 12 weeks the average viral reduction for the 320 and 480 ug doses was 4.5 and 4.2 logs, respectively, compared to 1.8 logs in the lowest dose of 160 ug. In the highest dose groups (320 and 480 ug), 63% of the subjects had an undetectable viral load compared to 13% in the lowest dose group (160 ug) and early virologic response was observed in 88% and 100% of the subjects in the 320 and 480 ug dose groups, respectively, compared to 38% in the 160 ug group. Complete results are expected in Q4, 2007, with phase IIb trials planned to commence in 2008.
Samaritan reported positive preliminary results from a phase IIb trial of SP01A for the treatment of HIV. This double-blind, placebo controlled, multi-dose study enrolled 43 subjects who were placed in three SP01A treatment groups: 200mg (200mg QD), 400mg (200mg BID), and 800mg (400mg BID), for 28 days. This monotherapy study was designed to evaluate SP01A's safety and effect on viral load, with evidence of an increasing viral load at day 11 and day 28. The mean change in viral load as measured from baseline to day 11, showed an increase of 0.3 log10 copies/ml for the 200mg/day dose group, an increase of 0.1 log10 copies/ml for the 400mg/day dose group and a decrease of 0.2 log10 copies/ml for the 800mg/day dose group. At 28 days, the percentage of subjects with a reduction in viral load was 10% for the 200mg/day group, 42% for the 400mg/day group, and 50% for the 800mg/day group. Based on the results, Samaritan plans to advance SP01A into additional trials.
July 16, 2007
Tibotec issued positive results from two phase III trials of TMC125 for the treatment of HIV. These double-blind, placebo-controlled trials, dubbed DUET-1 and DUET-2, enrolled 1.203 subjects internationally. Subjects were randomized to receive TMC125 200 mg twice daily or placebo, each given in addition to a background regimen (BR) consisting of 600 mg darunavir, co-administered with 100 mg ritonavir, twice-daily plus nucleoside reverse transcriptase inhibitors. Results from DUET-1 showed that 56% of the subjects in the TMC125 arm achieved a confirmed undetectable viral load (less than 50 copies/mL), compared to 39% in the placebo arm (p=0.005). In DUET-2, 62% in the TMC125 arm achieved a confirmed undetectable viral load compared to 44% in the placebo arm (p=0.0003). Treatment was generally well tolerated, with rash the most commonly reported adverse event. Tibotec plans to use this data in a NDA filing.
March 12, 2007
Tibotec reported positive interim results from a phase IIb trial of TMC278 for the treatment of HIV. This randomized, partially blinded, controlled trial enrolled 368 treatment-naïve subjects who received three once-daily doses of TMC278 (25 mg, 75 mg, and 150 mg) or efavirenz (600 mg) both in combination with Combivir or Truvada. At 48 weeks 81% (25mg), 80% (75mg) and 77% (150mg) of the subjects reached the primary endpoint of confirmed plasma viral load <50 copies/mL. This was also reached by 81% of the subjects in the efavirenz arm. Based on the results, Tibotec plans to use the 75 mg dose for upcoming phase III trial.
September 11, 2006
Genvec issued positive results from two phase I studies of HIV vaccine incorporating GenVec's adenovector-based technology. In the first study 40 subjects received the vaccine in a single dose of either 1e10 Particle Units (PU) or 1e11 PU. At both doses the vaccine was well tolerated and stimulation of T-cells against the multiple antigens contained in the vaccine occurred. In the second study 14 subjects were given a DNA prime followed by a boost with the HIV vaccine. Data revealed that the prime-boost combination produced more polyfunctional T-cells than either treatment alone. Based on these results Genvec plans to move development of the vaccine forward.
November 17, 2003
VaxGen reported negative results from a phase III trial investigating AIDSVAX B/E (rgp 120), a vaccine for the prevention of HIV infection. Results showed the vaccine did not show efficacy for either primary or secondary endpoints. Results showed that 105 subjects who received placebo became infected with HIV compared with 106 subjects who received AIDSVAX B/E. The vaccine appeared to be well tolerated with no serious adverse events reported. The randomized, double-blind, placebo-controlled study enrolled 2,546 intravenous drug users at 17 sites in Bangkok, Thailand. The trial was designed to evaluate the vaccine against the blood-borne transmission of HIV subtype E and one strain of HIV subtype B. Subjects were given a total of seven injections, administered at months 0, 1, 6, 12, 18, 24 and 30.
February 24, 2003
Gilead Sciences reported positive results from a phase III trial comparing Viread (tenofovir disoproxil fumarate), a nucleotide analogue reverse transcriptase inhibitor to stavudine for the treatment of HIV infection. Results showed that subjects who received Viread experienced less lipodystrophy, lower elevations in fasting cholesterol and triglyceride levels, and similar reductions in viral load compared to stavudine. Data revealed that 82% of subjects treated with Viread achieved an HIV RNA reduction of less than 400 copies/ml compared to 78% of subjects treated with stavudine. Study 903 is an ongoing, randomized, double blind trial designed to compare the efficacy and safety of Viread plus lamivudine/efavirenz to stavudine plus lamivudine/efavirenz in 600 antiretroviral-naïve subjects with HIV infection.
Vertex Pharmaceuticals reported positive results from two-phase III trials investigating GW433908 (908), a protease inhibitor for the treatment of HIV/AIDS. In the NEAT trial, results showed that 66% of 166 subjects achieved an undetectable viral load (vRNA) with 908 compared to 51% of 83 subjects who received the alternative treatment nelfinavir. Data showed that 28% of subjects who received nelfinavir were considered virologic failures compared to 14% of subjects with 908. In addition, 55% of subjects in the 908 group achieved a viral load less than 50 copies/ml compared to 41% of subjects in the nelfinavir group. The open-label, randomized, multi-center study called NEAT enrolled 249 HIV-positive subjects. Subjects were treated with either 1400 mg 908 or 1250 mg of nelfinavir twice daily for 48 weeks. Positive preliminary results were also reported from the CONTEXT trial comparing 908 plus Ritonavir to Lopinavir plus Ritonavir in 320 treatment-experienced subjects.
August 19, 2002
Results of a large observational cohort study comparing anti-HIV combination treatment regimens containing Sustiva (efavirenz) or Viramune (nevirapine) in 1,078 subjects with treatment-naïve HIV showed that the Sustiva arm was significantly more effective with regard to the primary endpoint of time to treatment failure. The Viramune group failed more rapidly (303 days) than did the Sustiva group (589 days). In addition, subjects receiving the regimen containing Sustiva showed a significantly greater log decrease in plasma HIV-1 RNA than did the subjects with the Viramune therapy. Finally, 51% of subjects receiving Sustiva maintained a viral load of less than 400 copies/mL, compared to 45% of the Viramune group maintaining a similar viral load. Sustiva, a non-nucleoside reverse transcriptase inhibitor (NNRTI), is a product of Bristol-Myers Squibb.
July 22, 2002
Preliminary phase II trial results indicate that Hollis-Eden Pharmaceuticals' HE2000 produces increases in a number of beneficial cell types, as well as a reduction in HIV viral burden. The placebo-controlled trial included 24 treatment-naïve HIV-infected subjects. Subjects received subcutaneous injections of placebo or 50 or 100 mg HE2000 for five consecutive days, with the cycle repeating every six weeks. Subjects were also followed for an additional 12 weeks after the last dosing cycle. For the 50-mg dose group, results showed a statistically significant downward slope in viral load versus placebo during the study period. Subjects receiving HE2000 also experienced increases in various cell types associated with innate and adaptive cell-mediated immunity, including killer cells, dendritic cells and Th1 cells. In contrast, cell levels in the placebo group generally declined over the duration of the study.
Study results indicate that switching from the protease inhibitor nelfinavir to Bristol-Myers Squibb's atazanavir may significantly reduce cardiovascular risk factors in subjects with HIV. At 12 weeks, the switch was associated with significant reductions compared to baseline levels in total cholesterol, LDL cholesterol and triglycerides, in addition to an increase in HDL cholesterol. The switch also decreased the proportion of subjects with undesirable levels of total cholesterol (from 32% to 10%) and LDL cholesterol (from 55% to 22%).
May 13, 2002
Preliminary 48-week phase III trial results indicate that a regimen containing Gilead Sciences' Viread (tenofovir disoproxil fumarate) was comparable to a stavudine-containing regimen in treating HIV subjects naïve to therapy. The three-year, randomized, double-blind, 600-subject trial compared the efficacy of a treatment regimen containing Viread, lamivudine and efavirenz to a regimen containing stavudine, lamivudine and efavirenz. In an analysis of the intent-to-treat population, 87% of subjects in both the Viread- and stavudine-treated groups achieved suppression of HIV RNA below 400 copies/mL at 48 weeks of treatment. Additionally, 82% of subjects in the Viread arm achieved HIV RNA suppression below 50 copies/mL, compared to 81% of subjects in the stavudine arm. Subjects in both treatment groups experienced significant increases in CD4 cell count.
April 22, 2002
Phase III 24-week data indicates that T-20 plus an individualized antiretroviral treatment regimen provides an additional decrease in virus level compared to an antiretroviral treatment regimen alone. The open-label, randomized "TORO 1" trial included 491 HIV-1 infected subjects who were treatment-experienced and/or had documented resistance to the three classes of currently available antiretrovirals. Subjects who received T-20 achieved a reduction in HIV levels of 1.697 log10 copies/mL versus 0.763 log10 copies/mL for the control arm. Between the two study arms, the difference in the magnitude of decrease in HIV (the primary efficacy endpoint) was statistically significant at 0.934 log10 copies/mL. T-20 is being developed by Hoffmann-La Roche and Trimeris.