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).
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.
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.
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.
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.
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.
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 26, 2002
Results of a phase II study of Remune in combination with highly active antiretroviral therapy (HAART) showed that five out of seven subjects who completed the full treatment period of 132 weeks were responders with higher CD4+ counts. In this clinical study, subjects taking Remune also showed slower rate of progression to AIDS. The study, which took place in Thailand, involved 40 weeks of treatment with Remune alone, followed by 40 weeks of treatment with Remune plus HAART, followed by another period in which HAART was discontinued for structured treatment interruption (STI) and treatment with Remune occurred every 12 weeks. In a separate patient cohort study of Remune and Remune plus HAART, the 20 study subjects showed no signs of resistance mutation over a 232-week observation period. Remune is being developed by Trinity Medical Group USA.
July 15, 2002
Phase II/III trial results suggest that Serono S.A.'s Serostim (somatropin for injection) reduces adipose tissue maldistribution in subjects with HIV-associated adipose redistribution syndrome (HARS). The double-blind STARS trial included 239 subjects at trial sites located throughout the United States. Subjects were randomized to receive Serostim 4 mg daily, Serostim 4 mg on alternate days or placebo. Results showed that Serostim 4 mg daily (versus placebo) produced a significant decrease in visceral adipose tissue (VAT) from baseline to week 12. Additionally, the trunk to limb fat ratio was significantly reduced in both the Serostim 4 mg daily and alternate day groups compared to placebo.