VX-135 is a uridine nucleotide analogue pro-drug designed to inhibit the replication of the
hepatitis C virus by acting on the NS5B polymerase. Vertex gained worldwide rights to
ALS-2200, known as VX-135 in Phase 2 studies, through an exclusive licensing agreement
signed with Alios BioPharma, Inc. in June 2011.
(VX-135) is still on partial clinical hold by the FDA in the U.S. - Vertex’s VX-135 partial hold
May 1 2014
Vertex ends hepatitis C investment as sales fall
Vertex said it will license an experimental hepatitis C drug called VX-135 to Alios BioPharma. Revenue from Incivek dropped almost 90 percent in the first quarter as the drug was supplanted by newer treatments and Vertex sold its overseas marketing rights.
EASL: An Interferon- and Ribavirin-Free 12-Week Regimen of Once-Daily VX-135 and Daclatasvir in Treatment-Naïve Patients With Genotype 1 HCV Infection - (04/16/14)
Hepatitis C: Vertex Announces VX-135 with Daclatasvir (SVR4) Data
(VX-135) is still on partial clinical hold in the U.S.
VX-135, A Once-daily Nucleotide HCV Polymerase Inhibitor, Was Well Tolerated And Demonstrated Potent Antiviral Activity When Given With Ribavirin In Treatment-naïve Patients With Genotype 1 HCV
Aug 27 2013
Vertex’s VX-135 partial hold signals heightened FDA scrutiny toward HCV drugs
The FDA seems to be very sensitive about any compounds causing hepatotoxicity (liver damage) in HCV, said one
expert, a US-based investigator. There is now a lot of focus on cardiac and hepatotoxicity due to Bristol-Myers
Squibb’s (NYSE:BMY) failed purine nuc, he said. BMS suspended BMS-986094 in August 2012 following cardiac
toxicity, which resulted in a patient death in a Phase II trial. The drug had been purchased in its USD 2.5bn
The partial hold indicates the FDA is very sensitive about hepatotoxicity, even if it means making the development
path more difficult, the US expert added.
Any adverse events have to be mitigated to a new degree, as a lot of drugs seem to be emerging without adverse
events, a second US expert noted. The problem with any liver enzyme elevation is that there are many good drugs
in the pipeline now, agreed a European expert....
July 25 2013
VX-135 -Vertex Sees Liver Toxicity With Emerging Hep C Drug, Faces FDA Hold
U.S. Study: FDA places partial clinical hold on ongoing Phase 2 U.S. study of VX-135, preventing
evaluation of 200 mg dose following observation of elevated liver enzymes in patients receiving
400 mg of VX-135 in combination with ribavirin in Phase 2 study in Europe; evaluation of 100 mg dose
continues in U.S.-
April 28 2013
EASL: Vertex announced new data from viral kinetic study of ALS-2200 (VX-135)
ALS-2200, A Novel Once-daily Nucleotide HCV Polymerase Inhibitor, Demonstrated Potent Antiviral Activity In Treatment-naïve Patients with Compensated Cirrhosis or Genotype 2-4 Chronic Hepatitis C
VX-135/daclatasvir: Vertex signs agreement with Bristol-Myers for all-oral midstage studies for hepatitis C
Vertex Pharmaceuticals Inc. (VRTX) entered a nonexclusive agreement with Bristol-Myers Squibb Co. (BMY) to conduct midstage studies for hepatitis C treatments, its latest collaboration as part of its push
to develop treatments for the liver disease.
The Phase 2 studies are for once-daily all-oral treatment regimens containing Vertex's nucleotide
analogue hepatitis C virus polymerase inhibitor VX-135 and Bristol-Myers Squibb's NS5A replication complex inhibitor daclatasvir.
As part of the agreement, Vertex plans to conduct two Phase 2 studies of the combination, including an initial study in
treatment-naive people with genotype 1 hepatitis C virus, planned for the second quarter.
Vertex plans to begin a subsequent study in treatment-naive people infected with genotype 1, 2 or 3
hepatitis C virus, including those with cirrhosis, in the second half, pending data from the initial study.
Jan 7 2013
Vertex's strategy in hepatitis C is to develop new all-oral treatment regimens
VX-135 in Combination with Ribavirin
-- In the first quarter of 2013, Vertex expects to begin dosing in a study of VX-135 and ribavirin as part
of a 12-week all-oral treatment regimen. The study will evaluate safety,tolerability and
viral cure rates (SVR12; undetectable hepatitis C virus 12 weeks after the end of treatment)....
Data from Viral Kinetic Study Showed Rapid Reduction of HCV RNA with
ALS-2200 (VX-135), Vertex's Oral Nucleotide Analogue in Development for the
Treatment of Hepatitis C
BOSTON --(Business Wire)-- Vertex Pharmaceuticals
Incorporated (Nasdaq: VRTX) today announced that data on ALS-2200 (VX-135), an
oral medicine Vertex is developing for the treatment of hepatitis C, are being
presented for the first time at The Liver Meeting®, the 63rd Annual Meeting of the
American Association for the Study of Liver Diseases (AASLD).
There was a median 4.54 log10 reduction (range -3.81, -5.08) in hepatitis C virus (HCV) RNA
after seven days of dosing with ALS-2200 (200 mg) once daily in people with genotype 1 chronic
hepatitis C who were new to treatment (n=8). Similar reductions in HCV RNA were seen in a seven-day
viral kinetic study of once daily ALS-2200 (200 mg) in combination with ribavirin (n=8). ALS-2200
was well-tolerated in this study, with no serious adverse events and no discontinuations due to
Based on these data, and to further characterize the medicine's safety and efficacy profile,
Vertex plans to begin multiple Phase 2 studies of 12-week all-oral regimens in
people with genotype 1 hepatitis C in early 2013, pending discussions with
regulatory authorities. These studies will include combinations of VX-135 with
GSK2336805 and separately with simeprevir (TMC435). Upon the start of Phase 2
studies, ALS-2200 will be known as VX-135. Screening in the first study, which
will evaluate VX-135 in combination with ribavirin, is expected to begin in the
"We're working quickly to evaluate multiple all-oral treatment regimens
with VX-135 and expect to have a significant amount of data
from several Phase 2 studies by the end of 2013," said Robert Kauffman, M.D.,
Ph.D., Senior Vice President and Chief Medical Officer at Vertex. "Our goal is
to proceed to pivotal development with one or more regimens that have the
greatest potential to offer doctors and the people they treat a more tolerable,
short-duration therapy with high viral cure rates for hepatitis C."
Seven-day viral kinetic data showed that when once-daily ALS-2200 (200 mg) was
dosed in combination with ribavirin, there was a median 4.18 log10
reduction (range -3.6, -5.2) in HCV RNA in people with genotype 1
chronic hepatitis C who were new to treatment (n=8). Five patients achieved HCV
RNA levels below the limit of quantification (< LOQ = < 25 IU/mL), and
two of these five achieved HCV RNA levels below the limit of detection (Roche
COBAS Taqman HCV test, Version 2) after seven days of dosing. Similar to the
data from the monotherapy cohort, ALS-2200 in combination with ribavirin was
well-tolerated, no patients discontinued due to adverse events and there were
no serious adverse events.
"The early antiviral activity and tolerability of this nucleotide analogue are very
promising as we seek to develop new interferon-free treatment regimens," said
Patrick Marcellin, M.D., Ph.D., Professor of Hepatology at the University of Paris
and Head of the Viral Hepatitis Research Unit in Hôpital Beaujon, Clichy.
"The data suggest VX-135 could be a core component of all-oral regimens for the
treatment of hepatitis C."
"Preclinical characterization of ALS-2200, a potent nucleotide polymerase inhibitor
for the treatment of chronic hepatitis C."
Poster presentation #1882
November 13, 2012, 8:00 a.m. - 12:00 p.m. EST
Preclinical data on ALS-2200 will be presented at AASLD that support
the Phase 1 viral kinetic study and further clinical development plans. In
preclinical studies, ALS-2200 was shown to be a potent, selective, specific,
and pan-genotypic nucleotide analogue that inhibits the HCV NS5B polymerase.
Specifically, there was no in vitro inhibition of non-HCV viruses, human
DNA (ß or ?) or RNA (II) polymerases, or mitochondrial protein synthesis. The
studies also showed that ALS-2200 retains potency in vitro against a
panel of HCV variants resistant to NS3/4A, NS5A and non-nucleoside NS5B
"Analysis of ALS-2200, a novel potent nucleotide analog, combination drug
interactions in the hepatitis C virus (HCV) subgenomic replicon system."
Poster presentation #1887
2012, 8:00 a.m. - 12:00 p.m. EST
Combination studies with ALS-2200 were performed in vitro to determine whether interactions
with other drugs were additive, synergistic or antagonistic. Combination of ALS-2200 with either
telaprevir or VX-222 demonstrated a synergistic effect, and combination with
ribavirin resulted in an additive response. No significant cytotoxicity or
antagonism were observed at any concentration of the combinations tested.
Combinations of ALS-2200 and 18 other compounds were also tested, including
simeprevir, which showed significant synergy with ALS-2200.
"We're pleased with the strength of our collaboration with Vertex and how it may lead to
advances in the treatment of hepatitis C," said Lawrence M. Blatt, Ph.D.,
Founder, President and Chief Executive Officer of Alios BioPharma. "We're
looking forward to seeing the results of several studies evaluating various
all-oral combinations including VX-135."
VX-135 Phase 2 Trials
Vertex recently announced that it has entered into two
non-exclusive agreements to conduct Phase 2 proof-of-concept studies of VX-135
in combination with simeprevir (TMC435), a protease inhibitor being jointly
developed by Janssen R&D Ireland and Medivir AB, and with GSK2336805, an
NS5A inhibitor in development by GlaxoSmithKline (GSK). The studies with
GSK2336805 and simeprevir are expected to begin in early 2013, pending
discussions with regulatory authorities. Screening is expected to begin in the
coming weeks for a Phase 2 study of VX-135 and ribavirin. Vertex also plans to
begin a study of VX-135 and telaprevir, the company's approved protease
inhibitor marketed as INCIVEK®(telaprevir) tablets for people with chronic genotype
1 hepatitis C, in early 2013, pending discussions with regulatory authorities.
All of these Phase 2 studies will evaluate safety, tolerability and viral cure
rates (SVR12; undetectable hepatitis C virus 12 weeks after the end of
treatment) using 12-week combination regimens.
About VX-135 (ALS-2200)
VX-135 (ALS-2200) is a uridine nucleotide analogue pro-drug
that appears to have a high barrier to drug resistance based on in vitro
studies. It is designed to inhibit the replication of the hepatitis C virus by
acting on the NS5B polymerase. In vitro studies of the compound showed
antiviral activity across all genotype, or forms, of the hepatitis C virus,
including genotypes more prevalent outside of the United States.
Vertex gained worldwide rights to ALS-2200 through an exclusive worldwide licensing
agreement signed with Alios BioPharma, Inc. in June 2011. The agreement also
includes a research program that focuses on the discovery of additional
nucleotide analogues that act on hepatitis C polymerase. Vertex has the option
to select additional compounds for development emerging from the research
INCIVEK® (telaprevir) tablets is an oral medicine that acts directly on the hepatitis C virus
protease, an enzyme essential for viral replication. INCIVEK has been prescribed to more
than 50,000 patients in the United States.
Approximately three out of four U.S. patients who are prescribed a direct-acting
antiviral for the treatment of genotype 1 chronic hepatitis C (HCV) receive INCIVEK
In Phase 3 clinical studies, 79 percent of people who had not previously been treated
for HCV achieved a viral cure following treatment with INCIVEK combination therapy,
compared with 46 percent of those who received pegylated-interferon and
ribavirin (P/R) alone. Among people who were treated previously but did not
achieve a viral cure, in the Phase 3 studies: 86 percent of relapsers achieved
a viral cure with INCIVEK combination therapy compared to 22 percent with P/R
alone; 59 percent of partial responders achieved a viral cure compared with 15
percent with P/R alone; and 32 percent of null responders achieved a viral cure
compared with 5 percent with P/R alone. In addition, many people are eligible
to complete treatment with INCIVEK combination therapy in 24 weeks - half the
time required for P/R alone.
INCIVEK was approved by the U.S. Food and Drug Administration (FDA) in May 2011
and by Health Canada in August 2011 for use in combination with pegylated-interferon
and ribavirin for adults with genotype 1 chronic hepatitis C with compensated liver
disease (some level of damage to the liver but the liver still functions), including cirrhosis
(scarring of the liver). INCIVEK is approved for people who are new to
treatment, and for people who were treated previously with interferon-based
treatment but who did not achieve a sustained viral response, or viral cure
(relapsers, partial responders and null responders).
Vertex developed telaprevir in collaboration with Janssen and Mitsubishi
(News - Alert) Tanabe Pharma. Vertex has rights to commercialize telaprevir in North
America where it is being marketed under the brand name INCIVEK (in-SEE-veck).
Janssen has rights to commercialize telaprevir in Europe, South America, Australia, the
Middle East and certain other countries. In September 2011, telaprevir was approved in the European
Union and Switzerland. Telaprevir is known as INCIVO® in Europe. Mitsubishi Tanabe Pharma has rights to
commercialize telaprevir in Japan and certain Far East countries. In September
2011, telaprevir was approved in Japan and is known as Telavic®.