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Data from Viral Kinetic Study Showed Rapid Reduction of HCV RNA with ALS-2200 (VX-135), Vertex’s Oral Nucleotide Analogue in

  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

 - 4.54 log[10] median reduction in HCV RNA after 7 days of dosing; ALS-2200
was well-tolerated with no serious adverse events and no discontinuations due
                             to adverse events -

 - Vertex moving forward with multiple Phase 2 trials in early 2013 exploring
 all-oral combinations, including VX-135 with GSK2336805 and with simeprevir
                                  (TMC435) -

Business Wire

BOSTON -- November 10, 2012

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 log[10] 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 adverse events. 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 coming weeks.

“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 log[10 ]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
(β or γ) 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 inhibitors.

“Analysis of ALS-2200, a novel potent nucleotide analog, combination drug
interactions in the hepatitis C virus (HCV) subgenomic replicon system.”

Poster presentation #1887

November 13, 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 genotypes, 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 program.

About INCIVEK

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 combination therapy.

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
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^®.

IMPORTANT SAFETY INFORMATION

Indication

INCIVEK^® (telaprevir) is a prescription medicine used with the medicines
peginterferon alfa and ribavirin to treat chronic (lasting a long time)
hepatitis C genotype 1 infection in adults with stable liver problems, who
have not been treated before or who have failed previous treatment. It is not
known if INCIVEK is safe and effective in children under 18 years of age.

Important Safety Information

INCIVEK should always be taken in combination with peginterferon alfa and
ribavirin. Ribavirin may cause birth defects or death of an unborn baby.
Therefore, a patient should not take INCIVEK combination treatment if she is
pregnant or may become pregnant, or if he is a man with a sexual partner who
is pregnant. Patients must use two forms of effective birth control during
treatment and for the 6 months after treatment with these medicines. Hormonal
forms of birth control, including birth control pills, vaginal rings, implants
or injections, may not work during treatment with INCIVEK.

INCIVEK and other medicines can affect each other and can also cause side
effects that can be serious or life threatening. There are certain medicines
patients cannot take with INCIVEK combination treatment. Patients should tell
their healthcare providers about all the medicines they take, including
prescription and non-prescription medicines, vitamins and herbal supplements.

INCIVEK can cause serious side effects including skin reactions, rash and
anemia that can be severe. The most common side effects of INCIVEK include
itching, nausea, diarrhea, vomiting, anal or rectal problems, taste changes
and tiredness. There are other possible side effects of INCIVEK, and side
effects associated with peginterferon alfa and ribavirin also apply to INCIVEK
combination treatment. Patients should tell their healthcare providers about
any side effect that bothers them or doesn't go away.

Please see full Prescribing Information for INCIVEK including the Medication
Guide, available at www.INCIVEK.com.

About Hepatitis C

Hepatitis C is a serious liver disease caused by the hepatitis C virus, which
is spread through direct contact with the blood of infected people and
ultimately affects the liver.^1 Chronic hepatitis C can lead to serious and
life-threatening liver problems, including liver damage, cirrhosis, liver
failure or liver cancer.^1 Though many people with hepatitis C may not
experience symptoms, others may have symptoms such as fatigue, fever, jaundice
and abdominal pain.^1 Unlike HIV and hepatitis B virus, chronic hepatitis C
can be cured.^2 If treatment is not successful and a person does not achieve a
viral cure, they remain at an increased risk for progressive liver
disease.^3,4

More than 170 million people worldwide are chronically infected with hepatitis
C.^5 In the United States, up to 5 million people have chronic hepatitis C and
75 percent of them are unaware of their infection.^6,7 Hepatitis C is four
times more prevalent in the United States compared to HIV.^7 The majority of
people with hepatitis C in the United States were born between 1945 and 1965,
accounting for 82 percent of people with the disease.^8 Hepatitis C is the
leading cause of liver transplantations in the United States and is reported
to contribute to 15,000 deaths annually.^9,10 By 2029, total annual medical
costs in the United States for people with hepatitis C are expected to more
than double, from $30 billion in 2009 to approximately $85 billion.^11

About Vertex

Vertex creates new possibilities in medicine. Our team discovers, develops and
commercializes innovative therapies so people with serious diseases can lead
better lives.

Vertex scientists and our collaborators are working on new medicines to cure
or significantly advance the treatment of hepatitis C, cystic fibrosis,
rheumatoid arthritis and other life-threatening diseases.

Founded more than 20 years ago in Cambridge, Mass., we now have ongoing
worldwide research programs and sites in the U.S., U.K. and Canada. Today,
Vertex has more than 2,000 employees around the world, and for three years in
a row, Science magazine has named Vertex one of its Top Employers in the life
sciences

Vertex's press releases are available at www.vrtx.com.

Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the
Private Securities Litigation Reform Act of 1995, including, without
limitation, the statements of Dr. Kauffman, Dr. Marcellin and Dr. Blatt and
statements about Vertex’s expectations regarding the timing and structure of
multiple Phase 2 studies exploring all-oral treatment regimens that include
VX-135 in combination with GSK2336805, TMC435, ribavirin or INCIVEK. While the
company believes the forward-looking statements contained in this press
release are accurate, there are a number of factors that could cause actual
events or results to differ materially from those indicated by such
forward-looking statements. Those risks and uncertainties include, among other
things, that the initiation of Phase 2 studies of VX-135 may be delayed or
prevented, outcomes from any future studies of VX-135 may not be favorable and
the other risks listed under Risk Factors in Vertex's annual report and
quarterly reports filed with the Securities and Exchange Commission and
available through Vertex's website at www.vrtx.com. Vertex disclaims any
obligation to update the information contained in this press release as new
information becomes available.

(VRTX-GEN)

References:

^1 Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC
Viral Hepatitis. Available at:
http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf Updated June
2010. Accessed September 21, 2012.

^2 Pearlman BL and Traub N. Sustained Virologic Response to Antiviral Therapy
for Chronic Hepatitis C Virus Infection: A Cure and So Much More. Clin Infect
Dis. 2011 Apr;52(7):889-900.

^3 Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of
sustained virological responders and non-responders in the Hepatitis C
Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology.
2008;50(Suppl 4):357A (Abstract 115).

^4 Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and
clinical outcomes in patients with chronic hepatitis C and advanced fibrosis.
Annals of Internal Medicine. 2007; 147: 677-684.

^5 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and
treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.

^6 Chak, E, et. al. Hepatitis C Virus Infection In USA: An Estimate of True
Prevalence. Liver Intl. 2011;1096 -1098.

^7 Institute of Medicine of the National Academies. Hepatitis and liver
cancer: a national strategy for prevention and control of hepatitis B and C.
Colvin HM and Mitchell AE, ed. Available at:
http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx
Updated January 11, 2010. Accessed September 21, 2012.

^8 Smith, BD, et al. Hepatitis C Virus Antibody Prevalence, Correlates and
Predictors among Persons Born from 1945 through 1965, United States,
1999-2008. AASLD 2011 Annual Meeting.

^9 Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral
therapy for hepatitis C in the United States. Hepatology.
2009;50(6):1750-1755.

^10 Ly KN, et al. The Increasing Burden of Mortality From Viral Hepatitis in
the United States Between 1999 and 2007. Ann Intern Med. 2012;156:271-278.

^11 Pyenson B, Fitch K, and Iwasaki K. Consequences of Hepatitis C Virus
(HCV): Costs of a Baby Boomer Epidemic of Liver Disease. Milliman, Inc. May
2009. Available at: http://www.vrtx.com/assets/pdfs/MillimanReport.pdf

Contact:

Vertex Pharmaceuticals Incorporated
Media:
Erin Emlock or Dawn Kalmar, 617-444-6992
mediainfo@vrtx.com
or
Investors:
Kelly Lewis, 617-961-7530
or
Michael Partridge, 617-341-6108
 
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