Phase II, 24-Week Results for Vertex's Merimepodib Presented at the Annual HEP DART Conference

[Guest guest]

Phase II, 24-Week Results for Vertex's Merimepodib Presented at the Annual

HEP DART Conference

VERTEX PHARMACEUTICALS JOSHUA BOGER

Dr. Boger, chairman and CEO, Vertex Pharmaceuticals Incorporated.

Press Contact: Michele Karpf Belansky, corporate communications,

617-444-6259.

CAMBRIDGE, MA USA 07/23/2002

CAMBRIDGE, Mass., Dec. 17 /PRNewswire-FirstCall/ -- An investigational

new

drug, merimepodib (VX-497), enhances the antiviral effect of pegylated-

interferon (peg-IFN) and ribavirin at 24 weeks of treatment in hepatitis C

virus (HCV) patients who were non-responsive to treatment with a previous

course of interferon-alfa and ribavirin, according to results presented at

the

HEP DART 2003 Frontiers in Drug Development for Therapies for Viral

Hepatitis

in Kauai, Hawaii. Merimepodib is an oral therapy for the treatment of HCV

being developed by Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX).

Vertex

retains worldwide commercial rights to merimepodib and is now planning to

initiate additional studies with merimepodib, including a first pivotal

study,

in hepatitis C patients in 2004.

The data from the core study period, presented at HEP DART, indicate

that

the triple combination of merimepodib, peg-IFN and ribavirin was well

tolerated and led to a statistically significant, dose-dependent increase in

the proportion of patients with undetectable levels of hepatitis C virus (<

50

IU/mL; approximately < 100 copies/mL) after 24 weeks of treatment. The

study

enrolled patients with genotype 1 HCV, which is the most common viral strain

and which is associated with the lowest response to combination therapy.

" Genotype 1 hepatitis C patients who are refractory to the combination

therapy of interferon and ribavirin represent a very difficult-to-treat

patient population and typically show limited, if any, viral response upon

re-

treatment, " stated Dr. Marcellin, Professor of Medicine at

University

of Paris VII, and the lead investigator for the study. " While the study was

designed primarily for an analysis of safety and tolerability, the

additional

antiviral activity observed with merimepodib at 24 weeks is encouraging. "

" Merimepodib represents a potentially important near-term treatment

advance in chronic hepatitis C as part of a combination therapy approach

that

may increase the ability of patients to achieve viral clearance, " stated

J. Alam, M.D., Senior Vice President of Drug Evaluation and Approval. " The

formal presentation of these Phase II, 24-week results affirms our

commitment

to rapidly advance the clinical development of merimepodib. These results

will help to guide the clinical path of merimepodib going forward in 2004. "

Study Design

The Phase II, double-blind, placebo-controlled, randomized study

reported

today was designed to evaluate the safety and tolerability of two dose

regimens of merimepodib (MMPD) in combination with peg-IFN and ribavirin in

patients with HCV genotype 1 who were non-responsive to interferon-alfa and

ribavirin therapy. Non-response was defined as at least 12 weeks of prior

treatment with documented, detectable HCV-RNA at the end of the treatment

period. The secondary objective of the study was to assess the

pharmacokinetics and clinical activity of merimepodib. The trial enrolled

31

patients who were treated with 25 mg MMPD, 50 mg MMPD, or placebo twice

daily

(BID) in combination with standard doses of peg-IFN and ribavirin for 24

weeks. Following the 24-week core study, patients who were HCV-RNA

undetectable continued on assigned treatment for an additional 24 weeks in

an

extension phase. Collection of 48-week end-of-treatment data and six-month

post-treatment sustained virologic response data is continuing.

Safety Results

Study results showed that merimepodib was well tolerated through 24

weeks

of treatment. Adverse events that appeared most closely associated with

merimepodib were diarrhea, abdominal pain, and mild rash, which occurred in

none of the patients in the placebo group and in 18% to 24% of patients in

the

merimepodib treatment groups. Injection site inflammation as a result of

peg-

IFN appeared to be less common in patients treated with merimepodib.

Additionally, merimepodib did not appear to exacerbate the incidence of

hematological toxicities associated with peg-IFN and ribavirin treatment.

Total bilirubin levels were similar across groups, suggesting there was no

increase in the incidence of hemolytic anemia that is associated with

ribavirin. The majority of adverse events reported were consistent with the

known side effect profile for peg-IFN and ribavirin treatment, and the

addition of merimepodib did not appear to increase the clinical severity of

these events.

Efficacy Results

Study results showed that, relative to placebo, merimepodib treatment

produced a statistically significant, dose-dependent increase in the

percentage of patients who achieved undetectable levels of HCV-RNA at 24

weeks. The three treatment groups had comparable levels of baseline

HCV-RNA.

At 24 weeks, 86% (6 of 7 patients) of patients receiving 50 mg MMPD BID had

undetectable levels of HCV-RNA, compared to 33% (2 of 6) of patients

receiving 25 mg MMPD BID and 33% (3 of 9) of patients receiving placebo (p =

0.03; Jonckheere-Terpstra test for increasing dose response among patients

on-

treatment at week 24). The on-treatment analysis of the percentage of

patients who were HCV-RNA undetectable at week 24 was the primary clinical

activity endpoint in the study. Analysis of all patients randomized

(intent-

to-treat population; ITT) also revealed a statistically significant, dose-

dependent antiviral effect. Seventy-three percent (8 of 11 patients)

receiving 50 mg MMPD BID achieved undetectable levels of HCV-RNA on at least

one occasion during the study, compared to 20% (2 of 10) of patients

receiving

25 mg MMPD BID and 30% (3 of 10) of the placebo group (p = 0.02; Jonckheere-

Terpstra test for increasing dose response). All patients received

pegylated-

interferon and ribavirin, on a weight-adjusted basis, in addition to the

randomized treatment.

Additionally, data suggested that, compared to baseline, patients

treated

with merimepodib showed a decline in alanine aminotransferase (ALT), a

marker

of liver inflammation. Baseline ALT levels were similar across all three

treatment groups. At 24 weeks, median ALT was lower among patients

receiving

50 mg MMPD BID (18.5 IU/L) than patients receiving 25 mg MMPD BID (41.0

IU/L)

or placebo (45.0 IU/L).

Clinical Need and Market Opportunity in HCV Infection

HCV infection is a serious disease that causes inflammation of the

liver,

which may lead to fibrosis and cirrhosis, liver cancer, and ultimately,

liver

failure. Chronic hepatitis C infection afflicts approximately 2.7 million

people in the U.S., many of whom are unaware of their infected status.

Current treatments provide a sustained viral response for only 40 to 50

percent of patients chronically infected with genotype 1 HCV, the most

difficult viral strain to treat and the most common form in the U.S.

Patients

who are non-responsive to current HCV therapy have limited treatment

options,

and clinical experience shows that only a very low proportion of such

patients

achieve a sustained viral response with subsequent treatment regimens. HCV

may go undetected for up to 20 years following initial infection.

Worldwide,

the disease strikes as many as 185 million people. Each year, 8,000 to

10,000

people in the U.S. die from complications of HCV.

Background on Merimepodib

Merimepodib is a small molecule, orally administered inhibitor of the

enzyme inosine monophosphate dehydrogenase (IMPDH). IMPDH inhibition may

represent an attractive strategy for increasing the sustained viral response

rate in HCV patients, the principal goal of treatment. IMPDH inhibition

leads

to a reduction in intracellular guanosine triphosphate (GTP), a cellular

molecule required by viruses for replication. Recent reports in the medical

literature suggest that IMPDH inhibitors such as merimepodib may enhance the

antiviral activity of ribavirin in vitro by depleting GTP and increasing the

rate of incorporation of ribavirin into viral RNA, rendering the virus

nonfunctional. The antiviral activity observed clinically when merimepodib

is

added to ribavirin-containing HCV therapies is consistent with these

preclinical findings.

About Vertex

Vertex Pharmaceuticals Incorporated is a global biotechnology company

committed to the discovery and development of breakthrough small molecule

drugs for serious diseases. The Company's strategy is to commercialize its

products both independently and in collaboration with major pharmaceutical

partners. Vertex's product pipeline is principally focused on viral

diseases,

inflammation, autoimmune diseases and cancer. Vertex co-promotes the new

HIV

protease inhibitor, Lexiva, with GlaxoKline.

This press release may contain forward-looking statements, including

statements that (i) merimepodib has the potential to increase the ability of

patients to achieve HCV viral clearance, based on 24-week clinical results;

(ii) merimepodib holds promise as part of combination therapy for HCV

patients

who have limited treatment options and represents an attractive commercial

opportunity for Vertex; and (iii) further clinical study of merimepodib will

be initiated in 2004. While management makes its best efforts to be

accurate

in making forward-looking statements, such statements are subject to risks

and

uncertainties that could cause Vertex's actual results to vary materially.

These risks and uncertainties include, among other things, the risks that

clinical trials for merimepodib may not proceed as planned due to technical,

scientific, or patient enrollment issues, that final results from clinical

trials with merimepodib will not reflect positive interim results and other

risks listed under Risk Factors in Vertex's form 10-K filed with the

Securities and Exchange Commission on March 31, 2003.

Lexiva is a registered trademark of the GlaxoKline group of

companies.

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

Vertex Contacts:

Partridge, Director, Corporate Communications (617) 444-6108

Jaren Irene Madden, Media Relations Specialist, Corporate

Communications

(617) 444-6750

SOURCE Vertex Pharmaceuticals Incorporated

Web Site: http://www.vrtx.com

Photo Notes: NewsCom:

http://www.newscom.com/cgi-bin/prnh/20000119/VERTEXLOGO

http://www.newscom.com/cgi-bin/prnh/20000502/BOGER AP Archive:

http://photoarchive.ap.org PRN Photo Desk, 888-776-6555 or

201-369-3467

Company News On Call: Company News On-Call:

http://www.prnewswire.com/comp/938395.html

[Guest guest]

Phase II, 24-Week Results for Vertex's Merimepodib Presented at the Annual

HEP DART Conference

VERTEX PHARMACEUTICALS JOSHUA BOGER

Dr. Boger, chairman and CEO, Vertex Pharmaceuticals Incorporated.

Press Contact: Michele Karpf Belansky, corporate communications,

617-444-6259.

CAMBRIDGE, MA USA 07/23/2002

CAMBRIDGE, Mass., Dec. 17 /PRNewswire-FirstCall/ -- An investigational

new

drug, merimepodib (VX-497), enhances the antiviral effect of pegylated-

interferon (peg-IFN) and ribavirin at 24 weeks of treatment in hepatitis C

virus (HCV) patients who were non-responsive to treatment with a previous

course of interferon-alfa and ribavirin, according to results presented at

the

HEP DART 2003 Frontiers in Drug Development for Therapies for Viral

Hepatitis

in Kauai, Hawaii. Merimepodib is an oral therapy for the treatment of HCV

being developed by Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX).

Vertex

retains worldwide commercial rights to merimepodib and is now planning to

initiate additional studies with merimepodib, including a first pivotal

study,

in hepatitis C patients in 2004.

The data from the core study period, presented at HEP DART, indicate

that

the triple combination of merimepodib, peg-IFN and ribavirin was well

tolerated and led to a statistically significant, dose-dependent increase in

the proportion of patients with undetectable levels of hepatitis C virus (<

50

IU/mL; approximately < 100 copies/mL) after 24 weeks of treatment. The

study

enrolled patients with genotype 1 HCV, which is the most common viral strain

and which is associated with the lowest response to combination therapy.

" Genotype 1 hepatitis C patients who are refractory to the combination

therapy of interferon and ribavirin represent a very difficult-to-treat

patient population and typically show limited, if any, viral response upon

re-

treatment, " stated Dr. Marcellin, Professor of Medicine at

University

of Paris VII, and the lead investigator for the study. " While the study was

designed primarily for an analysis of safety and tolerability, the

additional

antiviral activity observed with merimepodib at 24 weeks is encouraging. "

" Merimepodib represents a potentially important near-term treatment

advance in chronic hepatitis C as part of a combination therapy approach

that

may increase the ability of patients to achieve viral clearance, " stated

J. Alam, M.D., Senior Vice President of Drug Evaluation and Approval. " The

formal presentation of these Phase II, 24-week results affirms our

commitment

to rapidly advance the clinical development of merimepodib. These results

will help to guide the clinical path of merimepodib going forward in 2004. "

Study Design

The Phase II, double-blind, placebo-controlled, randomized study

reported

today was designed to evaluate the safety and tolerability of two dose

regimens of merimepodib (MMPD) in combination with peg-IFN and ribavirin in

patients with HCV genotype 1 who were non-responsive to interferon-alfa and

ribavirin therapy. Non-response was defined as at least 12 weeks of prior

treatment with documented, detectable HCV-RNA at the end of the treatment

period. The secondary objective of the study was to assess the

pharmacokinetics and clinical activity of merimepodib. The trial enrolled

31

patients who were treated with 25 mg MMPD, 50 mg MMPD, or placebo twice

daily

(BID) in combination with standard doses of peg-IFN and ribavirin for 24

weeks. Following the 24-week core study, patients who were HCV-RNA

undetectable continued on assigned treatment for an additional 24 weeks in

an

extension phase. Collection of 48-week end-of-treatment data and six-month

post-treatment sustained virologic response data is continuing.

Safety Results

Study results showed that merimepodib was well tolerated through 24

weeks

of treatment. Adverse events that appeared most closely associated with

merimepodib were diarrhea, abdominal pain, and mild rash, which occurred in

none of the patients in the placebo group and in 18% to 24% of patients in

the

merimepodib treatment groups. Injection site inflammation as a result of

peg-

IFN appeared to be less common in patients treated with merimepodib.

Additionally, merimepodib did not appear to exacerbate the incidence of

hematological toxicities associated with peg-IFN and ribavirin treatment.

Total bilirubin levels were similar across groups, suggesting there was no

increase in the incidence of hemolytic anemia that is associated with

ribavirin. The majority of adverse events reported were consistent with the

known side effect profile for peg-IFN and ribavirin treatment, and the

addition of merimepodib did not appear to increase the clinical severity of

these events.

Efficacy Results

Study results showed that, relative to placebo, merimepodib treatment

produced a statistically significant, dose-dependent increase in the

percentage of patients who achieved undetectable levels of HCV-RNA at 24

weeks. The three treatment groups had comparable levels of baseline

HCV-RNA.

At 24 weeks, 86% (6 of 7 patients) of patients receiving 50 mg MMPD BID had

undetectable levels of HCV-RNA, compared to 33% (2 of 6) of patients

receiving 25 mg MMPD BID and 33% (3 of 9) of patients receiving placebo (p =

0.03; Jonckheere-Terpstra test for increasing dose response among patients

on-

treatment at week 24). The on-treatment analysis of the percentage of

patients who were HCV-RNA undetectable at week 24 was the primary clinical

activity endpoint in the study. Analysis of all patients randomized

(intent-

to-treat population; ITT) also revealed a statistically significant, dose-

dependent antiviral effect. Seventy-three percent (8 of 11 patients)

receiving 50 mg MMPD BID achieved undetectable levels of HCV-RNA on at least

one occasion during the study, compared to 20% (2 of 10) of patients

receiving

25 mg MMPD BID and 30% (3 of 10) of the placebo group (p = 0.02; Jonckheere-

Terpstra test for increasing dose response). All patients received

pegylated-

interferon and ribavirin, on a weight-adjusted basis, in addition to the

randomized treatment.

Additionally, data suggested that, compared to baseline, patients

treated

with merimepodib showed a decline in alanine aminotransferase (ALT), a

marker

of liver inflammation. Baseline ALT levels were similar across all three

treatment groups. At 24 weeks, median ALT was lower among patients

receiving

50 mg MMPD BID (18.5 IU/L) than patients receiving 25 mg MMPD BID (41.0

IU/L)

or placebo (45.0 IU/L).

Clinical Need and Market Opportunity in HCV Infection

HCV infection is a serious disease that causes inflammation of the

liver,

which may lead to fibrosis and cirrhosis, liver cancer, and ultimately,

liver

failure. Chronic hepatitis C infection afflicts approximately 2.7 million

people in the U.S., many of whom are unaware of their infected status.

Current treatments provide a sustained viral response for only 40 to 50

percent of patients chronically infected with genotype 1 HCV, the most

difficult viral strain to treat and the most common form in the U.S.

Patients

who are non-responsive to current HCV therapy have limited treatment

options,

and clinical experience shows that only a very low proportion of such

patients

achieve a sustained viral response with subsequent treatment regimens. HCV

may go undetected for up to 20 years following initial infection.

Worldwide,

the disease strikes as many as 185 million people. Each year, 8,000 to

10,000

people in the U.S. die from complications of HCV.

Background on Merimepodib

Merimepodib is a small molecule, orally administered inhibitor of the

enzyme inosine monophosphate dehydrogenase (IMPDH). IMPDH inhibition may

represent an attractive strategy for increasing the sustained viral response

rate in HCV patients, the principal goal of treatment. IMPDH inhibition

leads

to a reduction in intracellular guanosine triphosphate (GTP), a cellular

molecule required by viruses for replication. Recent reports in the medical

literature suggest that IMPDH inhibitors such as merimepodib may enhance the

antiviral activity of ribavirin in vitro by depleting GTP and increasing the

rate of incorporation of ribavirin into viral RNA, rendering the virus

nonfunctional. The antiviral activity observed clinically when merimepodib

is

added to ribavirin-containing HCV therapies is consistent with these

preclinical findings.

About Vertex

Vertex Pharmaceuticals Incorporated is a global biotechnology company

committed to the discovery and development of breakthrough small molecule

drugs for serious diseases. The Company's strategy is to commercialize its

products both independently and in collaboration with major pharmaceutical

partners. Vertex's product pipeline is principally focused on viral

diseases,

inflammation, autoimmune diseases and cancer. Vertex co-promotes the new

HIV

protease inhibitor, Lexiva, with GlaxoKline.

This press release may contain forward-looking statements, including

statements that (i) merimepodib has the potential to increase the ability of

patients to achieve HCV viral clearance, based on 24-week clinical results;

(ii) merimepodib holds promise as part of combination therapy for HCV

patients

who have limited treatment options and represents an attractive commercial

opportunity for Vertex; and (iii) further clinical study of merimepodib will

be initiated in 2004. While management makes its best efforts to be

accurate

in making forward-looking statements, such statements are subject to risks

and

uncertainties that could cause Vertex's actual results to vary materially.

These risks and uncertainties include, among other things, the risks that

clinical trials for merimepodib may not proceed as planned due to technical,

scientific, or patient enrollment issues, that final results from clinical

trials with merimepodib will not reflect positive interim results and other

risks listed under Risk Factors in Vertex's form 10-K filed with the

Securities and Exchange Commission on March 31, 2003.

Lexiva is a registered trademark of the GlaxoKline group of

companies.

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

Vertex Contacts:

Partridge, Director, Corporate Communications (617) 444-6108

Jaren Irene Madden, Media Relations Specialist, Corporate

Communications

(617) 444-6750

SOURCE Vertex Pharmaceuticals Incorporated

Web Site: http://www.vrtx.com

Photo Notes: NewsCom:

http://www.newscom.com/cgi-bin/prnh/20000119/VERTEXLOGO

http://www.newscom.com/cgi-bin/prnh/20000502/BOGER AP Archive:

http://photoarchive.ap.org PRN Photo Desk, 888-776-6555 or

201-369-3467

Company News On Call: Company News On-Call:

http://www.prnewswire.com/comp/938395.html