Press Release

Cambridge, MA, December 5, 2005 - Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced today the initiation of a Phase II clinical trial for VX-950, an investigational oral hepatitis C virus (HCV) protease inhibitor for the treatment of HCV infection. The 28-day study will evaluate the safety, tolerability and pharmacodynamics of VX-950 when combined with pegylated interferon and ribavirin. Pegylated interferon and ribavirin are two approved treatments for HCV infection. Twelve treatment-naive subjects will be enrolled in the study at two centers in the United States. This is the first clinical study of VX-950 to be initiated under an open investigational new drug (IND) application with the United States Food and Drug Administration, and marks the beginning of a broad Phase II clinical development program planned for VX-950 that will evaluate the compound in multiple clinical studies in 2006, including a three-month study in more than 200 treatment-naive patients.

"This first Phase II study for VX-950 will enable Vertex to evaluate the safety, tolerability and pharmacodynamics of VX-950 over 28 days when combined with pegylated interferon and ribavirin," said John Alam, M.D., Senior Vice President of Drug Evaluation and Approval at Vertex. "This initial Phase II trial is anticipated to support the evaluation of VX-950 in a key three-month Phase II study in more than 200 HCV patients that we expect to initiate in early 2006."

Phase II Development Plans
The objectives of the 28-day Phase II study announced today are to evaluate the safety, tolerability and pharmacodynamics of VX-950 dosed at 750 mg every eight hours with standard doses of pegylated interferon and ribavirin. Vertex expects to obtain 28-day results from this initial Phase II study in the first quarter of 2006. Following completion of 28 days of treatment, patients will receive the standard of care. In early 2006, Vertex expects to initiate a three-month Phase II clinical study in more than 200 treatment-naive subjects. A major objective of this three-month study, in addition to an evaluation of safety, will be to measure HCV RNA at the end of treatment and post-treatment as a measure for sustained viral response, potentially enabling a decision to move to Phase III clinical development of VX-950. Vertex also plans to initiate multiple other clinical studies throughout 2006.

Vertex recently completed a healthy volunteer study with the new VX-950 tablet formulation. Results from this study support the use of the VX-950 tablet formulation in Phase II studies.

About Hepatitis C
Hepatitis C is a liver disease caused by the hepatitis C virus, which is found in the blood of people with the disease. HCV, a serious public health concern affecting 3.4 million individuals in the United States, is spread through direct contact with the blood of infected people. Though many people with hepatitis C may not experience symptoms, others may have symptoms such as jaundice, abdominal pain, fatigue and fever. Hepatitis C significantly increases a person's risk for developing long-term infection, chronic liver disease, cirrhosis or death.

About VX-950
VX-950 is an oral inhibitor of hepatitis C virus protease, an enzyme essential for viral replication. In a 14-day, Phase Ib study concluded earlier in 2005, VX-950, administered as a single agent, produced a rapid and dramatic reduction in HCV RNA in HCV patients. In the Phase Ib study, 26 of 28 patients receiving any dose of VX-950 achieved more than a 3-log10 reduction in plasma HCV RNA within two days of treatment. After 14 days, patients in the best dose group (750 mg every 8 hours) achieved a mean reduction in HCV RNA of 4.4-log10, a 25,000-fold reduction in viral levels. Overall in the Phase Ib study, adverse events observed in patients receiving VX-950 that were considered possibly related to the drug were mild, and generally similar in frequency to events in the placebo group. The most common adverse events reported in both placebo and VX-950 patients were headache, frequent urination and gastrointestinal symptoms.

Vertex researchers were the first to solve the three-dimensional crystal structure of HCV protease, and have used structural insights to enable the design of small molecule HCV protease inhibitors, including VX-950.

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 companies. Vertex's product pipeline is principally focused on viral diseases, inflammation, autoimmune diseases and cancer. Vertex co-promotes the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.

Lexiva is a registered trademark of the GlaxoSmithKline group of companies.

Safe Harbor Statement
This press release may contain forward-looking statements, including statements that (i) results from an initial Phase II study will be available in the first quarter of 2006; (ii) a three-month Phase II study in more than 200 patients will be initiated in early 2006, and will potentially enable a decision to move into phase III evaluation of VX-950; and (iii) VX-950 will be evaluated in multiple additional clinical studies in 2006. 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 VX-950 may not proceed as planned due to technical, scientific, or patient enrollment issues, or disagreements with regulatory authorities over trial design or other matters, that the scale and scope of future clinical and nonclinical studies may change and will be determined in significant part by data collected in ongoing and future trials, that further clinical studies of VX-950 may not reflect the results obtained in early clinical and nonclinical studies, that ongoing nonclinical studies, including toxicology studies, will yield currently unanticipated negative outcomes, that results from the Company's clinical trials commenced during 2006 will be insufficient to support a Phase III program without additional trials and consequent delay in the timetable for potential approval, and other risks listed under Risk Factors in Vertex's form 10-K filed with the Securities and Exchange Commission on March 16, 2005.

Vertex Contacts:
Lynne Brum, VP, Corporate Communications and Financial Planning, (617) 444-6614
Michael Partridge, Director, Corporate Communications, (617) 444-6108
Lora Pike, Manager, Investor Relations, (617) 444-6755
Zachry Barber, Specialist, Media Relations, (617) 444-6470