A Phase 2/3 Open-label Extension Study to Evaluate Long-Term Safety and Efficacy With VX-509 in Subjects With Rheumatoid Arthritis

VX-509 is an oral, selective Janus kinase 3 (JAK3) inhibitor being developed by Vertex. In
autoimmune diseases, JAK3 is an essential component of the immune signaling cascade. This
cascade ultimately contributes to abnormal immune response that results in chronic
inflammation and, in the case of rheumatoid arthritis (RA), irreversible damage to cartilage
and bones. Selective inhibition of JAK3 offers a new disease modifying approach to the
treatment of RA.

This study will follow a "treat to target" (T2T) paradigm. T2T strategies have been followed
in non-rheumatologic fields for decades. T2T trials have been conducted for RA from the late
1990's, and have substantiated the concept that treating to a target is associated with a
better outcome than standard of care treatment. This has led to recommendations by experts
to use T2T strategies in clinical practice.

Inclusion Criteria:

- Subjects must have completed the assigned study drug treatment phase of a previous
VX-509 study (e.g., Study 103).

- Subjects must voluntarily sign and date the Study 104 informed consent document.

- Subject must be willing and able to comply with the scheduled visits, treatment plan,
laboratory tests, contraceptive guidelines, and other study procedures.

Exclusion Criteria:

- Inflammatory and rheumatological disorders other than RA, where arthritis may be a
prominent feature.

- History of any clinically significant illness that might, in the opinion of the
investigator, confound the results of the study or pose an additional risk in
administering study drug(s) to the subject

- History of tuberculosis (TB), regardless of history of antimycobacterial treatment.

- Planned surgery during the study.

- History of alcohol or drug abuse, or excessive alcohol consumption as determined by
the investigator, during the previous 12 months before Day 1.

- Pregnant or nursing an infant or with a life partner who is pregnant, nursing, or
planning to become pregnant