Exhibit 10.10



                                                 November 8, 2004


Vicki L. Sato
43 Larch Road
Cambridge, MA 02138

Re:  Second Amendment to Employment Agreement

Dear Vicki,

         The Employment Agreement dated as of November 1, 1994, as amended by
letter agreement dated May 12, 1995, between you and Vertex Pharmaceuticals
Incorporated (the "Agreement") hereby is amended, effective November 8, 2004, as
follows:

         1.   Section 6.4 shall be deleted in its entirety, and the following
              substituted therefor:

              6.4  TERMINATION WITHOUT CAUSE. If the Executive's employment is
                   terminated by the Company without Cause, the Executive shall
                   be entitled to 18 months of Severance Pay. "Severance Pay"
                   shall mean an amount equal to the Executive's base salary
                   then in effect, plus the amount of the target bonus for the
                   year in which the Executive's employment is terminated
                   divided by twelve (12) (each of the 12 shares to constitute
                   a "month's" Severance Pay). In addition: (i) all
                   unexercisable stock options held by the Executive as of the
                   date of termination shall be deemed to have been held by the
                   Executive for an additional eighteen (18) months after the
                   date of termination, for purposes of vesting and exercise
                   rights, and any unexercisable stock options that become
                   exercisable as a result thereof shall remain exercisable
                   until the earlier of (1) the end of the 90-day period
                   following the date of termination and (2) the date the
                   option would otherwise expire and (ii) the Company's lapsing
                   repurchase right with respect to shares of restricted stock
                   held by the Executive shall lapse with respect to the
                   Pro-Rata Share of Restricted Stock. The "Pro-Rata Share of
                   Restricted Stock" shall mean, for any grant of restricted
                   stock as to which the Company's repurchase right lapses
                   ratably over a specified period (e.g. in equal annual
                   increments over four years), that number of shares as to
                   which the Company's repurchase right with respect to those
                   shares would have lapsed if the Executive's employment by
                   the Company had continued an additional eighteen month
                   period. For any other shares of restricted stock, "Pro-Rata
                   Share of Restricted Stock" shall mean, as to any shares of
                   restricted stock which were granted on the same date and as
                   to which the Company's repurchase right lapses on the same
                   date, that portion of such shares calculated by multiplying
                   the number of shares by a fraction, the numerator of which
                   is the number of days that have passed since the date of
                   grant, plus the number of days in 18 months, and the
                   denominator of which is




Vicki L. Sato
November 8, 2004
Page 2


                    the total number of days from the date of the grant until
                    the date (without regard to any provisions for earlier
                    vesting upon achievement of a specified goal) on which the
                    Company's repurchase right would lapse under the terms of
                    the grant. Notwithstanding the foregoing, the terms of any
                    option agreement or restricted stock agreement shall govern
                    the acceleration of vesting or lapsing of the Company's
                    repurchase rights, as applicable, except to the extent that
                    the terms of this Employment Agreement are more favorable to
                    the Executive.

          2.  Appendix A, Section 1.3(i)(a) shall be deleted in its entirety,
              and the following substituted therefor:

              (a) substantial adverse alteration in the nature or status of the
              Executive's position or responsibilities as President of the
              Company or the condition of her employment as President of the
              Company;

          As so amended, the Agreement shall remain in full force and effect.

          If you agree to the foregoing amendment, please so indicate by signing
and returning the enclosed copy of this letter.


                                         VERTEX PHARMACEUTICALS INCORPORATED


                                         By: /s/ Joshua S. Boger
                                             ---------------------------------
                                             Joshua S. Boger, Chairman and CEO


Accepted and Agreed:

/s/ Vicki L. Sato
- ------------------------
Vicki L. Sato