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corresp

March 10, 2011

By EDGAR Transmission

Securities and Exchange Commission

Division of Corporate Finance

100 F Street, N.E.

Washington, D.C. 20549

Attention: Johnny Gharib

    Re:

    Alnylam Pharmaceuticals, Inc.

    Form 10-K

    Filed February 26, 2010

    File No. 000-50743

    Ladies and Gentlemen:

On behalf of Alnylam Pharmaceuticals, Inc. (the “Company”), I am writing in response to comments
contained in the letter dated February 28, 2011 (the “Letter”) from Jeffrey Riedler of the Staff
(the “Staff”) of the Securities and Exchange Commission (the “Commission”) to John M. Maraganore,
the Company’s Chief Executive Officer. The responses set forth below are keyed to the numbering of
the comments and the headings used in the Letter.

Proxy Statement on Schedule 14A, filed April 20, 2010

2009 Annual Incentive Program, page 26

    1.

    We note your response to our prior comment 4 and your disclosure that the company has not
disclosed Ms. Allen’s performance target with respect to specified internal operating expense
levels under its annual operating plan because the company believes that this information
constitutes confidential financial data, the disclosure of which would result in competitive
harm to it. However, you have already disclosed your operating expenses in your 2010 10-K
filed on February 18, 2011. Please revise your disclosure to include a discussion of Ms.
Allen’s performance target with respect to specified internal operating expense levels and
compare them to the level of operating expenses incurred by the company.

    Response:

    In response to the Staff’s comment, the Company has revised the disclosure
regarding Ms. Allen’s individual objectives to include a discussion of Ms. Allen’s
performance target with respect to specified internal operating expense levels. The
Company notes that it has not provided a comparison of this performance target to the
level of GAAP operating expenses disclosed in the Company’s Annual Report on Form 10-K
for the year ended December 31, 2010, as these measures are not the same. As
previously noted by the Company, multiple factors go into determining the Company’s
operating plan,

Securities and Exchange Commission

March 10, 2011

Page 2

    which contains financial targets and budgets that are used to guide the
operations of the Company. The Company has included in its revised
disclosure below an explanation of the distinction between its internal
operating expense levels under its annual operating plan and its reported
GAAP operating expenses for 2010. The Company intends to include revised
disclosure regarding Ms. Allen’s individual objectives and performance in its
2011 proxy statement substantially similar to that set forth below:

“Ms. Allen’s individual objectives were focused on meeting specified financial goals, including
meeting internal operating expense levels of no more than $110 million under our annual operating
plan, and year-end minimum cash balance requirements of greater than $340 million (excluding a
potential one-time license payment from a collaborator) ([ ]%), supporting business development
efforts to establish strategic alliances to fund our business ([ ]%), managing our investment
portfolio ([ ]%) and managing the audit of our financial statements, along with various public
reporting obligations and tax matters ([ ]%), and achieving specified metrics with respect to the
information technology and facilities groups ([ ]%). Ms. Allen’s goals relating to internal
operating expense levels were based upon our annual operating plan. Multiple factors go into
determining our operating plan, which contains financial targets and budgets that we use to guide
our operations. Internal operating expenses do not align with reported GAAP operating expenses, as
they consist primarily of cash operating expenses and exclude items such as depreciation and
stock-based compensation. Our compensation committee also considered both Dr. Maraganore’s and Mr.
Greene’s recommendations with respect to Ms. Allen’s performance. Our compensation committee
determined that Ms. Allen achieved [ ]% of her individual objectives for 2010, including meeting
year-end internal operating expense levels of no more than $110 million under our annual operating
plan and achievement of internal year-end cash balance objectives of greater than $340 million,
ending 2010 with $350 million. Our compensation committee determined that under the 2010 annual
incentive program, Ms. Allen earned a cash incentive award of $[ ], representing [ ]% of her
target cash award opportunity, reduced by the corporate performance modifier of [ ]%.”

If you require additional information, please telephone either the undersigned at (617) 551-8200,
or Lia Der Marderosian of WilmerHale, the Company’s outside counsel, at (617) 526-6000.

Very truly yours,

/s/ Michael P. Mason

Michael P. Mason

Vice President, Finance and Treasurer

    cc:

    Philip T. Chase, Esq.

    Lia Der Marderosian, Esq.