Exhibit 10.2

OREXIGEN THERAPEUTICS, INC.

AMENDMENT NO. 1 TO AMENDED AND RESTATED EMPLOYMENT AGREEMENT

JUNE     , 2011

Reference is made to the AMENDED AND RESTATED EMPLOYMENT AGREEMENT (the “Agreement”) dated February 22, 2010 by and between OREXIGEN THERAPEUTICS, INC. (“Orexigen” or the “Company”) with its principal place of business located at 3344 N. Torrey Pines Ct., Suite 200, La Jolla, CA 92037 and MARK BOOTH (“Executive”). All capitalized terms used herein and not otherwise defined shall have the meanings assigned to such terms in the Agreement.

WHEREAS, the parties desire to amend certain terms of the Agreement in accordance with the terms hereof (this “Amendment”).

NOW THEREFORE, for good and valuable consideration, the receipt and sufficiency of which is hereby acknowledged by the parties, the parties hereto, intending to be legally bound, agree as follows:

“Position and Duties. Subject to terms set forth herein, the Company agrees to continue to employ Executive, on a Part-Time Basis (as defined below), in the position of Chief Commercial Officer and Executive hereby accepts such continued employment. Executive shall perform such duties as are customarily associated with the position of Chief Commercial Officer, on a Part-Time Basis, and such other duties as are assigned to Executive by the Chief Executive Officer and/or President of the Company. Subject to the terms of this Agreement, the Company may change Executive’s duties, responsibilities, title, and reporting relationship at its discretion. Effective June 16, 2011 through December 16, 2011 (the “Term”), during the term of Executive’s employment with the Company, Executive will devote Executive’s best efforts and one (1) day (equal to an eight (8) hour day) per week to the business of the Company (“Part-Time Basis”). Notwithstanding the foregoing, it is agreed and understood that Executive shall be allowed to participate on the boards of directors of two companies and Executive may serve on other boards of directors and provide other consulting and/or business services for other companies during the Term with prior written notice thereof given to the Chief Executive Officer. Executive shall not be required to relocate his principal residence from Lake Forest, Illinois.”

“Base Salary. Executive shall receive for services to be rendered hereunder an annual base salary of $74,000.00 (“Amended Base Annual Salary”), less required deductions and withholdings, payable on the regular payroll dates of the Company.”

“Annual Bonus. In addition to the Amended Base Annual Salary, during each calendar year Executive will be eligible for an annual performance bonus, equal to up to 50% of the Amended Base Annual Salary, and which is 100% based upon the achievement of Executive’s performance goals and objectives (“Amended Annual Bonus”). The Compensation Committee of the Company’s Board shall determine in its sole discretion whether any such bonus has been earned and, if so, the amount of any such bonus. Executive must be an employee in good standing at the time the Compensation Committee decides to award the Amended Annual Bonus and, if Executive leaves the Company at any time and for any reason prior to such date, he will not be eligible to receive such a bonus or any pro-rata portion of such bonus. Such Amended Annual Bonus shall be evaluated and paid no later than December 31 of the calendar year following the calendar year to which such Amended Annual Bonus relates.”

“Vacation and Paid Time Off. Executive shall be entitled to 4 business days of paid vacation each year, accruing on a monthly basis, and 8 paid holidays each year.”

“Cash Severance. The Company shall make a single lump sum severance payment to Executive in an amount equal to $370,000, less required tax withholdings and deductions (the “Severance Payment”). The Severance Payment will be paid within sixty (60) days after the Termination Date, but in no event later than March 15 of the year following the year of termination.”

“Cash Severance. The Company shall make a single lump sum severance payment to Executive in an amount equal to $370,000, multiplied by one point five (1.5), less required tax withholdings and deductions (the “Change in Control Payment”). The Change in Control Payment will be paid within sixty (60) days after the Termination Date, but in no event later than March 15 of the year following the year of termination.”

“Other Compensation and Benefits. If: (i) the Company terminates Executive’s employment for Cause or as a result of his death or disability, or (ii) if Executive resigns his employment at any time, except as a result of a Constructive Termination during the Change in Control Period, then this Agreement shall automatically terminate (except for Article V and Article VII, which shall continue in effect), and upon such termination, the Company shall have no further obligation to Executive, his spouse or estate, except that the Company shall pay to Executive the amount of his Amended Base Annual Salary, and unused vacation pay, accrued to the date of such termination.”

[Signature Page to Follow]

IN WITNESS WHEREOF, the parties hereto have duly executed this Amendment as of the date set forth above.

[Signature Page to Amendment No. 1 to M. Booth Employment Agreement]