UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

SCHEDULE 13G

Under the Securities Exchange Act of 1934

(Amendment No. 1)*

ALEXZA PHARMACEUTICALS, INC.

(Name of Issuer)

Common Stock, $0.0001 par value

(Title of Class of Securities)

015384100

(CUSIP Number)

December 31, 2012

(Date of Event which Requires Filing of this Statement)

Check the appropriate box to designate the rule pursuant to which this Schedule if filed:

¨ Rule 13d-1(b)

xRule 13d-1(c)

¨ Rule 13d-1(d)

This Amendment No. 1 to Schedule 13G (“Amendment No. 1”) amends and supplements the statement on Schedule 13G initially filed on February 27, 2012 (the “Original Filing”). Information reported in the Original Filing remains in effect except to the extent that it is expressly amended, restated or superseded by information contained in this Amendment No. 1. Capitalized terms used and not defined in this Amendment No. 1 have the meanings set forth in the Original Filing. This Amendment No. 1 is being filed jointly pursuant to Rule 13d-1(k)(1) under the Securities Exchange Act of 1934, as amended (the “Exchange Act”) by the Reporting Persons.

As of December 31, 2012 (unless otherwise indicated):

Boxer Capital, Boxer Management and Joseph Lewis beneficially own 806,714* Common Shares, which includes 357,709 Common Shares and 449,005 Warrants to purchase Common Shares, which may only be converted to the extent that, after such conversion, the Reporting Persons would beneficially own no more than 4.999% of the outstanding Common Shares (the “Ownership Limitation”). MVA beneficially owns 253,681* Common Shares, including 24,052 Common Shares and 229,629 Warrants to purchase Common Shares, which are subject to the Ownership Limitation. Aaron Davis no longer beneficially owns any Common Shares.

The Common Shares beneficially owned by Boxer Capital, Boxer Management and Joseph Lewis represent 4.999%* of the Issuer’s outstanding Common Shares outstanding. The Common Shares beneficially owned by MVA represent 1.6%* of the Issuer’s outstanding Common Shares. The Common Shares beneficially owned by Aaron Davis represent 0.0%* of the Issuer’s outstanding Common Shares.

As of the date hereof, MVA has the sole power to vote the 253,681* Common Shares it beneficially owns. Boxer Capital, Boxer Management and Joseph Lewis do not have the sole power to vote or direct the vote of any Common Shares, including with regard to the Common Shares held by MVA.

Boxer Capital, Boxer Management and Joseph Lewis have shared voting power with respect to the 806,714* Common Shares they beneficially own. As of the date hereof, Boxer Capital, Boxer Management and Joseph Lewis do not beneficially own any Common Shares. Neither MVA nor Aaron Davis has shared power to vote or direct the vote of any Common Shares.

MVA has the sole power to dispose of the 253,681* Common Shares it beneficially owns. Boxer Capital, Boxer Management and Joseph Lewis do not have the sole power to dispose or direct the disposition of any Common Shares, including with regard to the Common Shares held by MVA.

The Boxer Capital, Boxer Management and Joseph Lewis have shared dispositive power with respect to any Common Shares they beneficially own. Boxer Capital, Boxer Management and Joseph Lewis beneficially own 806,714* Common Shares, consisting of 357,709 Common Shares and 449,005 Warrants to purchase Common Shares, which are subject to the Ownership Limitation. Neither MVA nor Aaron Davis has shared power to dispose of or direct the disposition of any Common Shares.

In accordance with Rule 13d-4 under the Securities Exchange Act of 1934, as amended, because the number of shares of Common Stock into which the Warrants are exercisable is limited, pursuant to the terms of such instrument, to the Ownership Limitation, the Reporting Persons disclaim beneficial ownership of any and all shares of Common Stock that would cause any Reporting Person’s beneficial ownership to exceed the Ownership Limitation.

If this statement is being filed to report the fact that as of the date hereof the Reporting Persons have ceased to be the beneficial owner of more than 5 percent of the class of securities, check the following [X].

Only Boxer Capital has the right to receive dividends and the proceeds from the sale of the Common Shares held by Boxer Capital. Only MVA has the right to receive dividends and the proceeds from sale of the Common Shares held by the MVA. See Item 4 above.

(c) By signing below I certify that, to the best of my knowledge and belief, the securities referred to above were not acquired and are not held for the purpose or with the effect of changing or influencing the control of the issuer of the securities and were not acquired and are not held in connection with or as a participant in any transaction having that purpose or effect.

Exhibits

SIGNATURE

After reasonable inquiry and to the best of my knowledge and belief, I certify that the information set forth in this statement is true, complete and correct.

Exhibit 1

JOINT FILING AGREEMENT

The undersigned hereby agree that the Statement on Schedule 13G, dated February 27, 2012, with respect to the shares of Alexza Pharmaceuticals, Inc. Common Stock, par value $0.0001 per share, is, and any amendments thereto executed by each of us shall be, filed on behalf of each of us pursuant to and in accordance with the provisions of Rule 13d-1(k)(1) under the Securities Exchange Act of 1934, as amended, and that this Agreement shall be included as an Exhibit to the Schedule 13G and each such amendment. Each of the undersigned agrees to be responsible for the timely filing of the Schedule 13G and any amendments thereto, and for the completeness and accuracy of the information concerning itself contained therein. This Agreement may be executed in any number of counterparts, all of which taken together shall constitute one and the same instrument.

IN WITNESS WHEREOF, the undersigned have executed this Agreement as of the 27th day of February, 2012.