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                                                                   EXHIBIT 10.46


                       FIRST AMENDMENT TO LEASE AGREEMENT

This First Amendment to Lease Agreement (the "Amendment") is made and entered
into as of December 1, 2000, by and between LINCOLN-RECP EMPIRE OPCO, LLC, a
California limited liability company ("Landlord") and AVIGEN, INC., a Delaware
corporation ("Tenant"), with reference to the following facts.

                                    RECITALS

A.      Landlord and Tenant have entered into that certain Lease Agreement dated
        as of November 2, 2000 (the "Lease") for the leasing of certain premises
        consisting of approximately 67,482 rentable square feet located at 1301
        Harbor Bay Parkway, Alameda, California (the "Premises") as such
        Premises are more fully described in the Lease, for a term commencing on
        December 1, 2000, and expiring on November 30, 2010.

B.      Pursuant to Article 2 of the Lease, the Premises on the second floor of
        the Building comprising approximately 32,945 rentable square feet (the
        "Remaining Premises") was anticipated to be delivered to Tenant on or
        about October 1, 2001 (the "RP Commencement Date").

C.      Tenant now wishes to, effective as of December 1, 2000, occupy
        approximately 22,945 rentable square feet of the Remaining Premises (the
        "A Remaining Premises"), rather than waiting until the RP Commencement
        Date to occupy any of the Remaining Premises, and wishes to occupy the
        entire Remaining Premises as of March 1, 2001, rather than the RP
        Commencement Date, and Landlord is agreeable to the same.

D.      Phoenix American, Inc., a California corporation, successor in interest
        to Resource/Phoenix, Inc. ("Phoenix") currently occupies the balance of
        the Remaining Premises (the "B Remaining Premises") comprising
        approximately 10,000 rentable square feet pursuant to a lease from
        Landlord.

E.      Landlord and Tenant now wish to amend the Lease upon and subject to each
        of the terms, conditions and provisions set forth herein.

NOW, THEREFORE, in consideration of the foregoing and for other good and
valuable consideration, the receipt and adequacy of which are hereby
acknowledged, Landlord and Tenant agree as follows:

        1. RECITALS: Landlord and Tenant agree that the above recitals are true
and correct and are hereby incorporated herein as though set forth in full.

        2. MODIFICATIONS TO LEASE: Effective as of December 1, 2000 (the
"Effective Date"), the Lease is hereby modified as follows:

                2.1 PREMISES. ARTICLE 2 - LEASE TERM of the Lease is hereby
        amended such that the fifth (5th) and sixth (6th) sentences thereof
        shall read as follows:

                      "Landlord has delivered, and Tenant acknowledges having
               possession of, approximately 34,537 rentable square feet of the
               Premises on the ground floor of the Building (the "Initial
               Premises") to Tenant on or about the Lease Commencement Date; and
               Landlord anticipates delivering the balance of the Premises on
               the second floor of the Building comprising approximately 32,945
               rentable square feet (the "Remaining Premises"), approximately
               22,945 rentable square feet (the "A Remaining Premises"), as
               shown on Exhibit A to this Amendment, is anticipated to be
               delivered to Tenant on or about December 1, 2000 (the "RPA
               Commencement Date"); and approximately 10,000 rentable square
               feet (the "B Remaining Premises"), as shown on Exhibit A to this
               Amendment, is anticipated to be delivered to Tenant on or about
               March 1, 2001 (the "RPB Commencement Date"). If Landlord, for any
               reason, cannot deliver possession of the A Remaining Premises to
               Tenant on the RPA Commencement Date (in the condition that exists
               on the day after the Existing Tenant vacates the A Remaining
               Premises), or cannot deliver possession of the B Remaining
               Premises to Tenant on the RPB Commencement Date (in the condition
               that exists on the day after the Existing Tenant vacates the B
               Remaining Premises), in either case without any improvements,
               alterations, repairs, refurbishment or other modifications being
               made thereto (except as may be necessary to satisfy the
               requirements of Section 1.2 above), Landlord shall not be subject
               to any liability nor shall the validity of this Lease be
               affected; provided that the RPA Commencement Date and/or the RPB
               Commencement Date, as appropriate, shall be extended
               commensurately by the period of time Landlord is delayed in so
               delivering possession of the A Remaining Premises and/or the B
               Remaining Premises to Tenant without any improvements,
               alterations, repairs, refurbishment or other modifications being
               made thereto. Tenant's rights to use the A Remaining Premises and
               the B Remaining Premises shall be subject and subordinate to the
               rights of Phoenix; and no use by Tenant may unreasonably
               interfere with the rights of Phoenix to use and occupancy of
               Phoenix's premises."

                Throughout the Lease, references to the "RP Commencement Date"
        shall be deemed to be references to the "RPA Commencement Date" and/or
        the "RPB Commencement Date", as appropriate.

               2.2    RENT.

                      ARTICLE 3 - BASE RENT of the Lease is hereby amended as
               follows:

                       Base Rent for the A Remaining Premises is waived by the
               Landlord for the period from the RPA Commencement Date through
               the RPB Commencement Date. From and after the RPB Commencement
               Date, Tenant shall pay to Landlord Base Rent for both the RPA
               Remaining Premises and the RPB Remaining Premises at the monthly
               rate of $1.52 per rentable square


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               foot, or Fifty Thousand Seventy-six Dollars and Forty Cents
               ($50,076.40), through May 31, 2002; and thereafter Tenant shall
               pay to Landlord Base Rent for both the RPA Remaining Premises and
               the RPB Remaining Premises at the monthly rate of $1.59 per
               rentable square foot, or Fifty-two Thousand Three Hundred
               Eighty-two Dollars and Fifty-five Cents ($52,382.55).

               The second table set forth in Section 8. Base Rent (Article 3) of
        the Summary of Basic Lease Information in the Lease (for Base Rent for
        the "Remaining Premises" from the "RP Commencement Date" through
        December 31, 2002), is hereby revised in accordance with the following
        schedule:

<TABLE>
<CAPTION>
              --------------------- ------------------ ------------------------- --------------
                      TERM              REMAINING        REMAINING PREMISES -       MONTHLY
                                     PREMISES SQUARE    ANNUAL RENTAL RATE PER    INSTALLMENT
                                          FEET           RENTABLE SQUARE FOOT    OF BASE RENT
              --------------------- ------------------ ------------------------- --------------
              <S>                   <C>                <C>                       <C>
                3/1/01 - 5/31/02         32,945                 $18.24            $50,076.40
              --------------------- ------------------ ------------------------- --------------
               6/1/02 - 12/31/02         32,945                 $19.08            $52,382.55
              --------------------- ------------------ ------------------------- --------------
</TABLE>

               2.3    LETTER OF CREDIT.

                      Paragraph 20.2 LETTER OF CREDIT of the Lease is hereby
               amended as follows:

                      Upon the RPB Commencement Date, the face amount of the
               Letter of Credit shall be increased to be Two Million Dollars
               ($2,000,000.00).

        3. EFFECT OF AMENDMENT: Except as modified herein, the terms and
conditions of the Lease shall remain unmodified and continue in full force and
effect. In the event of any conflict between the terms and conditions of the
Lease and this Amendment, the terms and conditions of this Amendment shall
prevail. Tenant hereby renews its obligations to Landlord for the full, prompt
and timely payment of all rents and other sums required to be paid by Tenant
during the term of the Lease as herein modified, and for the full, prompt and
timely performance of, compliance with and observation of all the terms
contained in the Lease as herein modified.

        4. DEFINITIONS: Unless otherwise defined in this Amendment, all terms
not defined in this Amendment shall have the meaning set forth in the Lease.

        5. NO BROKER: Each party warrants and represents to the other that no
real estate broker, sales person, finder or other person has the right to
payment of a commission or fee in connection with this Amendment as a
consequence of contacts with such party. Each party shall indemnify, protect,
defend and hold the other harmless from any and all loss, cost, damage or
expense (including attorneys' fees and costs, including fees and costs on
appeal, if any) arising out of or related to claims for a real estate brokerage
commission, finder's fee or similar compensation, based upon allegations by the
claimant that it is entitled to a commission, fee or other compensation from the
indemnified party as a consequence of contacts with the indemnifying party.

        6. ENTIRE AGREEMENT: The Lease and this Amendment constitute the entire
understanding between the parties with respect to the Premises. No subsequent
amendment will be effective unless it is in writing and executed by the parties.

        7. COUNTERPARTS: This Amendment may be executed in counterparts, each of
which when executed and delivered shall be an original.

        8. AUTHORITY: Subject to the provisions of the Lease, this Amendment
shall be binding upon and inure to the benefit of the parties hereto, their
respective heirs, legal representatives, successors and assigns. Each party
hereto and the persons signing below warrant that the person signing below on
such party's behalf is authorized to do so and to bind such party to the terms
of this Amendment.


IN WITNESS WHEREOF, the parties have executed this Amendment as of the date and
year first above written.

                                            TENANT:

                                            AVIGEN, INC.,
                                            a Delaware corporation



Date:  12/13/00                             By: /s/ JOHN MONAHAN
     ------------------------------            ---------------------------------
                                            Name:   John Monahan
                                                 -------------------------------
                                            Title:  CEO
                                                  ------------------------------


Date:                                       By: /s/ THOMAS J. PAULSON
     ------------------------------            ---------------------------------
                                            Name:   Thomas J. Paulson
                                                 -------------------------------
                                            Title:  VP-Finance, CFO
                                                  ------------------------------


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                                     LANDLORD:

                                     LINCOLN-RECP EMPIRE OPCO, LLC,
                                     a California limited liability company

                                     By:    Legacy Partners Commercial, Inc.,
                                     as agent for LINCOLN-RECP EMPIRE OPCO, LLC,



Date:                                By: /s/ ROBERT F. PHIPPS
     ------------------------           ----------------------------------------
                                     Name:   Robert F. Phipps
                                          --------------------------------------
                                     Title:  Senior Vice President
                                           -------------------------------------




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