EX-10.42.4



 







    Exhibit 10.42.4



    [DURECT
    LETTERHEAD]



 




    January 20,
    2006



 



    BY FACSIMILE AND EXPRESS MAIL
CONFIDENTIAL



 



Peter A. Lankau

President and CEO

Endo Pharmaceuticals Inc.

100 Endo Boulevard

Chadds Ford PA 19317



 




	 	Re:	 	Amendment 3 to Development,
    Commercialization and Supply License Agreement





 



    Dear Peter:



 



    Reference is made to the Development, Commercialization and
    Supply License Agreement between Endo Pharmaceuticals Inc.
    (“Endo”) and DURECT Corporation (“DURECT”)
    effective November 8, 2002, as last amended
    November 22, 2004 (the “Agreement”). Effective on
    the date written above, Endo and DURECT hereby agree to amend
    the Agreement as follows:



 




	 	1.	 	Amendment to Section 4.6(a). Section 4.6(a) of the
Agreement shall be amended to replace each instance of “January
1, 2006” with “May 1, 2007”.






 






	 	2.	 	Amendment to Section 4.6(c). Section 4.6(c) of
    the Agreement shall be replaced in its entirety to read as
    follows:







 






	 	 	 	Notwithstanding anything to the contrary in Sections 4.6(a)
    and (b) and except as set forth in this
    Section 4.6(c), Endo shall have no obligations under
    Sections 4.6(a) and (b) to make any payments to DURECT
    for any Developments Costs incurred up to and including the date
    sixty (60) days following the delivery to Endo of written
    notice that a human pharmacokinetic trial has been completed
    with the Product together with a full study report of the
    results of such trial (such date, the “Trial Results Review
    Date”, such notice, the “Trial Completion Notice”
    and such trial, the “First Trial”). Notwithstanding
    the foregoing, in the event Endo has not delivered notice of its
    intent to terminate this Agreement pursuant to
    Section 13.3(e), then Endo shall be responsible for such
    portion of the Development Costs incurred after May 1, 2007
    in accordance with Section 4.6(a). Furthermore, until the
    Trial Results Review Date, DURECT hereby agrees to initiate any
    human trial only if such trial and the initiation thereof is
    consistent with a reasonable pharmaceutical company’s
    overall global strategic development plan for a product
    similarly situated to the Product. Finally, in no event shall
    Endo be liable for any costs associated with any human
    pharmacokinetic (PK) study undertaken by DURECT prior to the
    earlier of the Trial Results Review Date or March 31,
    2007.”
















 




	 	3.	 	Amendment to Section 13.3(e). Section 13.3(e)
    of the Agreement shall be replaced in its entirety to read as
    follows:


    In the event that (i) the Trial Results Review Date shall
    not have occurred on or before March 31, 2007, or
    (ii) Endo determines, in its sole discretion, to terminate
    the Agreement during the sixty-day period beginning on the Trial
    Results Review Date, Endo shall have the right to terminate this
    Agreement effective upon 10 days’ written notice with
    no further rights or obligations hereunder (other than those
    rights or obligations which are expressly indicated herein to
    survive termination or expiration of this Agreement); provided
    that such written notice is delivered to DURECT no later than
    April 30, 2007.







 






	 	4.	 	The term “Trial Results Review Date” shall be
    substituted in lieu of “Trial Commencement Date”
    throughout the Agreement.





 






    Except as set forth above, all other terms of the Agreement
    shall remain the same. Please sign below to indicate Endo’s
    agreement to the foregoing.



 



	 	Very truly yours,


/s/ JAMES E. BROWN              

James E. Brown

President and CEO


 



AGREED TO BY ENDO:


 


	BY:	 	/s/ PETER A. LANKAU  
 
 
 
 
 
 

Peter A. Lankau

President and CEO









Date:    1/23/06