With Shire, Allergan would gain the ADHD drug Vyvanse, which drew $1.23 billion in 2013 revenue. Shire also focuses on rare diseases, with drugs like Elaprase for an enzyme deficiency called Hunter syndrome and Replagal for Fabry disease drawing $546 million and $468 million last year, respectively.
And the 12.5 percent Irish corporate tax rate can't be ignored—despite Pyott's comments earlier this year that he's unlikely to step in line with industry trends and seek acquisitions there.
Read MorePharma M&A is back—Can it cure the sector's ills?
Allergan, whose most famous product is the wrinkle buster Botox, had cash and equivalents of $3.05 billion at the end of 2013, and revenue for the year of $6.3 billion. Shire had $4.9 billion in 2013 revenue.
Cacciatore concedes that "given the very rapid and innovative approach that Valeant has taken, it is indeed most likely that it will successfully consummate this transaction." But he also stresses that investors shouldn't count Allergan out just yet.
Allergan and Shire declined to comment. Valeant didn't immediately respond. Pershing Square, Allergan's largest shareholder, also declined to comment. Pershing's Bill Ackman is aligned with Valeant on the deal, implying that at least his nearly 10 percent of the stock would not be behind a deal for Shire.
Allergan adopted the poison pill—officially known as a shareholder rights plan—on Tuesday night. It's designed to prevent Ackman from acquiring more shares. Allergan noted that the poison pill wasn't designed to prevent an acquisition that its board deemed favorable—just to provide it enough time to assess any offer.
—By CNBC's Meg Tirrell.