By Jonathan D. Rockoff, Shayndi Raice and Dana Mattioli 

Shire PLC is buying NPS Pharmaceuticals Inc., a maker of treatments for rare diseases, for $5.2 billion, returning to deal-making with the help of the breakup fee it received from one-time suitor AbbVie Inc.

The all-cash deal, for $46 a share, would hasten the Irish company's pivot to drugs for rare conditions and bolster its portfolio of therapies for gastrointestinal disorders like the ones treated by NPS's two drugs, said Flemming Ornskov, Shire's chief executive.

"It is another step in the direction of becoming a biotech," he said in an interview.

The agreement is Shire's first major deal after AbbVie's attempts to acquire Shire fell apart last October. Dublin-based Shire received a breakup fee of $1.6 billion after AbbVie walked away from the so-called tax-inversion deal. AbbVie scrapped the acquisition after the Obama administration took steps to deter such tax-lowering deals.

Dr. Ornskov indicated Shire would keep hunting for more deals.

The company has been aiming to use the breakup fee to restart its shift from drugs for common conditions like attention-deficit disorder toward drugs for rarer diseases. Dr. Ornskov said combining NPS's two drugs with Shire's existing sales force could eventually yield blockbuster sales for each of the NPS therapies.

NPS, of Bedminster, N.J., specializes in rare-disease drugs. Its Gattex injections treat a potentially deadly bowel disorder that diminishes the body's ability to absorb nutrients and fluids. Gattex, which costs $376,200 a year, had $67.9 million in sales during the first nine months of 2014. NPS earned $157.4 million in total revenue during the period.

The market for rare-disease treatments is considered attractive, despite a small number of patients, because companies can command prices in the hundreds of thousands of dollars--as is the case with Gattex. Sales of so-called specialty drugs are forecast to reach $162 billion in 2018, up from $108 billion in 2013 and $81 billion in 2008, according to Credit Suisse.

Despite the cost, insurers are usually willing to pay for the therapies because they have few members who need them and the drugs can be lifesaving. Also making the market attractive is a lack of competition for the drugs.

NPS also has another rare-disease drug that could generate hundreds of millions of dollars in revenue. The drug, which treats a hormone condition called hypoparathyroidism, is already approved in Europe; the U.S. Food and Drug Administration is due to decide soon whether to approve the drug, under the name Natpara.

One risk that Shire could be taking by buying NPS before the FDA's decision: the agency could potentially limit patient use of Natpara to two years, which could limit sales. Dr. Ornskov said Shire reviewed NPS's discussions with the FDA. "We are very confident in what we've seen, and that was a risk worth taking," he said.

The acquisition of NPS would be accretive to Shire in 2016 and is expected to close in the first quarter of this year, Dr. Ornskov said.

Last week, The Wall Street Journal reported that NPS was looking for a buyer.

Dr. Ornskov said he believes sales of Gattex's two drugs could benefit from the bigger heft of Shire's sales force. Shire has about 100 sales representatives selling its own gastrointestinal treatments, including Lialda for ulcerative colitis, one of Shire's top-selling drugs.

Shire, which has a market capitalization of $42 billion, reported $4.4 billion in total revenue during the first nine months of 2014.

A Shire-NPS deal suggests 2014's record year of deal-making in the biotechnology and pharmaceutical industries remains strong in the new year. In 2014, biotech and pharmaceutical companies announced deals valued at $265.7 billion, the biggest sum since at least 2000, according to Dealogic.

Many analysts expect the mergers and acquisitions to continue as long as debt remains cheap and companies try to reposition themselves in a changing health-care market.

Write to Jonathan D. Rockoff at Jonathan.Rockoff@wsj.com, Shayndi Raice at shayndi.raice@wsj.com and Dana Mattioli at dana.mattioli@wsj.com

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