When Amgen agreed to nab Onyx for $10.4 billion back in 2013, some analysts were predicting up to $3 billion in peak sales for multiple myeloma drug Kyprolis—but Kyprolis didn’t come anywhere close. (Amgen)

Deal size: $10.4 billion
Date announced: August 25, 2013

When Amgen agreed to nab Onyx for $10.4 billion back in 2013, multiple myeloma drug Kyprolis—central to the deal—was on a tear. After generating $64 million in its first partial year on the market, it had nearly doubled that tally with $125 million in the first few months of 2013.

Amgen, with extensive experience in running clinical trials and marketing drugs in the cancer and cancer side-effects arena, figured it could not only keep the ball rolling, but accelerate growth through promotion and label expansion. Its sales and distribution network in Europe was a nice plus, too.

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"Amgen has a unique opportunity to add value to Kyprolis, a product which is at an early and promising stage of its launch," CEO Bob Bradway said in a statement the day the companies unveiled the deal.

Analysts only expected that Kyprolis’ hot streak would continue as well, pegging 2019 sales at $2 billion to $2.4 billion, with some predicting up to $3 billion in peak sales. Particularly with Amgen’s top sellers staring down a future full of biosimilar competition, it sounded like a nice prospect.

Only, Kyprolis didn’t get there—or come anywhere close. With $778 million in worldwide sales through the first nine months of the year, Kyprolis is in position to eke its way across the blockbuster barrier in 2019 for the first time. In the U.S., third-quarter sales totaled $163 million, less than $20 million ahead of where they were during the same period last year.

RELATED: Amgen talks up Plan B as Kyprolis fails key first-line myeloma trial

One reason? Those line extensions didn’t exactly go as planned. In 2016, Kyprolis flopped a phase 3 trial in newly diagnosed patients, missing its chance to move in the front-line setting, where there are more patients who stay on therapy for longer.

And then there are Kyprolis’ myeloma competitors, which have multiplied in recent years. The company has at times maintained that newcomers have not specifically hurt Kyprolis’ opportunity, but Amgen has still watched Celgene’s Pomalyst—launched within a year of Kyprolis—cruise to blockbuster status, with $1.84 billion in sales through the first nine months of this year.

More recently, J&J’s Darzalex has leapfrogged from a fourth-line treatment to a first-line standout, racking up $2.17 billion over 2019’s first three quarters.

So should Amgen never have gone after Kyprolis, or was it the Big Biotech’s postdeal execution that hurt the drug’s expansion opportunities?

That’s still up for debate. Amgen, for its part, pointed to double-digit volume increases for the drug on its third-quarter earnings conference call.

"Kyprolis grew 15% year-on-year driven primarily by 12% volume growth with the breadth of prescribers continuing to increase. We continue to invest behind Kyprolis and add to the growing body of clinical evidence demonstrating Kyprolis' important role in the treatment of multiple myeloma," the company said in a statement, adding that the Onyx deal also brought it an 8% royalty worldwide on Pfizer breast cancer blockbuster Ibrance.

But no matter how you slice it, $10.4 billion is an awful lot to pay for a company whose star product has brought in a combined $4.19 billion through its first six years of ownership—and it’s difficult to argue that Amgen, which is still in need of biosimilar defense, couldn’t have spent that money more effectively elsewhere.