6. AstraZeneca

The U.K.-headquartered Big Pharma spends a meaty 25.6% of its total revenue on research.

R&D budget: $5.89 billion
Change from 2015: Down 1.7%
Total 2016 revenue: $23 billion
Percentage of revenue: 25.6%

AstraZeneca had a pretty rough few years of R&D setbacks and failures up until 2012, when its former chief, David Brennan, was all but pushed out as a result. 

Things seem to have steadied somewhat since Pascal Soriot took the helm, though, and he has been bullish on its future. Relatively speaking, the U.K.-headquartered Big Pharma still spends big on research, a meaty 25.6% of its total revenue (of just under $23 billion), making it one of the largest in percentage terms.

But the company still saw some setbacks in 2016, the biggest of which was the unexpected FDA complete response letter to its $2.7 billion hyperkalemia candidate ZS-9, coming after manufacturing issues at its newly acquired biotech pushed back its approval and gave rival Relypsa time to consolidate its position on the market.

In fact, in early 2017, it did manage to get the drug recommended for use in Europe, only to be hit by a second CRL in March.

RELATED: AstraZeneca’s $2.7B ZS-9 rejected again by FDA

AstraZeneca also had continuing issues with its PD-L1 candidate durvalumab, with rival Roche beating it to market with Tecentriq (atezolizumab)‎ last year and Pfizer and Merck KGaA getting an FDA nod for their checkpoint inhibitor Bavencio this year; AZ will now be fifth to market overall in the PD-1/PD-L1 market.

It also saw the agency place a partial clinical hold on a phase 3 trial of durvalumab, which restricted the pharma from adding new patients to clinical trials, as monotherapy and in combination, in head and neck squamous cell carcinoma, while adverse bleeding events were also observed in several late-stage tests.

Its MEK 1/2 inhibitor selumetinib also hit trouble after failing to improve either progression-free or overall survival in patients with KRAS mutation-positive non-small cell lung cancer last fall in another phase 3 setback.

And there was a familiar story back in February when its CTLA-4 drug tremelimumab flunked a solo challenge for mesothelioma, a form of lung cancer associated with asbestos and notoriously tough to treat.

It also lost talent when its head of research, Yong-Jun Liu at MedImmune, AZ’s biologic arm, left the company. Liu, one of the world's most prolific researchers in immunology, was poached by European Big Pharma rival Sanofi.

But not all are seeing doom and gloom in AstraZeneca's pipeline: Analysts at Leerink came out to bat for the Big Pharma last year, seeing a trial that puts tremelimumab and durvalumab together as a first-line treatment in lung cancer as being a potential major therapy (worth $4 billion at peak) for the company, especially after Bristol-Myers Squibb’s shock phase 3 lung cancer flop with Opdivo (nivolumab) last year.

And despite a littered pipeline of biopharma failures, including Lilly’s solanezumab, the U.S. pharma and AZ signed a new R&D pact on amyloid drug MEDI1814, which is currently in phase 1 trials and touted as “a potential disease-modifying treatment for Alzheimer’s disease.”

>> Check out AstraZeneca’s pipeline.

6. AstraZeneca