R&D budget: $8.65 billion
Change from 2018: +8%
Total 2019 revenue: $51.8 billion
R&D budget as percentage of revenue: 16.7%
2019 was a transitional year for Pfizer, with CEO-elect Albert Bourla charged with overseeing the implementation of a revamp of the company—started under his predecessor Ian Read—to refocus it on innovative drug discovery and development.
Pfizer has been contending with a fierce patent cliff over the last few years, which continued in 2019 with the loss of protection for blockbuster nerve pain therapy Lyrica (pregabalin) in the US, putting $3.6 billion of its $5 billion sales under generic threat. That’s the last expiry until 2026, so the company can now concentrate on growth, and ploughing cash into its pipeline as it sets out to meet its "15 in five" objective of bringing 15 new blockbuster medicines to market between 2018 and 2022.
Last year’s spend rose 8%, and Pfizer also fleshed out its pipeline with the $11.4 billion acquisition of Array Biopharma, adding lead asset Braftovi (encorafenib) which has since been approved in combination with cetuximab for relapsed, BRAF-positive colorectal cancer. Pfizer has also agreed to spin out and merge its generic business Upjohn with Mylan, and combine its consumer health ops with those of GlaxoSmithKline, as part of its strategy of becoming an innovation-focused company.
Bourla says the revamp of R&D is already paying off in terms of phase 2 project success rates—now close to 50% versus 15% a few years ago—and the number of NMEs reaching market. Part of that improvement has come from reorganizing all its business units into biotech-like organizations, each responsible for all things from early R&D to commercial and competing for capital allocation. Last year, it also opened the first in a planned network of digital research hubs with a focus on artificial intelligence and big data analytics.
One of the big successes for Pfizer’s R&D ops in 2019 was securing FDA approval for Foldrx-partnered transthyretin stabilizer Vyndaqel (tafamidis) in transthyretin-mediated amyloidosis cardiomyopathy (ATTR-CM), billed as a $1.5 billion potential market. It already seems to be firmly on track for that with first-quarter 2020 sales of $231 million, well ahead of expectations, although COVID-19 is hanging over the roll-out over the remainder of the year.
There was also a string of approvals for biosimilars and lime extensions to existing drugs, including an FDA approval in metastatic castration-sensitive prostate cancer for blockbuster Xtandi (enzalutamide), a green light for Merck KGaA-partnered PD-L1 inhibitor Bavencio (avelumab) in kidney cancer, and a first-in-class win for the drug in bladder cancer.
Pipeline developments included a filing for Eli Lilly-partnered nerve growth factor inhibitor tanezumab in the U.S. and Europe for chronic pain associated with osteoarthritis in patients who have failed other analgesics. With the finish line in sight, Pfizer has started to talk up the prospects of the drug a little after being reticent before—NGF has been a touch nut to crack and tanezumab posted mixed data that haven’t dispelled safety concerns with the class.
2020 meanwhile could see data from up to 15 proof-of-concept trial readouts, including five pivotal trials, and up to 10 pivotal study starts, according to Pfizer.
There’s a bid to double the eligible patient population for blockbuster breast cancer drug Ibrance (palbociclib), already dominating the CDK 4/6 inhibitor field, into patients with early-stage disease, with trial readouts due later in 2020 and early 2021.
Pfizer’s entrant into the JAK inhibitor category abrocitinib now has positive top-line phase 3 data in atopic dermatitis, a use that sidesteps the increasingly competitive market for the class in rheumatoid arthritis. The study compared the oral drug to Sanofi’s big-selling injectable Dupixent (dupilumab), with improved efficacy on some secondary endpoints like itching and what seems to be more rapid onset of action.
Other programs highlighted by the company in recent R&D updates include bepocitinib, a topically-administered TYK2/JAK1 inhibitor for psoriasis and atopic dermatitis, and oral TYK2 drug PF-06826647 for psoriasis, both in phase 2. The company’s ‘immunokinase’ programs also include JAK3 inhibitor PF-06651600 in a mid-stage trials for alopecia areata and vitiligo—new indications for the JAK class—with readouts due in 2020/2021.
Combined ACC/DGAT2 inhibitor PF-07055341 recently cleared a proof of concept study for non-alcoholic steatohepatitis (NASH), while Akcea-developed ANGPTL3 antisense drug AKCEA-ANGPTL3-LRx met its primary endpoint and multiple secondary endpoints in a phase 1/2 trial and will be developed further for severe hypertriglyceridemia and cardiovascular risk reduction.
Like Swiss rivals Novartis and Roche, Pfizer has made building a position in gene therapy a pillar of its R&D strategy, spearheaded by its 2016 acquisition of Bamboo Therapeutics, although its lead programs look unlikely to be first to market.
Heading the portfolio is hemophilia B candidate fidanacogene elaparvovec in phase 3—in a race with UniQure’s etranacogene dezaparvovec—and that could soon be joined by hemophilia A therapy SB-525, after it posted promising phase 1/2 last year. Biomarin is out in front at the moment in hemophilia A with its valrox therapy already submitted to the FDA.
Pfizer’s Duchenne muscular dystrophy gene therapy is also due to start phase 3 in the second half of the year, but once again is a little behind Sarepta whose own candidate is already in late-stage development. A Wilson’s disease candidate is also approaching the clinic.
Turning to vaccines, Pfizer’s 20-valent Prevnar is due to be filed before year-end, as it tries to stay one step ahead of Merck, whose 15-valent V114 is also set to be submitted to the FDA this year. It’s also just had proof-of-concept data for its maternal respiratory syncytial virus (RSV) vaccine ahead of a planned phase 3 trial.
There have been setbacks as well, notably sickle cell disease asset rivipansel, which missed the mark in a phase 3 study and was dropped, as well as failed trials for Bavencio in head and neck, ovarian and gastric cancer, and Lyrica in a severe form of epilepsy.
Finally, Pfizer’s coronavirus vaccine alliance with BioNTech is now at the clinical testing stage, with millions of doses due to be produced by the end of the year, which could rise to hundreds of millions of doses in 2021 if trials are positive. They are the only companies testing a self-amplified mRNA candidate, which in theory could allow lower dosing which would in turn boos the number of doses available. Pfizer also has an antiviral protease drug heading towards the clinic in August or September.
There has been a “brief pause” in clinical trial recruitments due to the pandemic, said Bourla at the end of April, but he stressed that most of Pfizer’s key pipeline programs continue to move forward on track. In May, Pfizer said it has recently restarted patient enrollment across its portfolio of clinical trials and resumed starting new studies.
Check out Pfizer’s pipeline here.