Pfizer promotes 'underappreciated' R&D pipeline
This article was originally published in Scrip
The new in-house buzzword for Pfizer's research and development pipeline isn't catchy, but it seems to accurately describes investor attitudes toward the pharmaceutical giant's R&D programs: underappreciated.
Pfizer has made investments in high-value drug classes, but it will not be the first to market with cancer immunotherapies or PCSK9 inhibitors to treat high cholesterol, so the company is betting on a pipeline of what it hopes will be best-in-class assets. Pfizer has a history with that kind of strategy – the company's mega-blockbuster Lipitor (atorvastatin) wasn't the first statin launched commercially, but it had the highest sales totals of any high cholesterol drug in its class.
"I do think the Pfizer pipeline is somewhat underappreciated," worldwide R&D president Mikael Dolsten said during the company's presentation on 13 January during the 33rd Annual JP Morgan Healthcare Conference in San Francisco.
And in a 14 January interview with Pfizer PharmaTherapeutics R&D head Rod MacKenzie and Pfizer BioTherapeutics R&D head Jose-Carlos Gutierrez-Ramos during the JP Morgan conference, Dr MacKenzie echoed Dr Dolsten's comment, telling Scrip that the company's portfolio is "underappreciated."
80 programs in the clinic
Pfizer's R&D executives point to a pipeline comprised of 214 discovery projects, 35 Phase I programs, 22 Phase II therapeutic candidates, 23 Phase III assets and six products awaiting regulatory approvals, including both new molecular entities and new indications for already approved drugs. The company plans to initiate up to 20 new Phase II/III registrational studies and seek approval for as many as 15 new drugs or indications during the next four years.
"We think we're in a pretty robust position," Dr MacKenzie said.
The focus on pipeline prospects in 2015 follows Pfizer's failed attempt to buy AstraZeneca last year. The proposed acquisition was based on UK-based AstraZeneca's attractive ex-US tax structure as well as its R&D pipeline, especially in the oncology arena, since Pfizer is trying to increase the size of its cancer franchise (scripintelligence.com, 14 May 2014).
Evercore ISI analyst Mark Schoenebaum said during a recent video update about the stocks he covers that Pfizer's pipeline "is better than people think, but not the best" and he agreed with company executives that the targeted cancer drug Ibrance (palbociclib) is the next big R&D catalyst in Pfizer's portfolio. Dr Schoenebaum forecast as much as $4bn in annual sales for the CDK4/6 inhibitor at its peak.
Pfizer revealed in early January that the US FDA will not require an advisory committee meeting prior to the 13 April Prescription Drug User Fee Act (PDUFA) date for the Ibrance new drug application (NDA). The company is seeking FDA approval for Ibrance as a first-line treatment in combination with letrozole for postmenopausal women with estrogen receptor-positive, HER2-negative advanced breast cancer (scripintelligence.com, 9 January 2015).
Still, Pfizer's stock price reflects the attitude of investors waiting for evidence that the company has rejuvenated its pipeline with potentially market-leading drug candidates.
Even at a new one-year high of $33.10 per share on 20 January, Pfizer's stock is trading at almost half of the immuno-oncology leaders Merck & Co and Bristol-Myers Squibb, whose programmed death-1 (PD-1) checkpoint inhibitors Keytruda (pembrolizumab) and Opdivo (nivolumab) were approved to treat advanced melanoma in the US in 2014 (scripintelligence.com, 23 December 2014).
Pfizer recently acquired global co-development and co-commercialization rights to the Phase II PD-1 ligand (PDL-1) inhibitor avelumab (MSB0010718C) from Merck KGaA (Merck Serono in the US) as a treatment for multiple tumor types, but the partners remains far behind Merck & Co and Bristol-Myers as well as AstraZeneca and Roche, which have PDL-1 inhibitors in Phase III development (scripintelligence.com, 17 November 2014).
However, Pfizer hopes to gain a foothold in the immuno-oncology market not just with its PDL-1 inhibitor avelumab, but with additional therapeutic candidates that target the immune system.
"The Merck Serono deal was the nucleus for the rest of immuno-oncology in the company," Pfizer's Dr Gutierrez-Ramos said.
The company also has cancer vaccines, chimeric antigen receptor T-cell (CAR-T) therapies and agents directed against the immune system targets 41-BB and OX40 in its pipeline. Pfizer plans to begin single-agent clinical trials for avelumab and other immunotherapies in 2015. The company's second wave of immuno-oncology development will combine avelumab with the other immunotherapy agents as well as with targeted cancer therapies, including antibody-drug conjugates, bi-specific antibodies and Pfizer's Inlyta (axitinib) and Xalkori (crizotinib).
"We couldn't do this, never mind PDL-1, without the investments that we have made in immuno-oncology over the past five years," Dr Gutierrez-Ramos said.
PCSK9 investments
Pfizer also believes that its substantial investments in PCSK9 inhibition for high cholesterol will pay off despite the lead that Amgen's evolocumab and alirocumab from Regeneron Pharmaceuticals and Sanofi have over the company's Phase III biologic candidate bococizumab.
The stock prices for Amgen and Regeneron, who have biologic license applications (BLAs) pending with the FDA for the evolocumab and alirocumab, are trading at almost five times and 13 times as much as Pfizer's shares based in large part on expectations for the injectable cholesterol-lowering drugs (scripintelligence.com, 10 November 2014 and 12 January 2015).
However, Pfizer has designed a Phase III program for bococizumab that it claims is larger in scope than the big Phase III programs for the Amgen and Regeneron/Sanofi biologics.
"The extent of the outcomes data is really going to make a big difference to payers," Dr MacKenzie said.
Pfizer also is developing a bococizumab formulation with partner Halozyme that requires injections only once per month rather than once every two weeks, and the company plans to begin clinical trials in 2015 for a small molecule PCSK9 inhibitor. A PCSK9 vaccine also is in preclinical development, but is not as advanced as the oral pill.
"We're the only company with an oral PCSK9 close to the clinic and we're going into humans this year," Dr MacKenzie noted.
Other R&D highlights
Pfizer has clinical milestones in the works across all of its therapeutic areas in addition to oncology and cardiovascular medicine, including inflammation, vaccines, neuroscience and pain, rare diseases and biosimilars.
*The twice-daily oral janus kinase (JAK) inhibitor Xeljanz (tofacitinib) is approved to treat rheumatoid arthritis, but Pfizer is pursuing additional indications, such as psoriatic arthritis, ankylosing spondylitis and psoriasis (scripintelligence.com, 23 April 2014). The company also is investigating a once-daily version of Xeljanz and it has various second-generation selective JAK inhibitors in preclinical through Phase II development.
*The staphylococcus aureus vaccine SA4Ag, which will advance into Phase IIb studies, is among multiple candidates and approved agents in Pfizer's growing vaccine portfolio anchored by the blockbuster pneumococcal vaccines Prevnar and Prevnar 13. The company gained vaccine assets and manufacturing capabilities in July in a $635m transaction with Baxter (scripintelligence.com, 31 July 2014).
*Pfizer will restart development of tanezumab with Phase III clinical trials in osteoarthritis, chronic low back and cancer pain in 2015 if the company can get the FDA to lift a partial clinical hold on the nerve growth factor (NGF) inhibitor, which was put in place due to worsening of osteoarthritis in some patients (scripintelligence.com, 20 July 2010). Pfizer has learned more about NGF inhibition and which patients to enroll in future clinical trials during the past few years.
*The company has several rare disease programs, including rivipansel for sickle cell anemia, which was licensed from GlycoMimetics. Pfizer hopes to begin a Phase III program in 2015 that was delayed last year due to formulation issues (scripintelligence.com, 29 September 2014).
*With five biosimilars in development, most of which are in Phase III, Pfizer plans to advance its copies of AbbVie's Humira (adalimumab); Roche/Genentech's Avastin (bevacizumab), Herceptin (trastuzumab) and Rituxan (rituximab); and Johnson & Johnson's Remicade (infliximab) in 2015. The company expects to report Phase II proof-of-concept data and Phase III results from it biosimilar programs and win regulatory approvals for some of its biosimilars during the next four years.