For many years Pfizer Vaccines has been a one-trick pony, but now Pfizer Inc. is looking to grow its vaccines business beyond Prevnar and is ready to invest in new, untapped opportunities.

While the company has been dependent solely on Prevnar, the pneumococcal vaccine is no slouch. It’s the best-selling vaccine in the world, but it’s an asset Pfizer gained with the acquisition of Wyeth in 2009. Since then, the company’s focus has remained squarely on Prevnar, launching a new 13-valent version of the vaccine, Prevnar 13, and expanding its use to older adults.

But now, after establishing vaccines as a standalone business unit in 2014, investing in research and acquiring new assets via deal-making, Pfizer is positioning itself to bring a portfolio of vaccines to the market.

The company’s interest in vaccines has been reenergized by disruptive science that is allowing developers to explore new opportunities beyond traditional viral vaccines administered to infants in the months following their birth.

“We think it is just the start of a new era where we will encounter vaccines very early in life, even before birth by vaccination of the mothers, and then supporting us through various vulnerable periods,” President-Worldwide R&D Mikael Dolsten said during a press briefing outlining the company’s vaccines portfolio at the company’s New York headquarters July 21.

Pfizer sees an opportunity to grow vaccines long-term by developing products that address those new untapped areas, for example, a portfolio of vaccines targeting pregnant women and their unborn children and therapeutic vaccines, including therapeutic cancer vaccines.

A Small, But Growing Portfolio

Thanks to the success of Prevnar, Pfizer is one of the top producers among the big pharma that compete in the space, based on sales. It ranks behind GlaxoSmithKline PLC and Merck & Co. Inc. and about on par with Sanofi. GSK grew its vaccines business substantially after completing the acquisition of Novartis AG’s vaccines business earlier this year, surpassing Merck as the leader ([A#00150511012]).

Top Vaccines Manufacturers By 2014 Sales

GlaxoSmithKline: £3.7 billion ($5.8 billion) pro forma, including Novartis
Merck: $5.3 billion
Pfizer: $4.48 billion
Sanofi: €3.97 billion ($4.34 billion)

Pfizer’s vaccines generated $4.48 billion in 2014, representing growth of 13%, and coming almost entirely from Prevnar and the newer 13-valent version Prevnar 13, which has expanded with a new indication for adults 50 and older. Growth jumped in the second half of the year following a recommendation from the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) in favor of routine use of Prevnar 13 in adults 65 and older in August 2014, a key to widespread uptake ([A#14140814003]).

Pfizer launched a second vaccine, Trumenba, a meningitis vaccine against meningococcal Serogroup B, in November following an accelerated approval by FDA. The agency also approved a rival vaccine, GSK’s Bexsero, in January under accelerated approval, driven by the urgent need for a vaccine following an outbreak of the disease on college campuses. Meningitis can be deadly, but it’s rare and the ACIP hasn’t advocated in favor of routine administration of the vaccines, which may limit their uptake.

ACIP issued a final recommendation in June that decisions to vaccinate adolescents and young adults 16 through 23 years of age against serogroup B meningococcal disease should be up to the individual, an improved outcome for industry versus an earlier opinion that they should only be administered to people at risk ([A#14150227002]).

The commercial potential for the meningitis vaccines remains limited for now and Sanofi’s Menactra and GSK’s Menveo are available for serotypes A, C, Y and W-135.

Pfizer also added two marketed vaccines to its portfolio last year through a $635 million transaction with Baxter International Inc. The company bought Baxter’s NeisVac-C, which protects against meningitis group C meningococcal infections, and FSME-IMMUN/TicoVac, which protects against tick-borne encephalitis. Both vaccines are sold primarily in Europe ([A#14140730003]).

Earlier this year, the company also picked up two vaccines from GSK, the sale of which was required by competitive authorities as part of the GSK/Novartis transaction. The company announced a deal in June to buy GSK’s quadrivalent meningitis vaccines Nimenrix and Mencevax for $130 million ([A#14150622001]). The niche products had just $34 million in sales in 2014.

“In the last 18 months, our vaccines business has grown significantly from a single vaccine, Prevnar, to a diverse portfolio,” said President- Pfizer Vaccines Susan Silbermann, though she noted the deal with GSK hasn’t yet closed; it’s expected to close later this year. The vaccines business includes 4,500 employees worldwide, including R&D, manufacturing, regulatory and commercial.

Big Potential For Staph Aureus Vaccine

But Pfizer has bigger ambitions for vaccines in the future. Its next big opportunity could be a vaccine against the nasty bacterial infection Staphylococcus aureus, increasingly resistant to antibiotics and sometimes deadly. Some 10,000 patients die every year in the U.S. due to resistant staph infections, according to Pfizer.

After a couple of failed attempts by industry to develop a Staph aureus vaccine, including one by Merck, Pfizer now thinks it has the answer.

“Sometimes it’s better to wait a little and study a pathogen a little more closely,” Chief Scientific Officer-Vaccines R&D Kathrin Ute Jansen said. “When you look at the pathogen very closely, Staph aureus has developed a number of variance mechanisms to cause the disease. To be successful, you have to really address this pathogen not just from one side, but multiple sides.”

The company announced in July the initiation of a Phase IIb clinical trial testing the vaccine in patients undergoing elective spinal surgery. The candidate has been granted fast track designation by FDA and the Phase IIb trial, if successful, could be sufficient to secure FDA approval, Jansen said.

The timing for completion of the Phase IIb trial is uncertain because it is an event-driven trial, but Dolsten said it could take two to three years before enough events occur to draw conclusions about efficacy.

Though the study is being conducted in patients undergoing elective spinal surgery, Pfizer expects the vaccine could have broad application to patients undergoing elective surgeries initially and further out to other populations. It takes about two weeks for antibodies to build up following administration, which is one reason Pfizer is focusing on elective surgeries versus emergency surgeries.

“We can envision that if a vaccine like this is proven effective it could have a very widespread use to patients and even health care personnel, but that is not our initial focus,” Dolsten said.

Also for the hospital setting, Pfizer has a vaccine in development for Clostridium difficile, which has also been granted fast track designation from FDA.

Pfizer’s Three Research Focus Areas In Vaccines
Bacterial	Staphylococcus aureus Colstridium difficile Group B streptococcus Next-generation pneumococcal
Viral	Respiratory syncytial virus Cytomegalovirus
Therapeutic	Vaccines-based immunotherapy regimens (VIBR) Opportunistic (PCSK9)
Source: Pfizer, July 21, 2015

A Portfolio Of Vaccines Targeted To Pregnant Women

Further out, the big pharma is additionally developing a portfolio of vaccines targeted to pregnant women and intended to protect either the mothers or their unborn child. The first maternal vaccination candidate – a vaccine against group B streptococcus – could reach the clinic in late 2016 or early 2017.

In addition to the vaccine against group B strep, two other vaccines still in preclinical development include a vaccine against the life-threatening respiratory syncytial virus (RSV) and cytomegalovirus (CMV), which can cause hearing loss or mental retardation.

Maternal vaccinations could represent a new long-term growth opportunity for vaccines manufacturers because there are currently no vaccines approved for pregnant women. The idea is that by vaccinating pregnant women, mothers would be able to pass on protective antibodies to their unborn children, protecting them either while in the womb if necessary or as soon as they are born.

While there are currently no vaccines approved for pregnant women, Jansen said FDA and other regulatory agencies are actively working to create a path forward to develop vaccines targeted for use in pregnant women. Additionally, flu vaccines and diptheria, pertussis and tetanus vaccines are now routinely recommended for pregnant women, driving home the importance of such treatments.

“What we have also seen over the last few years is a change in the scientific environment and new scientific achievements that have fueled our interest in a strategy to actually target diseases that are important either for the pregnant mother herself or the unborn child or very young child,” Jansen added.

In the case of group B streptococcus, she noted that the highest burden of disease in newborn infants is within just a couple of days of birth, before a post-birth vaccination would be possible.

The impact of RSV is also most severe in newborn infants in the first months of life, she added

“If we find a way to immunize the pregnant mother so that there is sufficient protective antibody on board when the baby is born we have an opportunity to reduce the large amount of infections or at least severe lower respiratory tract disease that leads to hospitalization,” she said. There are about 100,000 hospitalizations in the U.S. each year caused by RSV.

Pfizer gained the CMV vaccine candidate through the acquisition of a majority stake in Redvax GMBH early this year [See Deal].

Rivals are also looking to take advantage of the opportunity, however. GSK has a maternal RSV vaccine in Phase I development.

Renewed Interest In Therapeutic Cancer Vaccines

Pfizer’s progress in vaccines also extends to therapeutic vaccines, including cancer vaccines, which have been the subject of much interest within the industry, although limited tangible success.

“The promise of the new area of cancer medicine, we think opens up this avenue to look upon not only cancer medicines, but cancer vaccines as the ultimate way you are getting really long lasting and in some cases curative outcomes,” Dolsten said.

The company expects to bring its therapeutic cancer vaccine into clinical testing later this year, with an emphasis initially on prostate cancer.

The product is a multi-component vaccine, according to Jansen. “Not only does the vaccine induce a T-cell response, but we also have components in there that maintain the T-cell response and we have components in the vaccine that … also have the opportunity to take care – at least based on our preclinical work – of this immunosuppressive tumor environment,” she said. “It is a very new concept. It is, in a single vaccine, something like a combination therapy.”

A cancer vaccine like this one could potentially be used in combination with immune checkpoint inhibitors like PD-1/L1 blockers, the company said. While those products help to reactivate the immune system to fight cancer by lifting the immune system’s brakes, many patients still don’t have enough trained immune cells to engage the tumor.

“The vaccine has the unique opportunity to retrain the immune system and expand the available immune cells that can attack the tumor,” Dolsten explained. The hope is to induce long-lasting immune responses that may control the tumor for years or even eradicate it, he added.

Pfizer has a growing pipeline of immuno-oncology drugs in development with which it could test a therapeutic vaccine in combination. The company has said it will have six immunotherapy agents in clinical development this year, including the PD-L1 avelumab, which it licensed from Merck KGAA last November Also see "Pfizer Oncology Strategy: An Investment Starts To Pay Off" - Pink Sheet, 22 June, 2015..

Dolsten said Pfizer decided to focus on prostate cancer first with its new vaccine because it includes three distinct proteins that are highly expressed in prostate cancer cells. The “sweet spot” for a vaccine might fall between hormonal therapies and chemotherapy within the standard of care for prostate cancer.

A similar approach could be used to treat other cancers, Jansen added. “We have our platform and so we can adapt this platform to any cancer we want to address as long as we know the tumor antigens that are expressed in these cancers,” she said.

Pfizer is focusing mainly on therapeutic cancer vaccines, but will explore other therapeutic vaccines opportunistically, according to Dolsten. One such project is a PCSK9 vaccine in preclinical development to lower cholesterol, a new mechanism of action being explored compared to the monoclonal antibodies. Sanofi and Regeneron Pharmaceuticals Inc.’s Praluent (alirocumab) was the first PCSK9 inhibitor approved in the U.S. July 24 ([A#14150724005]). Pfizer’s bococizumab is likely to be third in that class.

The company also has therapeutic vaccines in development for smoking cessation and allergic rhinitis/asthma.

Pfizer has a long way to go to prove it can bring innovative new vaccines to the market, but if successful, the company may have a winning growth strategy on the way.

Pfizer Vaccines: A Budding Portfolio Of Long-Term Opportunities

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