Pfizer 2018: Blockbusters and biosimilars
While advancing original biologics and new molecular entities, Pfizer also has been gaining rapid approvals of biosimilar drugs and has reorganized business units for future success.
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|Product||2017 Sales||2016 Sales|
|Prevnar, Prevenar 13||$5,601||$5,718|
|Refacto AF, Xyntha||$551||$554|
All sales are in millions of dollars.
|1H 2018||1H 2017|
All figures are in millions of dollars, except EPS.
For Pfizer, 2017 was a year when the company continued to drive growth in many anchor brands, received a record number of product approvals, made significant advances in the R&D pipeline, and further strengthened the culture. But midway through 2018, the company made some significant restructuring changes to the businesses in advance of the U.S. patent expiration for Lyrica and in anticipation of “a higher and more sustained revenue growth profile” after 2020.
“In 2017, we continued to invest in our business – including funding the discovery and development of potentially life-changing treatments – while simultaneously returning $12.7 billion directly to shareholders through a combination of dividends and share repurchases,” says CEO Ian Read.
At Pfizer, Read says, more than 90,000 colleagues “come to work with a singular purpose: to innovate to bring therapies to patients that significantly improve their lives. This unwavering focus on patients is at the core of who we are as a company. It drives the discovery of life-changing innovations. It fuels our passion for improving global health. It encourages collaboration, thoughtful risk-taking and diversity of thought. And in 2017, it enabled us to build on our already formidable strengths – world-class science, industry-leading products, prudent capital allocation, and our unique OWNIT! culture – to deliver another strong year for our company and position us to capitalize on exciting new growth opportunities in 2018 and beyond.”
In July 2018, Pfizer announced a plan to organize for future growth, forming a New Hospital Business unit within its Innovative Medicines medicines unit to focus on the significant role of hospitals in healthcare systems. The company is being organized into three businesses: a science-based Innovative Medicines business which will now include biosimilars and a new hospital business unit for anti-infectives and sterile injectables; an off-patent branded and generic Established Medicines business operating with substantial autonomy within Pfizer; and a Consumer Healthcare business. These changes will be effective at the beginning of the company’s 2019 fiscal year.
“This new structure represents a natural evolution of these businesses given the ongoing strength of our in-market products and our late-stage pipeline and the expected significant reduction in the impact of patent protection losses post-2020 following the loss of exclusivity for Lyrica in the U.S which is expected to occur in or after December 2018,” Read says. “As we transition to a period post-2020 where we expect a higher and more sustained revenue growth profile, we see this new structure better positioning each business to achieve its growth potential.”
The Innovative Medicines business will include all of the current Pfizer Innovative Health business units as well as a new Hospital Medicines business unit that will commercialize Pfizer’s global portfolio of sterile injectable and anti-infective medicines, which management says will allow for better focus and customer centricity.
Pfizer will also incorporate the biosimilar portfolio into the Oncology and Inflammation & Immunology business units. According to Pfizer executives, these units possess significant therapeutic area expertise in the medical, commercial, and patient experience domains and will provide a strong commercialization platform for these medicines.
The growth fundamentals for the Innovative Medicines business are strong with an aging population that is leading to increasing demand for new innovative medicines and quickly advancing biological science that is delivering breakthrough solutions. With a robust portfolio of growing in-market products, a new wave of expected launches starting in 2020, and a strong pipeline, Pfizer believes the company is well positioned for growth in this business.
Established Medicines will include the majority of Pfizer’s off-patent solid oral dose legacy brands such as Lyrica, the cholesterol medication Lipitor, the antihypertensive Norvasc, and the erectile dysfunction drug Viagra as well as certain generic medicines. This business will operate in all world regions. To allow this business to act with speed and flexibility, Established Medicines will have distinct and fully dedicated manufacturing, marketing, regulatory and with some exceptions enabling functions that will enhance its autonomy and position it to operate as a true stand-alone business within Pfizer.
Following the impact of the expected loss of exclusivity of Lyrica in the United States during or after December 2018, Pfizer expects that the Established Medicines business has the potential to generate sustainable modest revenue growth. Company executives say urbanization and the rise of the middle class in emerging markets, particularly in Asia, are providing additional access opportunities and generating significant demand for branded and generic established medicines.
“As a leading pharmaceutical company in Asia and particularly in China, Pfizer believes it is well-positioned to be a leader in this significant and rapidly growing market,” management says.
According to Albert Bourla, chief operating officer, the redesign ‘gives us a sharper focus on diverse patients in diverse markets. In addition, the structure will enable the Established Medicines business to optimize its distinct growth opportunities, while also providing the future flexibility to access opportunities that enhance value.”
The Pfizer Consumer Healthcare (PCH) business will include all of Pfizer’s over-the-counter medicines. Pfizer executives say PCH will continue to operate relatively autonomously with dedicated manufacturing and regulatory capabilities.
“While the fundamentals for growth are strong in the PCH business, they differ from the two prescription medicine businesses,” Pfizer leadership says. “Trends in consumerism and an increased focus on staying healthy are causing consumers to seek easily accessible health and wellness solutions. With a strong portfolio of global brands that span health and wellness, the company believes this business is well-positioned to continue its growth. Pfizer continues to evaluate strategic alternatives for this business and expects to make a decision in 2018.”
Based on 2017 actual results, the Innovative Medicines business (including Consumer Healthcare) is expected to comprise three-quarters of Pfizer’s revenues, while the Established Medicines business is expected to comprise one quarter. Pfizer will provide financial reporting to reflect this reorganization beginning with the issuance of first quarter 2019 earnings.
When the changes are effective, John Young and Angela Hwang will lead Pfizer’s Innovative Medicines business and will continue to report to Bourla.
As group president, Young will be responsible for the Internal Medicine, Oncology (including biosimilars), and Rare Disease business units. In addition, he will manage Pfizer’s innovative medicines portfolio across all emerging markets.
Hwang, who will also be group president, will be responsible for the Inflammation and Immunology (including biosimilars), Vaccines, and Hospital Medicines business units. In addition, she will oversee Pfizer’s Consumer Healthcare business.
The Established Medicines business will be led by Michael Goettler, who will become a member of Pfizer’s executive leadership team, reporting to Bourla. Goettler has 23 years of industry experience and joined the company in 2009, as part of the Wyeth acquisition. At Pfizer, he has held a number of senior leader roles with increasing responsibility across multiple therapeutic areas, including primary and specialty care. He ran the Rare Disease Business Unit at Pfizer and initiated the company’s commercial move into gene therapy. He is global president of Pfizer Inflammation & Immunology. Mr. Goettler holds an MBA from the University of Texas at Austin and graduated from the Koblenz School of Corporate Management in Germany.
Financial and product performance
Despite a $3.2 billion negative revenue impact due to the loss of exclusivity of certain brands and the divestment of Hospira Infusion Systems, Pfizer reported flat operational revenue for 2017 due to growth in many of the largest-selling medicines in the portfolio, including Ibrance, Eliquis and Xeljanz. According to executives, all of these products have market-leading positions and many years of patent protection remaining.
Pfizer generated continued growth in emerging markets in 2017, which was up 11 percent operationally compared with the previous year, and in the biosimilars business, which grew 66 percent operationally.
“We remain the No. 1 biosimilars company globally and have taken steps to fortify that leadership, advancing six biosimilar pipeline products during the year through various regulatory and data milestones,” executives say. “We expanded our portfolios for sterile injectables (28 product launches in 2017) and anti-infectives (launching Zavicefta in more than 15 countries and acquiring the rights to Cresemba in Europe, China and APAC). We also have worked diligently toward remediating issues in the legacy-Hospira manufacturing plants and reducing the related product shortages.”
Pfizer reported 2017 revenue of $52.55 billion. Net income came in at $21.31 billion compared with $7.22 billion in 2016. Diluted earnings per share in 2017 were $3.52 compared with $1.17 the previous year. Executives say the differences between 2017 and 2016 net income and EPS can be attributed to the impact of the U.S. Tax Cuts and Jobs Act enacted on Dec. 22, 2017.
In the first half of 2018, Pfizer reported revenue of $26.37 billion, 3 percent more than in the same period of 2017. Net income was about 20 percent more at $7.43 billion in the first half compared with the same period last year. Diluted earnings per share were $1.24 compared with $1.02 in 2017’s first six months.
Pfizer’s top seller during 2017 was the pneumococcal vaccine Prevnar 13/Prevenar 13, which earned $5.6 billion, 2 percent less than in 2016. U.S. revenue for Prevnar 13 decreased 9 percent in 2017 compared to 2016, primarily due to the expected decline in revenues for the adult indication in the United States. “We expect revenues from the adult indication in the U.S. to be flat to declining as the remaining cohort of adults 65 years and over is much more difficult to capture,” Pfizer leaders say.
Prevnar’s global first-half 2018 sales amounted to $2.62 billion, 3 percent more than in the same 2017 period.
Ranking No. 2 for Pfizer in 2017 sales was the neurological drug Lyrica at $5.07 billion, up 2 percent over the previous year. Sales in the first half of 2018 amounted to $2.44 billion, 4 percent less than in first-half 2017.
Sales for the breast cancer drug Ibrance grew 46 percent in 2017 to $3.13 billion. Sales in first-half 2018 were also robust at $1.96 billion, 28 percent more than in the same period last year.
The rheumatoid arthritis drug Enbrel came in at No. 4 with 2017 sales of $2.45 billion, 16 percent less than in 2016. For the first six months of 2018, sales fell to $1.06 billion, a decline of 12 percent compared with first-half 2017.
Sales of the cholesterol medication Lipitor grew 9 percent in 2017 to $1.92 billion. The upward trajectory continued in the first half of this year with $1.03 billion in sales, 22 percent more than during the 2017 first half.
Xeljanz, Pfizer’s new medicine for the treatment of rheumatoid arthritis, psoriatic arthritis and ulcerative colitis, came in at $1.35 billion in 2017 sales, 45 percent more than in 2016. For the first half of 2018, sales of the product were recorded at $788 million, 34 percent more than in the first two quarters of 2017.
Pfizer’s erectile dysfunction drug Viagra generated 2017 sales of $1.2 billion, falling 23 percent year-over-year. Sales in the first half of this year were down to $372 million, 46 percent less than in the same period last year. The decrease occurred after Viagra lost exclusivity in the United States in December 2017.
The cancer drug Sutent was the company’s eighth best-selling drug in 2017, with sales of $1.08 billion, 1 percent less than in 2016. Sales in first-half 2018 were $537 million, 2 percent more than in the first half of 2017.
The smoking cessation drug Chantix/Champix was No. 9 in sales in 2017, generating $997 million, 18 percent more than in 2016. The product generated first-half 2018 sales of $528 million, up 9 percent versus the same period last year.
The Premarin family of hormone replacement products was Pfizer’s 10th best seller in 2017, posting $977 million, 4 percent less than in 2016. Sales in the first six months of 2018 were $401 million, 15 percent less than in the same-time 2017.
The hypertension drug Norvasc ranked No. 11 on Pfizer’s 2017 sales ladder at $926 million, 4 percent less than in the previous year. First-half 2018 sales grew to $526 million, increasing 15 percent over the amount in 2017’s first six months.
The anti-inflammatory drug Celebrex posted 2017 sales of $775 million, rising 6 percent versus the 2016 tally. Sales in the first half of 2018 dropped down to $306 million, 13 percent less than in first-half 2017.
The hemophilia drug BeneFIX produced 2017 sales of $604 million, falling 15 percent off the 2016 pace. Sales in the first six months of this year totaled $288 million, decreasing 5 percent compared to first-half 2017.
The lung cancer drug Xalkori was No. 14 in product sales for 2017, growing 6 percent to $594 million. First-half 2018 sales were 2 percent less than in the same period of 2017, at $290 million.
The recombinant antihemophilic factors ReFacto AF and Xyntha represented the company’s 15th best-selling drug line in 2017 at $551 million, about 1 percent less than the amount generated during 2016. First-half 2018 sales were reported at $271 million, 1 percent more than in the same time frame of 2017.
Sales of the human growth hormone Genotropin in 2017 were $532 million, 8 percent less than in 2016. The product generated $272 million in the first six months of 2018, growing 14 percent versus first-half 2017.
Advancing R&D and the pipeline
One of Pfizer’s most important accomplishments in 2017 was the continued strengthening of the R&D pipeline, “which today is as strong as it’s ever been,” according to Read.
“We have sharpened our focus; we are making better, quicker decisions; and we are accelerating the time it takes to get newly approved products in the hands of patients,” he says. “We advanced 43 assets in our pipeline and received 10 approvals from the FDA – significantly more than we had achieved in any year in the past decade. Over the next five years, we see the potential for approximately 25-30 approvals, of which up to 15 have the potential to be blockbusters – subject to some expected attrition. This presents an unprecedented opportunity to have a life-changing impact on a growing number of patients while creating enhanced value for all of our stakeholders.”
Pfizer has done this while keeping the amounts the company spends on research and development relatively steady. Pfizer spent $7.66 billion on R&D in 2017, compared with $7.87 billion in 2016. During the first half of 2018, R&D spending amounted to $3.54 billion compared with $3.5 billion in the same period last year.
The company continued to advance the pipeline in 2018. In June, Xeljanz, in combination with methotrexate, received approval from the European Commission for the treatment of active psoriatic arthritis (PsA) in adult patients who have had an inadequate response or who have been intolerant to a prior disease-modifying antirheumatic drug (DMARD) therapy. This follows up on the 2017 approval for the treatment of moderate-to-severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more DMARDs.
Xeljanz in August also received marketing authorization in the European Union for treating moderately to severely active ulcerative colitis in adults who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic agent. Xeljanz is the first oral therapy and Janus kinase (JAK) inhibitor to be approved for this patient population.
This makes Xeljanz approved for three indications in Europe. The EC approval follows the review of the application for marketing authorization which included data from three pivotal Phase III studies from the Oral Clinical Trials for tofAcitinib in ulceratiVE colitis global clinical development program (OCTAVE Induction 1, OCTAVE Induction 2 and OCTAVE Sustain), and OCTAVE Open, an ongoing open label long-term extension study.
Also in June, FDA granted priority review for Pfizer’s new drug application for glasdegib in patients with previously untreated acute myeloid leukemia.
Glasdegib is an investigational oral smoothened (SMO) inhibitor being evaluated for the treatment of adult patients with previously untreated acute myeloid leukemia (AML) in combination with low-dose cytarabine (LDAC), a type of chemotherapy.
“Patients with acute myeloid leukemia who are ineligible for intensive chemotherapy are in critical need of new treatment options to improve their overall survival,” says Mace Rothenberg, M.D., chief development officer, Oncology, Pfizer Global Product Development. “In an investigational Phase II study, glasdegib in combination with low-dose cytarabine showed a significant improvement in overall survival compared to patients who received low-dose cytarabine alone. Glasdegib is the first smoothened inhibitor to potentially offer such a benefit to patients with acute myeloid leukemia, and we are proud that our application was accepted by the FDA for Priority Review.”
The submission is based on results from the Phase II BRIGHT 1003 study, a randomized, open-label, multicenter trial investigating glasdegib combined with LDAC (n=88) versus LDAC alone (n=44) in 132 patients with previously untreated AML or high-risk myelodysplastic syndrome (MDS) who were not eligible for intensive chemotherapy.
Results demonstrated a significant improvement in the primary endpoint of overall survival (OS). Median OS was 8.8 months for patients treated with glasdegib plus LDAC compared with 4.9 months for patients treated with LDAC only. This difference represented a 49.9 percent reduction in the risk of death for patients treated with glasdegib plus LDAC (HR: 0.501, 95% CI: 0.334, 0.752, one-sided p-value 0.0003). The BRIGHT 1003 results were presented in 2016 at the 58th American Society of Hematology Annual Meeting.
The Phase III BRIGHT AML 1019 trial (NCT03416179), which is evaluating the addition of glasdegib to intensive or non-intensive chemotherapy in patients with newly diagnosed AML, began enrolling earlier in 2018.
In July 2018, FDA approved Xtandi for treating non-metastatic castration-resistant prostate cancer (CRPC). Xtandi is the first oral treatment that is FDA-approved for non-metastatic and metastatic CRPC.
Xtandi was first approved by the FDA in 2012 for the treatment of patients with metastatic CRPC who had previously received docetaxel, and was granted approval in 2014 for chemotherapy-naïve men with metastatic CRPC.
The updated label is based on results from the Phase III PROSPER trial, which demonstrated that the use of Xtandi plus androgen deprivation therapy (ADT) significantly reduced the risk of developing metastasis or death compared to ADT alone in men with non-metastatic CRPC. The median for the primary endpoint, metastasis-free survival (MFS), was 36.6 months for men who received Xtandi plus ADT compared to 14.7 months with ADT alone (N=1401; HR=0.29 [95% CI: 0.24-0.35]; p<0.0001). The most common adverse reactions (greater than or equal to 10%) that occurred more frequently (greater than or equal to 2% over placebo) in XTANDI plus ADT-treated patients were: asthenic conditions (40 percent vs 20 percent), hot flush (13 percent vs 7.7 percent), hypertension (12 percent vs 5.2 percent), dizziness (12 percent vs 5.2 percent), nausea (11 percent vs 8.6 percent) and fall (11 percent vs 4.1 percent). Grade 3 or higher adverse reactions were reported in 31 percent of men treated with Xtandi plus ADT and in 23 percent of men treated with ADT alone. Data from the PROSPER study were presented at the 2018 Genitourinary Cancers Symposium (ASCO GU) in February and published in the New England Journal of Medicine in June.
“Reducing the risk of disease progression is an important treatment goal in castration-resistant prostate cancer, since the disease becomes harder to treat as it advances,” says Andy Schmeltz, global president, Oncology, Pfizer. “With Xtandi, men with CRPC now have a clinically proven treatment option that reduces the risk of metastasis. This approval delivers on the potential for Xtandi to help men at an earlier stage of the disease, and we are continuing to evaluate the medicine in an extensive development program across additional prostate cancer populations.”
Pfizer developed Xtandi in conjunction with Astellas.
On the biosimilar front, Pfizer continues to gain approvals for these products in the United States and Europe. In July, Pfizer got the OK from the European Commission for Trazimera, a biosimilar of trastuzumab, the active molecule in Roche/Genentech’s Herceptin. The decision marks the approval of Pfizer’s first therapeutic oncology biosimilar.
Trazimera was approved for the treatment of human epidermal growth factor (HER2) overexpressing breast cancer and HER2 overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma. This approval follows the recommendation from the Committee for Medicinal Products for Human Use in May 2018.
According to Richard Blackburn, global president, Pfizer Essential Health Europe, Africa/Middle East and Biosimilars, “The approval of Trazimera, Pfizer’s first oncology biosimilar, is another significant step in our quest to introduce more treatment options for patients in Europe. Pfizer is investing in developing and launching a range of biosimilars which can help to reduce healthcare costs and increase patient access to important medicines.”
The EC approval is based on a comprehensive submission package which demonstrated a high degree of similarity for Trazimera and the originator product. The data included results from the REFLECTIONS B327-02 clinical comparative study, which showed clinical equivalence and found no clinically meaningful differences between Trazimera and originator product in patients with first-line HER2 overexpressing metastatic breast cancer.
Trazimera is Pfizer’s fourth biosimilar and the first oncology biosimilar to receive European approval. Pfizer’s biosimilars pipeline consists of nine distinct Pfizer and legacy Hospira biosimilar molecules in various stages of development.
Also in July, FDA approved the biosimilar Nivestym (filgrastim-aafi), a biosimilar to Neupogen (filgrastim). This is Pfizer’s fourth biosimilar to be approved by the FDA. Nivestym is approved for all eligible indications of the reference product.
“The FDA approval of Nivestym marks an important step in helping expand access to critical treatment options for patients with neutropenia, many of whom have cancer and can be hospitalized for potentially life-threatening side effects stemming from chemotherapy,” says Berk Gurdogan, U.S. Institutions president, Pfizer Essential Health. “We believe biosimilars, like Nivestym, are essential in helping to address evolving healthcare needs and may provide more affordable medicines to patients.”
The FDA approval was based on a review of a comprehensive data package and totality of evidence demonstrating a high degree of similarity of Nivestym compared to its reference product.
In the United States, Nivestym is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever; for reducing the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML); to reduce the duration of neutropenia and neutropenia-related clinical sequelae, e.g., febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation (BMT); and for the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis; for chronic administration to reduce the incidence and duration of sequelae of severe neutropenia (e.g., fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.
Nivestym was expected to be available in the United States at a significant discount to the current wholesale acquisition cost (WAC) of Neupogen. WAC is not inclusive of discounts to payers, providers, distributors, and other purchasing organizations.
In May, FDA approved Pfizer’s biosimilar Retracrit (epoetin alfa-epbx), the first U.S. biosimilar erythropoiesis-stimulating agent (ESA). Retacrit is a biosimilar to J&J’s Epogen and Procrit (epoetin alfa), and is approved for all indications of the reference product.
“As the first approved epoetin alfa biosimilar in the U.S., Retacrit may provide patients and their physicians with increased access to a high-quality, lower-cost alternative treatment option for anemia and the reduction of allogeneic red blood cell (RBC) transfusions in certain patients,” Gurdogan says. “We are proud of the progress of our biosimilars program to date, which will help address the evolving needs of patients and the broader healthcare community.”
FDA approval was based on a comprehensive data package submitted by Pfizer showing a high degree of similarity between Retacrit and the U.S. reference product, Epogen and Procrit.
In the United States, Retacrit is indicated for the treatment of anemia due to: chronic kidney disease (CKD) in patients on dialysis and not on dialysis; zidovudine in HIV-infected patients; the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy. Retacrit is also FDA-approved for the reduction of allogeneic red blood cell (RBC) transfusions in patients undergoing elective, noncardiac, nonvascular surgery.
“With the approval of Retacrit, healthcare providers now have an additional option to choose from when prescribing an ESA,” says George M. Rodgers, M.D., Ph.D., professor of Medicine, Division of Hematology and Hematologic Malignancies, Department of Internal Medicine, University of Utah School of Medicine. “By providing potentially more affordable therapeutic options, bio
similar medicines can allow for the reallocation of resources to other areas of cancer care. This is positive news for the oncology community.”
Retacrit is expected to be available in the United States at a significant discount to the current wholesaler acquisition cost of Epogen and Procrit.
Pfizer has entered into an agreement with Vifor Pharma Inc. for the commercialization of Retacrit in certain channels.
Outside of the biosimilars arena, Pfizer was granted FDA breakthrough therapy designation in September for the company’s 20-valent pneumococcal conjugate vaccine for the prevention of invasive disease and pneumonia in adults aged 18 years and older. Pfizer expected to start Phase III trials within a few months.
The FDA decision is informed by the results of the 20vPnC Phase II randomized, double-blind trial to evaluate the safety and immunogenicity of a multivalent pneumococcal conjugate vaccine in adults 60 through 64 years of age. Pfizer will seek to present and publish outcomes from this clinical trial at a future date.
“We look forward to continuing our dialogue with the FDA so that we can accelerate the development program of the adult indication of Pfizer’s 20-valent next-generation pneumococcal vaccine candidate,” says Kathrin U. Jansen, Ph.D., senior VP and head of Vaccine Research & Development, Pfizer. “There continues to be a global health need to protect against the potentially devastating effects of invasive pneumococcal disease and pneumonia caused by additional serotypes, and we are dedicated to continue to build on our expertise in pneumococcal conjugate vaccines with this vaccine candidate.”
The FDA previously granted fast track designation for 20vPnC in October 2017 for use in adults aged 18 years and older.
Pfizer continues to advance the company’s clinical collaborations in 2018. In September, the company disclosed data from a Phase II study that Bavencio (avelumab) plus Inlyta (axitinib) significantly improved progression-free survival in previously untreated patients with advanced renal cell carcinoma. This is the first positive Phase III immunotherapy trial in combination with a tyrosine kinase inhibitor (TKI) in any tumor type. The results were significant in both PDL1+ and all-comer populations.
Bavencio is from Merck KGaA and Inlyta is Pfizer’s drug. The companies announced positive top-line results from the pivotal Phase III JAVELIN Renal 101 study evaluating Bavencio in combination with Inlyta, compared with Sutent (sunitinib) as initial therapy for patients with advanced renal cell carcinoma (RCC). As part of a planned interim analysis, an independent Data Monitoring Committee confirmed that the trial showed a statistically significant improvement in progression-free survival (PFS) by central review for patients treated with the combination whose tumors had programmed death ligand-1 positive (PD-L1+) expression greater than 1 percent (primary objective), as well as in the entire study population regardless of PD-L1 tumor expression (secondary objective).
According to the statistical analysis plan, if PFS was statistically significant in the PD-L1+ subgroup, then PFS in the entire study population was to be analyzed for statistical significance. JAVELIN Renal 101 will continue as planned to the final analysis for the other primary endpoint of overall survival (OS). No new safety signals were observed, and adverse events for Bavencio, Inlyta, and Sutent in this trial were consistent with the known safety profiles for all three medicines.
Pfizer and Merck KGaA intend to pursue a regulatory submission in the United States based on these interim results, and these results will be discussed with global health authorities. A detailed analysis will also be submitted for presentation at an upcoming medical congress.
“JAVELIN Renal 101 is the first positive Phase III study combining an immune checkpoint blocker with a TKI, supporting the potential of Bavencio and Inlyta as a new cancer treatment approach for patients with advanced RCC,” says Chris Boshoff, M.D., Ph.D., senior VP and head of Immuno-Oncology, Early Development and Translational Oncology, Pfizer Global Product Development. “These positive results reinforce Pfizer’s long-standing heritage in advancing standards of care for people with RCC, and we look forward to discussing these data in greater detail with health authorities.”
In December 2017, FDA granted breakthrough therapy designation for Bavencio in combination with Inlyta for treatment-naïve patients with advanced RCC.
“We are encouraged by these data which illustrate the impact of Bavencio in combination with Inlyta as a potential first-line treatment for people with advanced RCC, a serious and life-threatening cancer,” says Luciano Rossetti, M.D., executive VP, global head of Research & Development at the Biopharma business of Merck KGaA, which operates in the United States and Canada as EMD Serono. “They also support our firm belief in the promise of combining Bavencio with currently approved therapies and novel agents, a strong focus of the overall JAVELIN clinical development program.”
JAVELIN Renal 101 is a global Phase III, multicenter, randomized (1:1) study investigating the efficacy and safety of Bavencio in combination with Inlyta as a first-line treatment option compared with Sutent monotherapy in 886 patients with advanced RCC across all risk groups. The primary objectives are to demonstrate that Bavencio in combination with Inlyta is superior to Sutent monotherapy in prolonging PFS or OS in patients with PD-L1+ tumors.
In July, Pfizer and Spark Therapeutics announced that Pfizer initiated a Phase III open-label, multi-center, lead-in study (NCT03587116) to evaluate the efficacy and safety of current factor IX prophylaxis replacement therapy in the usual care setting. The factor IX prophylaxis efficacy data obtained in the lead-in study will serve as the within-subject control group for those patients that enroll into the next part of the Phase III study, which will evaluate the investigational gene therapy fidanacogene elaparvovec for the treatment of hemophilia B. The interventional portion of this pivotal Phase III study will enroll patients who have completed at least six months in the lead-in study.
Fidanacogene elaparvovec is the official United States Adopted Name (USAN) and will become the Recommended International Nonproprietary Name (INN) for the therapy formerly known as SPK-9001 and PF-06838435.
The Phase III program was initiated following the transfer of the responsibility for Spark Therapeutics’ hemophilia B gene therapy program to Pfizer. Fidanacogene elaparvovec is a novel investigational vector that contains a bio-engineered adeno-associated virus (AAV) capsid (protein shell) and a high-activity human coagulation factor IX gene. The hope is that, once treated, patients will be able to produce factor IX themselves rather than having to regularly inject factor IX.
“With the lead-in study now open and actively recruiting patients, we are excited to begin our Phase III program evaluating fidanacogene elaparvovec for the treatment of hemophilia B,” says Brenda Cooperstone, M.D., aenior VP and chief development officer, Rare Disease, Pfizer Global Product Development. “The current data suggest immense promise for the use of this potential one-time treatment option. We look forward to the opportunity to continue the progress achieved by Spark Therapeutics for patients living with hemophilia B.”
In May 2018, Pfizer and Spark Therapeutics announced data for 15 participants in the ongoing Phase I/II clinical trial of fidanacogene elaparvovec for the treatment of severe or moderately severe (FIX:C < 2 percent) hemophilia B. The findings showed all 15 patients had discontinued routine infusions of factor IX concentrates with no reported serious adverse events or thrombotic events as of the May 7, 2018, data cutoff.
Pfizer and Spark Therapeutics entered into a License Agreement in December 2014 for the hemophilia B gene therapy program. Under the terms of the agreement, Pfizer will now assume sole responsibility for all subsequent pivotal studies, all regulatory activities, manufacturing and global commercialization of any products resulting from the hemophilia B gene therapy program.
Additionally during September, Pfizer received FDA breakthrough therapy designation for PF-06651600, an oral JAK3 inhibitor for treating alopecia areata. The chronic autoimmune skin disease causes hair loss on the scalp, face, or body.
The breakthrough therapy designation for alopecia areata was supported by positive results from a Phase II study, which was presented during the late-breaking news session at the 27th European Academy of Dermatology and Venerology (EADV) Congress in Paris on September 15, 2018. There are no FDA-approved treatments for alopecia areata, which impacts millions of people worldwide and is often associated with profound psychological consequences.
“We are encouraged by this breakthrough therapy designation as it underscores the potential of our JAK3 inhibitor to address a critical unmet need,” says Michael Corbo, chief development officer, Inflammation & Immunology, Pfizer Global Product Development. “We are continuing to work closely with the FDA on the development process with the goal of bringing this potential new treatment to patients living with alopecia areata as soon as possible.”
Pfizer is also working with the European Medicines Agency (EMA) on the clinical development program for PF-06651600.
Not all of the company’s clinical programs have advanced so well. In August, Pfizer announced that the company had terminated clinical studies for domagrozumab for the treatment of Duchenne muscular dystrophy. The studies were a Phase II safety and efficacy study (B5161002) and an open-label extension study (B5161004).
The Phase II study (B5161002), did not meet its primary efficacy endpoint, which was to demonstrate a difference in the mean change from baseline in 4 Stair Climb (in seconds) following one year of treatment with domagrozumab as compared to placebo in patients with DMD. Further evaluation of the totality of evidence including secondary endpoints did not support a significant treatment effect. The decision comes after a thorough review of data available at the time of the primary analysis, which evaluated all study participants after one year of treatment, as well as those participants who were in the trial beyond one year. The studies were not terminated for safety reasons.
“We are disappointed by these results and while we are not progressing with the studies, the data will contribute to a greater understanding of this disease and we will evaluate the total data set to see if there is a place for this medicine in muscular diseases,” says Seng Cheng, Ph.D., senior VP and chief scientific officer, Pfizer Rare Disease Research Unit. “We are extremely grateful to all those involved with this trial, especially the boys who participated, and their families.”
Pfizer is continuing research in DMD and rare neuromuscular diseases, with the goal of bringing therapies to patients with unmet needs. The company’s continued partnership with advocacy associations and the community is critical to finding innovative therapies for these diseases.
Pfizer has one ongoing clinical trial in DMD with a gene therapy, PF-06939926, which is an investigational, recombinant AAV9 capsid carrying a truncated or shortened version of the human dystrophin gene (mini-dystrophin) under the control of a human muscle specific promotor.
Commitment to U.S. advanced manufacturing
Pfizer is building a cutting-edge sterile injectable facility in Michigan, as announced in July. Pfizer is investing $465 million to build one of the most technically advanced sterile injectable pharmaceutical production facilities in the world in Portage, Mich. Management says this U.S. investment will strengthen Pfizer’s capability to produce and supply critical, life-saving injectable medicines for patients around the world.
Known as Modular Aseptic Processing (MAP), the new, multi-story, 400,000-square-foot production facility will also support the area economy by creating an estimated 450 new jobs over the next several years. This expands Pfizer’s presence in Portage, located in Kalamazoo County, where the company now employs more than 2,200 people at one of its largest plants.
“This investment is part of our overall plan announced in January to invest approximately $5 billion in U.S.-based capital projects as a result of the enactment of the Tax Cuts and Jobs Act,” Read says. “During the next six years, we expect to invest approximately $1.1 billion in Kalamazoo County – which is in addition to the $1 billion we have invested in the site over the past decade.”
Pfizer’s Portage site is a primary global supplier of sterile injectable, liquids and semi-solid medicines, and active pharmaceutical ingredients, producing more than 150 products. The leading product is Solu-Medrol, a widely used injectable anti-inflammatory medicine.
The plant has been in operation since 1948, and Pfizer has had a presence in the community through the legacy Upjohn Company since 1886. Pfizer’s operations in Kalamazoo County generate an estimated annual economic impact in west Michigan of $2.2 billion.