Amgen: New Business Cycle
Amgen is featuring an unprecedented collection of new product offerings, including the first-ever biosimilar cancer treatment to receive U.S. marketing clearance.
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All sales are in millions of dollars.
In millions of dollars, except EPS
According to Robert A. Bradway, chairman and chief executive officer of Amgen, “Importantly, through 2016, we remained squarely on track with our long-term strategy for growth and, in particular, on our trajectory to meet or exceed the 2018 commitments we made to shareholders back in 2014.”
Bradway says 2016 was a year in which Amgen started a necessary pivot into a new business cycle, one featuring branded and non-branded competition for some of the company’s medicines and an unprecedented set of new product offerings. Amgen achieved 94 product/country approvals during 2016, and many of them brought significant new medicines to undeserved geographies.
“The strength of our product portfolio reflected in 6 percent revenue growth in 2016, to a record $23 billion,” Bradway notes. “The company-wide transformation efforts that we proactively began four years ago continued to bear fruit, helping us to achieve 12 percent non-GAAP earnings per share growth and a 52 percent non-GAAP operating margin in 2016, demonstrating our commitment to operational excellence.”
As part of the company’s core strategy, Amgen develops innovative products in six concentrated therapeutic areas: cardiovascular disease, oncology, bone health, neuroscience, nephrology, and inflammation. During 2016, Amgen continued to build on the momentum from the company’s unprecedented series of new product approvals and launches that started in 2015, according to Bradway. “The rapid pace of market introductions included six innovative medicines that address important medical needs: Repatha (evolocumab), Kyprolis (carfilzomib), Blincyto (blinatumomab), Imlygic (talimogene laherparepvec), the Neulasta (pegfilgrastim) Onpro kit and Corlanor (ivabradine). Repatha and Kyprolis represent especially significant opportunities due to the impact of the diseases they address and treat and the important therapeutic benefits they provide.”
Amgen was recently fueled by a milestone biosimilar approval from the U.S. Food and Drug Administration, for a cancer drug jointly developed with Allergan. The generic biological drug MVASI was approved for a wide range of cancer indications as the biosimilar version to Roche/Genentech’s blockbuster Avastin, which generated 2016 sales of about $6.89 billion.
According to company management, novel mechanisms and first-in-class therapies feature prominently across Amgen’s pipeline. These products include omecamtiv mecarbil, a novel cardiac myosin activator being developed in collaboration with Cytikinetics for treating chronic heart failure; the anti-sclerostin monoclonal antibody EVENITY (romosozumab) being developed with partner UCB for osteoporosis treatment; and the small molecule inhibitor of beta secretase (BACE) CNP520/AMG 520, which is undergoing joint development with
Novartis for the prevention of Alzheimer’s disease. BACE is an enzyme that contributes to the buildup of amyloid plaque in the brains of Alzheimer’s patients.
“This is an exciting time for Amgen and biotechnology,” Bradway explains. “Innovation is flourishing, with innovative medicines making a difference in the fight against previously intractable diseases. Excitement and momentum are palpable at Amgen as we mine advances in our understanding of human genetics to identify high-potential biological targets, build next-generation biomanufacturing platforms and continue transforming our business in ways that increase our agility, speed and competitiveness. With the emergence of significant new insights and technologies, we are witnessing an unprecedented number of opportunities to address serious illness in important new ways.”
Amgen reported 2017 first-half revenue of $11.27 billion, compared to $11.22 billion during the 2016 corresponding time frame. Growth of 1 percent in worldwide product sales for the six-month period ended June 30, 2017, was driven primarily by Prolia (denosumab), Sensipar/Mimpara (cinacalcet), Repatha, and Kyprolis.
First-half net income for 2017 amounted to $4.22 billion versus $3.77 billion during the first six months of the previous calendar term. Diluted earnings per share increased from $4.97 in the first six months of 2016 to $5.71 for the first two quarters of 2017. On the other hand, R&D decreased from $1.77 billion in first-half 2016 to $1.64 billion for the first six months of 2017.
Based on the first-half performance, full-year 2017 EPS guidance increased to $10.79-$11.37 on a GAAP basis and $12.15-$12.65 on a non-GAAP basis. Additionally, total revenues guidance for 2017 was revised by Amgen to $22.5-$23.0 billion.
Enbrel (etanercept) remains Amgen’s top-selling product, with 2016 worldwide sales of almost $6 billion and first-half 2017 sales of $2.65 billion. Enbrel global sales were down 1 percent in first-half 2017, with the decrease driven primarily by the impact of competition.
Launched during 1998, Enbrel is used primarily in indications for treating adult patients with moderately to severely active rheumatoid arthritis, chronic moderate-to-severe plaque psoriasis patients who are candidates for systemic therapy or phototherapy, and active psoriatic arthritis.
Though slowly trending downward, Neulasta remains Amgen’s second-best seller with 2016 global sales of almost $4.65 billion and a first-half 2017 total of nearly $2.3 billion. The worldwide Neulasta sales decline for the six-month period ended June 30, 2017, was driven primarily by a decrease in unit demand, offset partially by favorable changes in accounting estimates. Use of the Neulasta Onpro kit continued to grow in the United States.
Introduced to the marketplace in 2002, Neulasta is a pegylated protein based on the filgrastim molecule. The product is available to help reduce the chance of infection due to a low white blood cell count, in people with certain types of cancer (nonmyeloid) who receive anti-cancer medicines (chemotherapy) that can cause fever and a low blood cell count. During 2015, the Neulasta Onpro kit became available in the United States.
Amgen’s No. 3 seller Aranesp (darbepoetin alfa) generated $2.09 billion during 2016 and almost $1.05 billion for the 2017 first half. The product’s global first-half 2017 sales increased due primarily by higher unit demand, including a shift by some U.S. dialysis customers from Epogen (epoetin alfa) to Aranesp, offset partially by unfavorable changes in foreign exchange rates. According to Amgen, Aranesp may face short-acting competition from a proposed biosimilar in the United States.
Aranesp was launched during 2001 and is indicated to treat a lower-than-normal amount of red blood cells (anemia) caused by CKD (in both patients on dialysis and patients not on dialysis). The product is additionally indicated for treating anemia due to concomitant myelosuppressive chemotherapy in patients with non-myeloid malignancies, and when chemotherapy will be used for at least two months after starting Aranesp.
Following Aranesp on the Amgen sales ladder is Prolia, which produced about $1.64 billion for 2016 and $930 million during the first six months of 2017. The double-digit sales increase in first-half 2017 was driven primarily by higher unit demand.
A RANK ligand (RANKL) inhibitor, Prolia was launched in the United States and Europe in 2010. Prolia is approved by the FDA for the treatment of postmenopausal women with osteoporosis at high risk for fracture; for treatment to increase bone mass in men with osteoporosis at high risk for fracture; as a treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer; and as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer. In Europe, the product is used primarily for treating osteoporosis in postmenopausal women at increased risk of fracture.
Another blockbuster brand for Amgen is Sensipar/Mimpara, with sales growing to $1.58 billion for 2016 and $848 million for the 2017 first half. Sensipar/Mimpara global sales for the three-month and six-month periods ended June 30, 2017, were driven primarily by an increase in net selling price. The U.S. composition of matter patent relating to the small molecule Sensipar expires during March 2018. Amgen says the company is also involved in a number of litigation matters related to Sensipar.
Sensipar is the first oral calcimimetic agent approved by the FDA for treating secondary hyperparathyroidism (HPT) in adult patients with CKD on dialysis. The therapy is also FDA-approved for treating hypercalcemia in adult patients with parathyroid carcinoma and hypercalcemia in adult patients with primary HPT for whom parathyroidectomy would be indicated on the basis of serum calcium levels, but who are unable to undergo parathyroidectomy.
Mimpara was initially approved in the EU during 2004 and is the first oral calcimimetic agent cleared by the EC for treating secondary HPT in patients with ESRD on maintenance dialysis therapy. The therapy is additionally approved in the EU for reducing hypercalcemia in adult patients with parathyroid carcinoma and with primary HPT for whom parathyroidectomy would be indicated on the basis of serum calcium levels (as defined by relevant treatment guidelines), but in whom parathyroidectomy is not clinically appropriate or is contraindicated.
Sensipar/Mimpara binds to the calcium-sensing receptor, resulting in a drop in PTH levels by inhibiting PTH synthesis and secretion. The reductions in PTH also lower serum calcium and phosphorus levels.
XGEVA (denosumab) sales rose to almost $1.53 billion in 2016 and to $797 million for the first six months of 2017. According to Amgen, increased global XGEVA sales for Q2 and H1 2017 were driven primarily by higher unit demand.
XGEVA is the first fully human monoclonal antibody that binds to and neutralizes RANKL – a protein essential for the formation, function and survival of osteoclasts, which break down bone – thereby inhibiting osteoclast-mediated bone destruction.
XGEVA was introduced in the United States in 2010. The product is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors and is the No. 1 prescribed agent by oncologists for this indication in the United States. XGEVA is additionally indicated for treating adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity. The medicine is also approved by the FDA for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.
XGEVA was launched in Europe in 2011 and is used primarily in the indication for the prevention of SREs in adults with bone metastases from solid tumors.
Rounding out Amgen’s blockbuster medicine portfolio is Epogen, which produced 2016 sales of $1.28 billion and a first-half 2017 performance of $562 million. The 2017 sales decline was driven primarily by a decrease in net selling price due to a negotiated contract with DaVita. Multiple companies are developing proposed biosimilar versions of Epogen, with one of them having received a Complete Response Letter from the FDA regarding its approval application.
Introduced to the market in 1989, Epogen is indicated for treating anemia due to chronic kidney disease in patients on dialysis to decrease the need for red blood cell (RBC) transfusion.
Like Epogen, Neupogen (filgrastim) is another long-running market success for Amgen that is on the downside of its career in terms of sales production. Neupogen sales totaled $765 million for 2016, down by $284 million compared to its prior-year amount. The sales decline continued during first-half 2017, with a drop-off to $285 million versus $409 million during the 2016 first-half period.
Neupogen is a recombinant-methionyl human granulocyte colony-stimulating factor (G-CSF) that was launched during 1991. The product helps reduce the chance of infection due to a low white blood cell count in people with certain types of cancer (non-myeloid) who receive anti-cancer medicines (chemotherapy) that can cause fever and a low blood cell count.
Kyprolis sales reached $692 million during 2016 and the product’s upward growth trajectory continued in first-half 2017, amounting to $401 million, driven by its ROW performance.
Kyprolis is marketed around the globe, including in the United States in combination with dexamethasone or with lenalidomide plus dexamethasone for treating patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy, and as a single agent for treating patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.
Kyprolis has been demonstrated to block proteasomes – which play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed – leading to an excessive build-up of proteins within cells. In some cells, Kyprolis can cause cell death, especially in myeloma cells because they are more likely to contain a higher level of abnormal proteins.
Vectibix (panitumumab) sales improved from $549 million in 2015 to $611 million in 2016, and the drug’s 2017 first-half sum came in at $315 million. Vectibix is the first fully human monoclonal anti-EGFR antibody to gain FDA approval for treating metastatic colorectal cancer (mCRC). The product was approved in the United States during September 2006 as a monotherapy for treating patients with EGFR-expressing mCRC after disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy.
The FDA approved Vectibix during May 2014 for use in combination with FOLFOX as first-line treatment in patients with wild-type KRAS (exon 2) mCRC. With this marketing clearance, Vectibix became the first biologic therapy indicated for use with FOLFOX, one of the most commonly used chemotherapy regimens, in the first-line treatment of mCRC for patients with wild-type KRAS mCRC.
Nplate (romiplostim) global sales amounted to $584 million during 2016 and $318 million for first-half 2017. For the 2017 period, U.S. sales improved 15 percent to $196 million and ROW sales climbed up 8 percent to $122 million.
Nplate is approved in more than 50 countries. The thrombopoietin receptor agonist is the first FDA-approved treatment specifically for adult chronic immune thrombocytopenia (ITP). Nplate was approved in the EU during February 2009 for treating adult chronic-immune (idiopathic)-thrombocytopenic-purpura patients refractory to other treatments such as corticosteroids and immunoglobulins. Nplate received orphan designation for chronic ITP in the United States (2003), the EU (2005) and other parts of the world.
Repatha worldwide sales for first-half 2017 amounted to $132 million compared to $43 million during the corresponding 2016 period. The human monoclonal antibody inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). Repatha binds to PCSK9 and inhibits circulating PCSK9 from binding to the low-density lipoprotein (LDL) receptor (LDLR), preventing PCSK9-mediated LDLR degradation and allowing LDLR to recycle back to the liver cell surface. By inhibiting the binding of PCSK9 to LDLR, Repatha increases the amount of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels.
Repatha is approved in more than 50 countries including the United States, Japan, Canada and in all 28 EU member countries. Applications in other countries are under evaluation.
“Amgen’s portfolio of 10 biosimilars in development represents a substantial opportunity, with global 2016 originator sales for these products exceeding $60 billion,” Bradway says. During September the U.S. FDA approved one of those biosimilars, MVASI (bevacizumab-awwb), for all eligible indications of the reference product Avastin.
MVASI is the first anti-cancer biosimilar, as well as the first bevacizumab biosimilar, to gain FDA marketing clearance. MVASI won approval for treating five types of cancer: in combination with chemotherapy for non-squamous non-small cell lung cancer (NSCLC), in combination with chemotherapy for mCRC, glioblastoma, metastatic renal cell carcinoma in combination with interferon alfa and in combination with chemotherapy for persistent, recurrent, or metastatic carcinoma of the cervix.
MVASI is the first product from Amgen’s collaboration with Allergan to gain U.S. marketing approval. During December 2011, Amgen and Allergan (then Watson Pharmaceuticals) formed a collaboration to develop and commercialize, on a global basis, four oncology antibody biosimilar medicines. Amgen assumes primary responsibility for developing, manufacturing and initially commercializing the oncology antibody products.
Amgen and Allergan’s bevacizumab biosimilar is also undergoing review by the European Medicines Agency, following a Marketing Authorization Application filed in December 2016.
Bevacizumab is a recombinant immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to vascular endothelial growth factor (VEGF) and inhibits the interaction of VEGF with its receptors, VEGF receptor-1 and VEGF receptor-2, thus inhibiting establishment of new blood vessels necessary for the maintenance and growth of solid tumors.
Amgen and Allergan filed a Marketing Authorization Application to the EMA during March and a Biologics License Application to the FDA in July for ABP 980. ABP 980 is the second of four oncology biosimilar medicines from the Amgen and Allergan collaboration to be filed for FDA approval.
Amgen and Allergan announced during September data from a Phase 3 study trial assessing the efficacy and safety of the biosimilar ABP 980 compared with the originator product Herceptin (trastuzumab) in patients with human epidermal growth factor receptor 2-positive (HER2-positive) early breast cancer. According to Amgen, efficacy, safety and immunogenicity data support ABP 980 as a trastuzumab biosimilar and add to the totality of evidence under review by the EMA and FDA.
Trastuzumab is marketed by Roche/Genentech as Herceptin, one of the world’s best-selling medicines. The recombinant DNA-derived humanized monoclonal immunoglobulin G1 kappa antibody is approved in many regions for the treatment of HER2-overexpressing early breast cancer, adjuvant breast cancer, metastatic breast cancer and metastatic gastric cancer.
The European Commission during March granted marketing authorization for Amgevita (biosimilar adalimumab) in all available indications, marking Amgen’s first biosimilar approval in the EU. This regulatory clearance also marked the first biosimilar adalimumab approved in the European Union. Adalimumab is the active ingredient in the world’s best-selling prescription medicine Humira, an anti-TNF-α monoclonal antibody.
Amgevita is authorized for treating certain inflammatory diseases in adults, including moderate-to-severe rheumatoid arthritis; psoriatic arthritis; severe active ankylosing spondylitis (AS); severe axial spondyloarthritis without radiographic evidence of AS; moderate-to-severe chronic plaque psoriasis; moderate-to-severe hidradenitis suppurativa; non-infectious intermediate, posterior and panuveitis; moderate-to-severe Crohn’s disease and moderate-to-severe ulcerative colitis. The European Commission additionally approved Amgen’s biosimilar adalimumab for treating certain pediatric inflammatory diseases, including moderate-to-severe Crohn’s disease (ages 6 years and older), severe chronic plaque psoriasis (ages 4 years and older), enthesitis-related arthritis (ages 6 years and older) and polyarticular juvenile idiopathic arthritis (ages 2 years and older).
Biosimilar adalimumab garnered FDA marketing clearance on Sept. 23, 2016, under the brand name Amjevita (adalimumab-atto).
Amgen revealed in September new analysis of the cardiovascular outcomes study FOURIER (Further Cardiovascular OUtcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) showing that lowering low-density lipoprotein cholesterol (LDL-C) levels with Repatha significantly and consistently reduced cardiovascular events in patients with and without diabetes at baseline.
A new analysis was announced by Amgen in August demonstrating that lowering LDL-C levels with Repatha reduced the risk of cardiovascular events in a sub-group of patients with a history of stroke from FOURIER. No new safety concerns were identified in this cohort of over 5,000 patients.
The FDA granted priority review for Amgen’s supplemental Biologics License Application for Repatha in July. If approved for marketing, the U.S. prescribing information for Repatha will be updated to include risk reduction of major cardiovascular events based on data from FOURIER. FDA regulators set a Prescription Drug User Fee Act (PDUFA) action date of Dec. 2, 2017. In June, Amgen announced the filing of the sBLA with FDA and a variation to the marketing authorization to the EMA to include data from the 27,564-patient Phase 3 Repatha cardiovascular outcomes study.
Repatha gained European Commission approval during February for a new 420-mg single-dose delivery option. The automated mini-doser (AMD) with a pre-filled cartridge is a hands-free device providing 420 milligrams of Repatha in one injection per administration. Repatha is the first proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor in Europe with a single monthly injection option.
In other September news, Amgen and UCB – the global collaboration partner in the development of EVENITY – announced detailed results from the Phase 3 ARCH (ActivecontRolled FraCture Study in Postmenopausal Women with Osteoporosis at High Risk of Fracture) study. The clinical trial demonstrated that 12 months of EVENITY followed by alendronate was superior in reducing new vertebral, clinical, non-vertebral and hip fracture risk in postmenopausal women with osteoporosis at high risk for fracture, versus alendronate alone. These results were published in the New England Journal of Medicine.
During July, Amgen and UCB announced that the FDA issued a Complete Response Letter for the BLA for EVENITY as a treatment for postmenopausal women with osteoporosis. The resubmission will include data from ARCH and the Phase 3 BRIDGE (placeBo-contRolled study evaluatIng the efficacy anD safety of romosozumab in treatinG mEn with osteoporosis) trial evaluating EVENITY in men with osteoporosis, in addition to the Phase 3 FRAME (FRActure study in postmenopausal woMen with ostEoporosis) study. As a result, FDA marketing approval of EVENITY is not expected to take place during 2017.
Aimovig (erenumab) is being developed as the first investigational biologic product specifically designed to prevent migraine by blocking the calcitonin gene-related peptide (CGRP) receptor, which is associated with migraine activation. A Biologics License Application for Aimovig was accepted for review by the FDA in July – with a PDUFA target action date of May 17, 2018 – for the prevention of migraine in patients experiencing four or more migraine days per month. If approved, Aimovig is expected to be the first monoclonal antibody targeting the CGRP receptor, specifically designed for the prevention of migraine.
Aimovig has been studied in several large worldwide, randomized, double-blind, placebo-controlled trials to assess its safety and efficacy in migraine prevention. More than 2,600 patients have been exposed to Aimovig across the four placebo-controlled Phase 2 and Phase 3 clinical trials and their open-label extension. Aimovig is being developed and commercialized jointly with Novartis.
At the end of August, the European Commission granted Marketing Authorization of a pediatric formulation (granules in capsule for opening) of Mimpara for treating secondary hyperparathyroidism in children 3 years and older with end‑stage renal disease on maintenance dialysis therapy in whom secondary HPT is not adequately controlled with standard of care therapy.
Amgen reported on Aug. 30 that the FDA accepted for review a supplemental New Drug Application based on the overall survival data from the Phase 3 head-to-head ENDEAVOR study showing that Kyprolis and dexamethasone (Kd) reduced the risk of death by 21 percent and increased OS by 7.6 months compared to Velcade (bortezomib) and dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma. The U.S. regulatory agency set a PDUFA action date of April 30, 2018 for the sNDA application, which was submitted in July. Also during August, Amgen announced a variation to the marketing application to the EMA to include overall survival data from the Phase 3 head-to-head ENDEAVOR trial in the product label.
A supplemental Biologics License Application was filed with the FDA in July for Prolia as a treatment for patients with glucocorticoid-induced osteoporosis (GIOP). The sBLA is based on a Phase 3 trial assessing the safety and efficacy of Prolia compared with risedronate in patients receiving glucocorticoid treatment.
The FDA approved the sBLA for Blincyto in July to include overall survival data from the Phase 3 TOWER trial, converting an accelerated approval to a full approval. The marketing clearance expands the product’s indication for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) in adults and children. The bispecific CD19-directed CD3 T cell engager (BiTE) antibody construct Blincyto binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.
Blincyto was granted breakthrough therapy and priority review designations by the FDA, and was initially approved in the United States in December 2014 as the first BiTE Immunotherapy. During November 2015, Blincyto was granted conditional marketing authorization in the EU for treating adults with Ph- relapsed or refractory B-cell precursor ALL. Other regulatory applications for Blincyto have been filed with health authorities worldwide.
The FDA in June accepted the XGEVA sBLA seeking to expand the current approved indication for the prevention of fractures and other skeletal-related events in patients with bone metastases from solid tumors to include patients with multiple myeloma. The U.S. regulatory agency scheduled a PDUFA target action date of Feb. 3, 2018.
Amgen’s Parsabiv (etelcalcetide) was cleared for marketing by the FDA in February as a treatment for secondary hyperparathyroidism in adult patients with chronic kidney disease on hemodialysis. Parsabiv became the first therapy approved for this condition in 12 years and the only calcimimetic that can be administered intravenously by the dialysis health-care team three times a week at the end of the hemodialysis session.