Amgen: The Next Generation
One Amgen Center Drive
Thousand Oaks, CA
|Product||2014 Sales||2013 Sales|
All sales are in millions of dollars.
In millions of dollars, except EPS
Recognized in the 2014 edition of this special report as Med Ad News’ Company of the Year, Amgen continues to thrive and pace the biotech marketplace by way of successful brands, rewarding M&A activity and international expansion. In addition, Amgen is developing a pipeline of innovative prescription products with breakaway potential while also advancing its portfolio of biosimilar medicines.
For Amgen, 2015 marks the 35th anniversary of business operations. Since 1980, Amgen has grown to become a leading independent biotech force. Based out of Thousand Oaks, Calif., Amgen primarily markets recombinant protein therapeutics for supportive cancer care, inflammation, nephrology and bone health.
Amgen is undergoing a significant transformation designed to position the company to deliver long-term, industry-leading innovation and financial returns. To that end, during second-half 2014 Amgen initiated a restructuring plan to invest in continuing innovation and the launch of the company’s new pipeline molecules while improving its cost structure. As part of the plan, Amgen would reduce its staff by 3,500 to 4,000 by year-end 2015, close facilities in Washington state and Colorado, and reduce the amount of buildings at headquarters in Thousand Oaks.
Amgen expects that these actions will result in pre-tax accounting charges in the range of $935 million to $1.04 billion, of which $650 million was incurred through March 31, 2015. During the three-month period ended March 31, 2015, Amgen incurred $92 million of restructuring costs. Management expected that substantially all remaining restructuring actions and related estimated costs would be incurred during the rest of 2015 to support the company’s transformation and process improvement efforts. Net savings are not expected to be significant during 2015 because of investments in new product launches and external business development.
Managers say Amgen is positioned well for future sustainable growth. According to leadership, Amgen’s focus, expense discipline and priorities are clear: successfully execute on new product launches; grow key products, including Enbrel, Prolia, XGEVA, Vectibix, Sensipar and Nplate; advance the company’s robust pipeline of important medicines; transform the business to increase agility and deliver efficiencies and cost savings across the company; and continue to deliver progress against long-term objectives.
A significant milestone was attained during 2014 when the company debuted its next-generation biomanufacturing plant in Singapore. The site was built in less than two years and completed in half the time required for conventional manufacturing facilities. Management anticipates starting production of Amgen’s first commercial products in Singapore during 2017.
Also on the international front during 2014, Amgen continued to expand into new markets in Latin America, the Middle East, and Asia. Amgen leadership anticipates $2 billion in sales from the company’s worldwide expansion efforts by 2018.
2014 marked the first year that Amgen topped $20 billion in annual sales. Compared to 2013, Amgen total revenue grew 7 percent year-over-year to $20.06 billion, with 6 percent product sales growth spurred by strong performance across the portfolio. Adjusted operating income advanced 22 percent to $8.48 billion versus the 2013 result. Adjusted EPS rose 14 percent to $8.70, driven by higher operating income offset partially by a higher tax rate in 2014.
R&D expenses increased 5 percent compared to 2013 for a total of $4.3 billion, paced by the addition of Onyx Pharmaceuticals’ programs and support for later-stage clinical programs, offset partially by reduced expenses associated with marketed product support and Discovery Research & Translational Sciences. During 2013 Amgen acquired Onyx, a leading biopharma company with innovative medicines that further strengthened Amgen’s oncology business.
Amgen revenue for the first half of 2015 totaled $10.4 billion compared to $9.7 billion during the one-year-earlier period. Net income improved from $2.62 billion in the first two quarters of 2014 to $3.28 billion for the first six months of 2015, and diluted EPS also rose, from $3.41 to $4.26. R&D expenses during January-June 2015 came to $1.86 billion, down from $2.05 billion in first-half 2014.
Amgen’s full-year 2015 revenue and EPS guidance was upgraded based on the first-half performance. Revenue guidance grew from $20.9 billion-$21.3 billion to $21.1 billion-$21.4 billion. Adjusted earnings per share were raised from $9.35-$9.65 to $9.55-$9.80.
For 2014, Amgen’s top seven product lines accounted for 93 percent of the company’s $19.3 billion in medicine sales, compared to $18.2 billion in 2013 registered by the same drug franchises. Seventy-six percent of 2014 product sales were generated in the United States.
Heading 2014 sales for Amgen was Enbrel (etanercept), which was launched during 1998. The medicine is used primarily 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. Amgen markets Enbrel primarily in the United States, and the rights to market and sell the medicine outside the United States and Canada belong to Pfizer Inc.
Combined Enbrel sales for Amgen, Pfizer and Takeda Pharmaceutical Co. placed the drug at No. 4 amongst all prescription medicines during 2014 at about $8.88 billion. For Amgen, Enbrel sales grew from $4.24 billion in 2012 to $4.55 billion during 2013 to $4.69 billion for 2014. The anti-TNF agent produced first-half 2015 sales for Amgen of $2.46 billion.
Also leading the company’s sales charge is Neulasta, a pegylated protein based on the filgrastim molecule, marketed mainly in the United States and Europe. The drug was introduced to the marketplace during 2002 and is indicated to decrease the incidence of infection associated with chemotherapy-induced febrile neutropenia in cancer patients with non-myeloid malignancies. In December 2014, U.S. regulators granted approval clearance for the Neulasta Delivery Kit, including the On-body Injector for Neulasta.
For calendar-year 2014, Neulasta global sales for Amgen totaled $4.6 billion, representing a 5 percent increase versus the 2013 tally. Neulasta remained Amgen’s No. 2 best seller during first-half 2015 with a total of $2.29 billion.
Amgen markets the active chemical denosumab in the United States and Europe under the brand names XGEVA and Prolia for different indications, patient populations, doses, and frequencies of administration. Launched in the United States during 2010, XGEVA is used for the prevention of skeletal-related events (SREs) (pathological fracture, radiation to bone, spinal cord compression or surgery to bone) in patients with bone metastases from solid tumors. The drug was introduced in Europe during 2011.
XGEVA received U.S. regulatory clearance during December 2014 for treating hypercalcemia of malignancy refractory to bisphosphonate therapy.
XGEVA sales advanced 20 percent from $1.02 billion during 2013 to $1.22 billion for 2014. For the January-June 2015 period, the drug’s sales reached $671 million.
Prolia made its market debut in the United States and Europe during 2010. In the United States, Prolia is intended for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. In Europe, Prolia is used primarily for the treatment of osteoporosis in postmenopausal women at increased risk of fractures.
Prolia sales have been growing rapidly, reaching blockbuster status during 2014 at $1.03 billion, up 38 percent from the 2013 amount of $744 million. Sales for the first six months of 2015 came in at $612 million.
Amgen markets a pair of erythropoiesis-stimulating agents: Epogen (epoetin alfa) and Aranesp (darbepoetin alfa). Epogen was introduced in the United States in 1989 for dialysis patients. The drug treats a lower-than-normal number of red blood cells (anemia) caused by chronic kidney disease in patients on dialysis to lessen the need for red blood cell transfusions.
Despite its long-running market presence, Epogen annual sales continue to rise. The product generated $1.94 billion during 2012, $1.95 billion in 2013, and $2.03 billion for 2014. The sales improvement continued during first-quarter 2015 with a 16 percent increase year-over-year, but the second-quarter 2015 performance was down 4 percent versus Q2 2014, with a first-half 2015 total of $1.03 billion.
Aranesp, which is marketed by Amgen primarily in Europe and in the United States, was launched during 2001. The product is indicated for treating anemia associated with chronic kidney disease (in both patients on dialysis and patients not on dialysis) and treating anemia due to concomitant myelosuppressive chemotherapy in patients with non-myeloid malignancies.
Aranesp sales have held fairly steady during the past two calendar years, increasing from $1.91 billion in 2013 to $1.93 billion during 2014. The medicine’s sales for second-half 2015 came in at $959 million.
The recombinant methionyl human granulocyte colony-stimulating factor (G-CSF) Neupogen is marketed by Amgen primarily in the United States, Canada and Europe. Introduced in 1991, Neupogen is used for reducing the incidence of infection as manifested by febrile neutropenia for patients with non-myeloid malignancies undergoing myelosuppressive chemotherapy associated with a significant incidence of severe neutropenia with fever.
Neupogen sales for 2014 declined 17 percent from the 2013 total, coming in at $1.16 billion. For the first two quarterly periods of 2015, Neupogen sales registered at $502 million.
Amgen markets the chemical ingredient cinacalcet as Sensipar in the United States and as Mimpara in Europe. Introduced in 2004, the drug is used for the treatment of secondary hyperparathyroidism in chronic kidney disease patients on dialysis.
Sales for Sensipar/Mimpara grew from $950 million during 2012 to $1.09 billion for 2013 to $1.16 billion in 2014. Sensipar/Mimpara sales for first-half 2015 amounted to $678 million.
Approval of a game-changing cholesterol reducer
Amgen and various industry insiders are very excited about the market arrival of Repatha for lowering “bad” cholesterol. The anticipated blockbuster brand was approved by the U.S. Food and Drug Administration on Aug. 27, 2015. Amgen submitted the biologics license application (BLA) to the FDA for Repatha as a treatment of high cholesterol during November 2014.
The new drug is indicated in the United States as an adjunct to diet and maximally tolerated statin therapy for treating adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD), who require additional lowering of low-density lipoprotein cholesterol (LDL-C); and as an adjunct to diet and other LDL-lowering therapies for the treatment of patients with homozygous familial hypercholesterolemia (HoFH), who require additional lowering of LDL cholesterol.
During July 2015, Repatha became the first PCSK9 inhibitor approved anywhere worldwide when the European Commission granted marketing authorization. Repatha was approved for treating adults with primary hypercholesterolemia or mixed dyslipidemia, as an adjunct to diet in combination with a statin or statin with other lipid-lowering therapies in patients unable to reach LDL-C goals with the maximum tolerated dose of a statin, or alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or from whom a statin is contraindicated; and as a treatment of adults and adolescents aged 12 years and over with homozygous familial hypercholesterolemia in combination with other lipid-lowering therapies.
Repatha was filed for regulatory approval in Japan during March 2015 for treating high cholesterol. The medicine is being developed in Japan by Amgen Astellas BioPharma K.K., a joint venture between Amgen and another Med Ad News top 50 company, Tokyo-based Astellas Pharma Inc.
Containing the active ingredient evolocumab, Repatha is a human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9. The drug binds to PCSK9 and inhibits circulating PCSK9 from binding to the low-density lipoprotein receptor (LDLR). This process prevents PCSK9-mediated LDLR degradation and enables 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.
On Sept. 11, 2015, Amgen announced the submission of an application to FDA for marketing clearance of a single-dosing option for the monthly administration of Repatha Injection. The additional approval would allow for a 420-mg monthly dose to be administered as a single injection. Repatha is already available as a single-use 140 mg/mL prefilled SureClick autoinjector or prefilled syringe that patients can self-administer at the recommended dose for adults of 140 mg every two weeks or 420 mg once per month. For patients with HoFH, the recommended dose is 420 mg once every month.
Phase III trials are under way to investigate Repatha for cardiovascular outcomes, on cognitive function, in statin-intolerant subjects, in subjects with genetic low-density lipoprotein disorders, and with intravascular ultrasound.
GLAGOV, the intravascular ultrasound study, is determining the effect of Repatha on coronary atherosclerosis in 950 patients undergoing cardiac catheterization to test the hypothesis of robust LDL-C reduction leading to a reduction or a change in the build-up of plaque in the arteries. Results from the GLAGOV study are anticipated by Amgen during 2016.
The FOURIER outcomes study is designed to evaluate whether treatment with Repatha in combination with statin therapy versus placebo plus statin therapy reduces the risk of recurrent cardiovascular events in patients with high cholesterol and clinically evident cardiovascular disease. Patient enrollment was completed during June 2015. Results from the 27,500-patient FOURIER trial are expected no later than 2017 (event-driven).
Recent product approvals/launches and pipeline updates
Blincyto (blinatumomab) is a new option in Amgen’s medicine cabinet. The product was cleared for marketing by U.S. regulators during December 2014 for relapsed/refractory acute lymphoblastic leukemia (ALL). The drug was approved by FDA less than three months after submission. According to Amgen, Blincyto is an important new treatment option for patients and serves as proof of concept for the company’s BiTE technology platform in the potential treatment of other cancers.
Blincyto is the first bispecific CD19-directed CD3 T cell engager (BiTE) antibody construct product as well as the first single-agent immunotherapy to be FDA-approved for treating patients with Philadelphia chromosome-negative (Ph) relapsed or refractory B-cell precursor ALL, a rare and rapidly progressing cancer of the blood and bone marrow. Before marketing approval, Blincyto was granted breakthrough therapy and priority review designations by the FDA.
On the clinical front, Amgen reported in July 2015 that Blincyto showed clinical activity in a Phase II trial in patients with relapsed/refractory Philadelphia chromosome positive B-cell precursor acute lymphoblastic leukemia. The investigational study demonstrated that blinatumomab monotherapy induced a complete remission or complete remission with partial hematological recovery within two cycles of treatment in a clinically meaningful amount of patients.
Amgen officials said the product’s launch has made solid progress. The company reported U.S. sales for Blincyto of $3 million for December 2014 and $15 million during first-quarter 2015.
Amgen established its cardiovascular presence in the United States during April 2015 when the company was granted marketing clearance for Corlanor (ivabradine). The drug was approved to reduce the risk of hospitalization for worsening heart failure in patients with stable, symptomatic chronic heart failure with left ventricular ejection fraction ≤35 percent, who are in sinus rhythm with resting heart rate ≥70 beats per minute and either are on maximally tolerated doses of beta blockers or have a contraindication to beta blocker use. Corlanor was introduced to the U.S. market during April 2015. Corlanor is the first new medicine approved for chronic heart failure in the United States in almost a decade.
The Neulasta Delivery Kit was made available in the United States during March 2015. The Neulasta Delivery Kit contains a specially designed single-use prefilled syringe co-packaged with the new On-body Injector for Neulasta. The Neulasta Delivery Kit allows for a healthcare provider to initiate administration of the medicine on the same day as cytotoxic chemotherapy – with delivery of the patient’s full dose of Neulasta the day after chemotherapy administration. This allows patients to avoid a return visit to their physician the day after chemotherapy.
Results from a Phase I pharmacokinetic study showed that the On-body Injector for Neulasta offers comparable pharmacokinetics to the drug delivered through the prefilled syringe for manual use.
The leukocyte growth factor Neulasta was initially given the green light by FDA during 2002. The drug is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.
In a pivotal study, in patients with nonmyeloid malignancies undergoing myelosuppressive chemotherapy associated with a clinically significant incidence of febrile neutropenia, treatment with Neulasta has been demonstrated to significantly reduce the incidence of febrile neutropenia as well as hospitalizations related to febrile neutropenia and the use of IV antibiotics.
During July 2015, the labeling for the novel proteasome inhibitor Kyprolis (carfilzomib) was expanded by the Food and Drug Administration via the priority-review process. U.S. regulators approved the supplemental New Drug Application for Kyprolis for Injection in combination with Revlimid (lenalidomide) and dexamethasone (KRd) for treating patients with multiple myeloma who have received one to three prior lines of therapy.
Kyprolis is also indicated under FDA accelerated approval as a single agent for treating patients with multiple myeloma who have received at least two prior therapies including bortezomib and an immunomodulatory agent and have shown disease progression on or within 60 days of completion of the last therapy.
Additional FDA priority-review status for a Kyprolis sNDA was announced by Amgen on Sept. 18, 2015. The U.S. regulatory agency accepted for priority review the sNDA of Kyprolis for Injection for patients with relapsed multiple myeloma. The sNDA is designed to expand the approved indication to include Kyprolis in combination with dexamethasone for patients who have received at least one prior therapy.
Amgen announced during March 2015 results from a planned interim analysis demonstrating that the Phase III head-to-head clinical trial ENDEAVOR evaluating Kyprolis in combination with low-dose dexamethasone compared to Velcade (bortezomib) and low-dose dexamethasone met the primary endpoint of progression-free survival (PFS). Patients with relapsed multiple myeloma treated with Kyprolis lived twice as long without their disease worsening, showing statistically and clinically significant superiority versus Velcade.
In other Kyprolis R&D news, during April 2015 Amgen announced the initiation of a Phase III study for the drug with weekly dosing in relapsed and refractory multiple myeloma.
Regulatory applications for Kyprolis have been filed with regulatory health bodies globally. Kyprolis has been designated as an Orphan Drug and is undergoing accelerated assessment in the European Union for relapsed multiple myeloma. The drug came over to Amgen via the Onyx acquisition.
In the area of nephrology, during February 2015 Amgen announced positive results from a head-to-head Phase III study pitting etelcalcetide (formerly AMG 416) versus cinacalcet for treating secondary hyperparathyroidism in patients with chronic kidney disease receiving hemodialysis. The clinical trial met the primary endpoint of non-inferiority of AMG 416 compared to cinacalcet.
Amgen is hoping that etelcalcetide will be the first calcimimetic agent that can be administered intravenously. In early September 2015, a Marketing Authorization Application (MAA) was filed with the European Medicines Agency through the centralized procedure for etelcalcetide for treating secondary hyperparathyroidism (SHPT) in adult patients with chronic kidney disease (CKD) on hemodialysis therapy.
As a novel calcimimetic agent, etelcalcetide suppresses the secretion of parathyroid hormone. The drug is administered intravenously three times weekly at the end of each dialysis session. Etelcalcetide works by binding to and activating the calcium-sensing receptor on the parathyroid gland, thereby causing decreases in parathyroid hormone (PTH). Sustained PTH elevations are associated with significant clinical consequences for patients with CKD.
The MAA filing for etelcalcetide includes data from three Phase III trials, each of which met their primary endpoints, including two pooled placebo-controlled studies in 1,000-plus patients and a head-to-head trial evaluating etelcalcetide versus cinacalcet. Amgen markets Mimpara (cinacalcet), which is the first oral calcimimetic agent approved by the European Medicines Agency for treating SHPT in patients with CKD on dialysis. The product is additionally available in the EU for treating hypercalcemia in 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 (as defined by relevant treatment guidelines), but in whom parathyroidectomy is not clinically appropriate or is contraindicated. Mimpara binds to the calcium-sensing receptor, resulting in a reduction in PTH levels by inhibiting PTH synthesis and secretion. Also, the reductions in PTH lower serum calcium and phosphorus levels.
Amgen and UCB revealed on Sept. 1, 2015, top-line results from the STRUCTURE trial (STudy evaluating effect of ozUmab Compared with Teriparatide in postmenopaUsal women with osteoporosis at high risk for fracture pReviously treated with bisphosphonatE therapy). The clinical study – known as NCT01796301 – met the primary endpoint, showing a statistically significant difference in favor of romosozumab in the percent change of total hip bone mineral density (measured by DXA) through 12 months. The Phase III, multi-center, international, randomized, open-label, teriparatide-controlled trial assessed safety, tolerability and efficacy of romosozumab in women with postmenopausal osteoporosis.
Romosozumab is an investigational bone-forming monoclonal antibody yet to approved by any regulatory authority for treating osteoporosis. The drug is designed to work by inhibiting the protein sclerostin, thereby increasing bone formation and decreasing bone breakdown. Romosozumab is being studied for its potential to reduce fracture risk in an extensive worldwide Phase III program. This program includes two large fracture studies comparing romosozumab to either placebo or active comparator in over 10,000 postmenopausal patients with osteoporosis. Initial results from the Phase III trial FRAME are expected during first-half 2016.
Amgen during June 2015 reported results from a Phase III study demonstrating Vectibix improves overall survival in chemorefractory wild-type KRAS metastatic colorectal cancer compared to best supportive care. The study met the secondary endpoint of overall survival in wild-type RAS metastatic colorectal cancer.
Composed of the active chemical panitumumab, Vectibix is the first fully human anti-EGFR antibody approved by U.S. regulators for treating metastatic colorectal cancer (mCRC). Vectibix was cleared for U.S. marketing 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.
During May 2014, Vectibix was approved by FDA, for use in combination with FOLFOX, as first-line treatment in patients with wild-type KRAS (exon 2) mCRC. With this regulatory nod, 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.
Phase III data revealed at ASCO in early June 2015 demonstrated that Prolia significantly reduced bone fractures in breast cancer patients receiving aromatase inhibitors. The clinical trial shows that adjuvant Prolia therapy reduced fractures by 50 percent in postmenopausal women with non-metastatic breast cancer.
Prolia is the first approved therapy that specifically targets RANK Ligand, an essential regulator of bone-removing cells (osteoclasts). Prolia is FDA-approved for treating postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy. The drug is additionally available for treatment to increase bone mass in men with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy.
Deals & Collaborations
Amgen is building a cardiovascular drug portfolio. As part of this effort, the company reached a deal during mid-September 2015 to acquire Dezima Pharma B.V. The privately held, Netherlands-based biotech company has concentrated on developing innovative treatments for dyslipidemia. Amgen was responsible for $300 million in cash at closing and up to $1.25 billion in other payments if certain development and sales milestones are achieved.
The transaction bolsters Amgen’s cardiovascular portfolio with a late-stage, oral cholesteryl ester transfer protein (CETP) inhibitor known by the product code TA-8995. In a Phase IIb clinical trial for dyslipidemia, TA-8995 reduced low-density lipoprotein cholesterol by 45 to 48 percent versus baseline. LDL-C reduction was consistent when the potential new drug compound was administered as monotherapy or in combination with statins.
“TA-8995 has demonstrated dramatic LDL-C lowering,” noted Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “With a portfolio of TA-8995 and Repatha, our recently launched LDL-C lowering PCSK9 inhibitor, we will be able to offer more treatment options with different mechanisms of action and modes of administration across varying LDL-C levels and risk profiles.”
Amgen’s cardiovascular portfolio additionally includes omecamtiv mecarbil, a small molecule activator of cardiac myosin in Phase II clinical development. The new drug candidate is being studied for the treatment of heart failure in collaboration with Cytokinetics Inc. Phase II data from the COSMIC-HF heart failure clinical trial is expected during fourth-quarter 2015.
In addition to the Dezima transaction, Amgen announced another deal on the same day (Sept. 16, 2015). Amgen and Xencor Inc. entered into a research and license pact to develop and commercialize novel therapeutics in the fields of cancer immunotherapy and inflammation. The research collaboration unites Amgen’s capabilities in target discovery and protein therapeutics with Xencor’s XmAb bispecific technology platform.
Xencor is a clinical-stage biopharma company developing engineered monoclonal antibodies for treating asthma and allergic diseases, autoimmune diseases and cancer. At least eight candidates have been engineered with Xencor’s XmAb technology and are undergoing clinical development internally and with partners.
Through the collaboration, molecular engineering by Xencor and the preclinical development of bispecific molecules for five programs proposed by Amgen will leverage XmAb bispecific Fc domains to make half-life extended T cell engagers and dual targeting bispecific antibodies. The transaction additionally includes a preclinical bispecific T cell engager program directed at CD38 and CD3 for multiple myeloma.
Amgen is fully responsible for preclinical and clinical development as well as commercialization globally. Xencor gains a $45 million upfront payment and up to $1.7 billion in clinical, regulatory and sales milestone payments in total for the six programs. Xencor is eligible to receive mid to high single-digit royalties for candidates directed against Amgen’s targets, as well as high single to low double-digit royalties for Xencor’s CD38 bispecific T cell engager.
“We are pleased to be joining forces with Xencor to expand our immuno-oncology and inflammation position by leveraging Amgen’s antibodies and Xencor’s bispecific antibody platform,” Dr. Harper comments. “We are especially excited about the T cell-engaging bispecific antibody directed against CD38, which complements Amgen’s BiTE platform, while growing our hematology and oncology portfolio that includes two bispecific T cell engager antibodies, Blincyto (blinatumomab) and AMG 330, as well as Kyprolis (carfilzomib) for relapsed multiple myeloma.”
The novel CD33/CD3 BiTE antibody AMG 330 is being developed to recruit T cells to recognize and kill CD33 expressing acute myeloid leukemia target cells.
Bispecific technologies seek to engineer monoclonal antibodies to bind two unique drug targets, whereas traditional antibodies are designed to bind to a single antigen target. According to Amgen, this approach represents a powerful opportunity in immuno-oncology to simultaneously engage immune cells and tumor cells to localize anti-tumor immune activity where it is needed most.
Amgen entered into a neuroscience collaboration with Novartis for Alzheimer’s disease and migraine programs as announced at the beginning of September 2015. According to Amgen, the agreement accelerates its potential entry into Alzheimer’s disease by teaming up with Novartis on a differentiated and genetically validated Alzheimer’s disease program directed at genetically predisposed individuals at risk of developing AD. The collaboration additionally allows Amgen to concentrate on the commercialization of its migraine programs in the United States, Canada and Japan, while leveraging Novartis’ strong commercial capabilities in neuroscience throughout Europe and other global markets.
The collaboration joins together both company’s BACE (beta-site APP-cleaving enzyme-1) programs targeting Alzheimer’s disease into a worldwide joint-commercialization and co-development arrangement. Novartis’ Phase I/IIa BACE inhibitor (CNP520) will be the lead molecule and each company’s pre-clinical BACE inhibitor programs will be potential follow-ons. The oral drug CNP520 is designed to prevent the production of different forms of amyloid and has the potential to prevent, slow or delay symptoms associated with Alzheimer’s disease.
Amgen will make upfront and milestone payments, and is responsible for disproportional R&D costs for an agreed-upon period followed by a 50/50 cost and profit share arrangement. CNP520 is planned to be part of a pioneering prevention study, in collaboration with the Banner Alzheimer’s Institute. Amgen became the first company to clone the BACE gene in 1999, and subsequent genetic validation of the BACE target was confirmed by its subsidiary deCODE Genetics during 2012.
Novartis receives worldwide joint-development rights and commercial rights outside of the United States, Canada and Japan to the investigative molecules in Amgen’s migraine portfolio program. This includes AMG 334 in Phase III and AMG 301 in Phase I, as well as an option to commercialize an additional early-stage Amgen molecule in those countries. In exchange for territory rights, Novartis will fund disproportional amounts of worldwide R&D expenses for an agreed-upon period on the migraine programs and pay Amgen double-digit royalties on sales.
“We are very pleased to be joining forces with Novartis on two important neuroscience programs where there remains high unmet medical need,” Dr. Harper stated. “Our collaboration on BACE inhibition reflects Amgen’s strategic focus on genetically validated drug candidates while our collaboration in migraine creates an opportunity to more rapidly advance AMG 334 on a global scale.”
AMG 334 is a fully human monoclonal antibody undergoing development for the prevention of migraine. The new product candidate targets the calcitonin gene-related peptide (CGRP) receptor, which is believed to transmit signals that can result in capacitating pain. AMG 334 is undergoing assessment in several large worldwide, randomized, double-blind, placebo-controlled trials to evaluate its safety and efficacy in migraine prevention.
During June 2015, Amgen announced positive interim results from the company’s open-label extension of the worldwide Phase II, double-blind, placebo-controlled trial evaluating the safety and efficacy of AMG 334 for the prevention of episodic migraine. Patients experienced sustained reductions in monthly migraine days and consistent safety profile from blinded phase at 52 weeks. Nearly one in five patients experienced 100 percent reduction in monthly migraine days at one year.
Amgen and fellow biotechnology industry leader Roche announced a collaboration in early June 2015 for a Phase Ib study. The study is assessing the safety and efficacy of Amgen’s talimogene laherparepvec in combination with Roche’s atezolizumab (also known as MPDL3280A) in patients with triple-negative breast cancer and colorectal cancer with liver metastases. The investigational oncolytic immunotherapy alimogene laherparepvec is designed to selectively replicate in tumors (but not normal tissue) and to initiate an immune response to target cancer cells. The investigational monoclonal antibody atezolizumab is designed to interfere with the PD-L1 protein. The rationale for combining these investigational agents is to activate an anti-tumor immune response with talimogene laherparepvec and to block inhibitory T cell checkpoints with atezolizumab, potentially increasing the anti-tumor activity relative to each drug alone.
Global regulatory reviews – including in the United States and European Union – are under way for a monotherapy indication for talimogene laherparepvec for treating patients with regionally or distantly metastatic melanoma.
Amgen and Merck & Co. agreed in May 2015 to expand their collaboration to evaluate the efficacy and safety of talimogene laherparepvec in combination with Merck’s anti-PD-1 therapy Keytruda (pembrolizumab) in a Phase I, open-label trial of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). The companies also announced that a global, randomized Phase III study to evaluate the combination in patients with regionally or distantly metastatic melanoma was being initiated. As previously announced, the compounds are being investigated in a Phase I, open-label study in this patient population.
Each immunotherapy is designed to modulate the immune system. Talimogene laherparepvec is designed to selectively replicate in tumors (but not normal tissue) and to initiate an immune response against cancer cells. The humanized monoclonal antibody Keytruda blocks the interaction between PD-1 (programmed death receptor-1) and its ligands, PD-L1 and PD-L2.
Kicking off 2015, Amgen and Kite Pharma Inc. announced a strategic cancer immunotherapy collaboration to advance the application of novel chimeric antigen receptor (CAR) T cell therapies. The alliance joins together Amgen’s oncology targets and Kite’s leading CAR T cell therapy platform to develop new therapeutic candidates.
Kite received a $60 million up-front payment from Amgen and is eligible for up to $525 million in regulatory and sales milestone payments per Amgen program, as well as tiered high single-digit to double-digit royalties for sales and license of Kite’s intellectual property for CAR T cell products. Amgen is eligible to receive up to $525 million in milestone payments per Kite program along with tiered single-digit sales royalties.
“Amgen is an ideal partner for us, based on their strong presence in oncology and the company’s broad array of cancer targets optimally suited for combining with our CAR technologies. We are proud to announce this unique collaboration and its validation of our R&D expertise, intellectual property position, and therapeutic manufacturing and processing capabilities,” commented Arie Belldegrun, M.D., FACS, Kite Pharma’s president and CEO. “We believe that the therapeutic candidates resulting from the collaboration will have the potential to dramatically transform CAR approaches and to become some of the most powerful therapies for the treatment of cancer.”
Also during January 2015, Amgen and The University of Texas MD Anderson Cancer Center announced a research collaboration. The agreement is concentrated on Amgen’s bispecific T cell engager (BiTE) antibody constructs, an immunotherapy that serves as a “bridge” between T cells and cancer cells.
The companies are identifying targets for this therapy in myelodysplastic syndrome (MDS), a bone marrow disorder in which the body does not produce sufficient healthy blood cells. MDS affects primarily older adults over age 60 and can cause severe anemia, possibly leading to development of the blood cell cancer AML.
The collaboration enables Amgen and MD Anderson to join forces in a research partnership aimed at taking new drug development from “A to Z.” The deal provides for joint development of new agents under pre-determined terms. Amgen retains all commercial rights, and MD Anderson is eligible to receive milestone payments and royalties upon successful achievement of key objectives.
Amgen’s first biosimilar on track for 2017 market debut
Amgen has nine biosimilar molecules in development representing a $3-plus billion market opportunity. One-third of that biosimilar portfolio was added by Amgen during 2014 The company anticipates launching five of the nine biosimilar molecules to the marketplace between 2017 and 2019.
Amgen is working on bringing to market ABP 501, which is being developed as a biosimilar candidate to adalimumab. The anti-TNF-alpha monoclonal antibody adalimumab is approved in many countries under the trade name Humira for treating inflammatory diseases such as rheumatoid arthritis, plaque psoriasis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease and ulcerative colitis. Humira, which is marketed by AbbVie Inc., was the world’s top-selling prescription medicine during 2014.
Amgen announced during early February 2015 positive top-line results from a Phase III trial evaluating the efficacy and safety of ABP 501 versus adalimumab in patients with moderate-to-severe rheumatoid arthritis. Primary efficacy analysis showed clinical equivalence, and this was the second positive Phase III trial for ABP 501.