Amgen's Growth Playbook: Unveiling Key Drivers and Future Trends in Biopharmaceuticals

1. Overview of Amgen’s Sales Performance

Amgen’s biopharmaceutical portfolio has shown consistent revenue over the last several years (2016 to 2023), despite significant shifts in sales performance across key products. With certain products experiencing declines due to biosimilar competition and pricing pressures, others have grown substantially, reflecting Amgen's ability to adapt and focus on emerging growth drivers.

2. Major Products: Sales Trends and Insights

Insights from Product Sales from 2016 to 2023 (in Billion of U.S. $). Data is sourced from SEC (10-K). This report is for informational purposes only and does not constitute financial advice.

ENBREL (etanercept)

• Treatment Type: Fusion protein  (protein-based therapy); Tumor Necrosis Factor (TNF) inhibitor

• Indications: Rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis

• 2016 Sales: $5.97 billion

• 2023 Sales: $3.70 billion

• Overall Decline: -38%

Science:

ENBREL is one of Amgen’s cornerstone biologics, primarily used in the treatment of autoimmune diseases by blocking TNF. TNF, a protein factor in the body, is produced naturally by the immune system and plays a role in fighting infections. However, in certain autoimmune diseases like rheumatoid arthritis, psoriasis, and Crohn’s disease, the body produces too much TNF, leading to excessive inflammation and damage to tissues and joints. Etanercept binds specifically to tumor necrosis factor (TNF) and thereby modulates biological processes that are induced or regulated by TNF (drugbank.com).

Mechanism of action of few anti-TNF biologics, including etanercept (sold by Amgen in US and Canada, and Pfizer internationally under the brand name of ENBREL), adalimumab (sold by AbbVie under the brand name of Humira), golimumab (sold by Janssen Biotech, as subsidiary of Johnson & Johnson, under the brand name of Simponi), and infliximab (sold by Janssen Biotech, as subsidiary of Johnson & Johnson, under the brand name of Remicade). These drugs (biosimilars) work by binding to both soluble (sTNF) and membrane-bound TNF (tmTNF), preventing it from interacting with its receptors (TNFR1 and TNFR2 - not shown) on the surface of immune cells like macrophages and CD4+ T cells. By blocking TNF from binding to its receptors, these drugs stop the inflammatory signals that normally activate these immune cells. Image is adopted from Steeland et al, 2018.

Analysis:

ENBREL sales peaked in 2016 (in the timeframe 2023-2016) and have experienced a steady decline since, due to several factors:

• Biosimilar Competition: While biosimilars like Erelzi (etanercept-szzs by Sandoz) and Eticovo (by Samsung Bioepis) have been approved, patent protections in the U.S. have delayed full competition. Nonetheless, pricing pressures and competition in non-U.S. markets have contributed to the sales decline.

• Patent Protection: ENBREL maintains U.S. patent protection until 2029, delaying biosimilar erosion in this critical market.

• Pricing Pressures: Significant government regulations and insurers pushing for cost savings are driving down pricing.

• Market Saturation: ENBREL has been on the market for over two decades, and newer biologics, such as Humira (adalimumab), Remicade (infliximab), and JAK inhibitors, have entered the market.

Ongoing Role: Despite the decline, ENBREL still contributed $3.70 billion in sales in 2023, remaining a key revenue driver until its patent expiration.

Future Outlook: ENBREL will likely continue to face pricing pressures, and once the U.S. patent expires in 2029, biosimilars will further erode its market share.

Prolia (denosumab)

• Treatment Type: Monoclonal antibody  (protein-based therapy); RANK ligand (RANKL) inhibitor

• Indications: Osteoporosis, bone loss

• 2016 Sales: $1.64 billion

• 2023 Sales: $4.05 billion

• Cumulative Growth: +147.58%

Science:

Prolia (denosumab) is a highly effective treatment for osteoporosis, particularly in postmenopausal women at risk of fractures. It works by inhibiting the RANK ligand (RANKL), a key protein that promotes bone resorption—the process of breaking down bone tissue. RANKL binds to its receptor, RANK, on osteoclasts and their precursors, triggering bone loss. In conditions of excessive bone resorption, the body’s natural defenses are overwhelmed by RANKL activity. Prolia blocks the interaction between RANKL and RANK, preventing osteoclast formation, function, and survival. This inhibition reduces bone resorption while simultaneously increasing bone mass and strength (drugbank.com).

Mechanism of action of Prolia (denosumab). Denosumab's binding to RANKL effectively blocks its interaction with the RANK receptor on both immature and mature osteoclasts. By inhibiting this key signaling pathway, denosumab prevents osteoclast maturation, activity, and survival, leading to a significant reduction in bone resorption and a suppression of bone turnover. Image is adopted from Sidlauskas K et al, 2014.

Analysis:

• Growing Demand: The aging population and increased diagnosis of osteoporosis have led to rising demand for Prolia.

• Competition: The treatment landscape for osteoporosis is competitive, with alternatives ranging from biosimilars like Jubbonti and Wyost (both by Sandoz) to other monoclonal antibodies such as Evenity (Amgen and UCB). Additionally, bisphosphonates (e.g., Fosamax by Merck, Actonel by Warner Chilcott, and Reclast by Novartis), SERMs (e.g., Evista by Eli Lilly), and parathyroid hormone analogues (e.g., Forteo by Eli Lilly and Tymlos by Radius Health) provide healthcare providers with varied options for osteoporosis management.

• Global Expansion: Prolia’s strong presence in international markets, combined with its long-term treatment potential (administered twice a year), has contributed to its robust growth.

• Clinical Efficacy: Its ability to prevent fractures more effectively than some traditional osteoporosis treatments has made it a preferred option for healthcare providers.

Record Sales in 2023: In 2023, Prolia achieved record sales of $4.05 billion, reinforcing its status as a cornerstone product for Amgen.

Long-Term Growth Potential: As the population continues to age, Prolia’s market potential will remain strong, particularly in expanding its presence in regions where osteoporosis remains undertreated.

XGEVA (denosumab)

• Treatment Type: Monoclonal antibody  (protein-based therapy); RANK ligand (RANKL) inhibitor

• Indications: Bone metastases, prevention of skeletal-related events (SREs)

• 2016 Sales: $1.53 billion

• 2023 Sales: $2.11 billion

• Cumulative Growth: +38.13%

Year-over-Year (YoY) Trends:

• 2023: -4.64% YoY decline

• 2022: +0.19% YoY growth

• 2021: -5.90% YoY decline

Analysis:

XGEVA, like Prolia, is based on denosumab, but it is used primarily in oncology to treat bone metastases and prevent skeletal-related events (SREs) such as fractures.

• High Demand in Cancer Care: XGEVA is widely used in the treatment of cancers like breast, prostate, and lung cancer that spread to the bones. It helps prevent complications such as fractures and spinal cord compression.

• Geographic Expansion: Expansion into regions with high cancer incidence has supported XGEVA’s steady growth.

Challenges: Recent YoY declines in 2021 and 2023 are attributed to increasing competition from newer oncology therapies, such as immune checkpoint inhibitors and CAR-T therapies, as well as pricing pressures in international markets.

Future Outlook: While XGEVA faces competitive pressures, its continued use in oncology for preventing bone metastasis complications positions it as a long-term revenue source for Amgen.

Otezla (apremilast)

• Treatment Type: Small molecule; Phosphodiesterase-4 (PDE4) inhibitor

• Indications: Psoriasis, psoriatic arthritis

• 2019 Acquisition by Amgen

• 2023 Sales: $2.19 billion

Year-over-Year (YoY) Trends:

• 2023: +4.57% YoY growth

• 2022: -1.70% YoY decline

• 2021: -2.40% YoY decline

Science: Otezla (apremilast) is a treatment for inflammatory conditions like psoriasis and psoriatic arthritis. While its full mechanism of action isn’t completely understood, it is known that Otezla inhibits phosphodiesterase 4 (PDE4), an enzyme that helps regulate inflammation. By blocking PDE4, Otezla increases levels of cyclic adenosine monophosphate (cAMP), which helps reduce the production of inflammatory proteins. These proteins are responsible for causing symptoms such as skin lesions, mouth ulcers, and joint pain. By lowering the levels of these inflammatory signals, Otezla helps relieve the symptoms of psoriatic conditions and Behcet's disease (drugbank.com).

Mechanism of action of Otezla (apremilast). In monocytes and dendritic cells, an enzyme called PDE4 normally breaks down cAMP, a molecule involved in cell signaling. When apremilast inhibits PDE4, it allows cAMP levels to rise. This increase in cAMP activates another molecule called PKA, which then turns on certain proteins, including CREB. CREB promotes the production of IL-10, an anti-inflammatory protein. At the same time, apremilast reduces the activity of NF-κB, a protein that drives inflammation, leading to lower levels of inflammatory signals like IL-23, TNF-α, and IFN-γ. As a result, inflammation decreases, and fewer immune cells gather in the skin and joints, helping to relieve symptoms of psoriasis and related conditions. Image is adopted from Cauli et al, 2014.

Analysis:

Since Amgen acquired Otezla from Celgene in 2019, the product has experienced steady growth, although small YoY declines occurred in 2021 and 2022.

• Market Demand for Psoriasis Treatment: As an oral treatment, Otezla offers a convenient alternative to biologics (typically injectables)—typically injectables like Humira (by AbbVie), Stelara (by Johnson & Johnson), Cosentyx (by Novartis), and Tremfya (by Johnson & Johnson). This oral option makes it attractive for both patients and physicians.

• Geographic Expansion: Amgen has continued to expand Otezla’s presence globally, particularly in markets with a high prevalence of psoriasis.

Challenges: Otezla faces competition from biologics such as Humira and Cosentyx, and newer IL-17 and IL-23 inhibitors, which have led to small YoY declines in prior years.

Rebound in 2023: In 2023, Otezla saw a +4.57% YoY growth, reflecting the product's resilience and Amgen’s strategic investments in expanding its market reach.

3. Emerging and High-Growth Products: Sales Performance Review (2023)

EVENITY (romosozumab)

• Treatment Type: Monoclonal antibody (protein-based therapy); Sclerostin inhibitor

  SIndications: Osteoporosis

• 2023 Sales: $1.16 billion

Year-over-Year (YoY) Trends:

• 2023: +32.15% YoY growth

• 2022: +32.65% YoY growth

Science:

Evenity (romosozumab) treats osteoporosis in postmenopausal women at high risk of fractures or who haven't responded to other treatments. It works by blocking the protein sclerostin, which normally inhibits bone formation. By stopping sclerostin, Evenity promotes bone growth through the Wnt signaling pathway and also reduces bone breakdown by lowering RANKL levels, which decreases osteoclast activity. This dual effect of increasing bone formation and reducing bone resorption makes Evenity unique among osteoporosis treatments (drugbank.com).

Mechanism of action of Evenity (romosozumab). This figure shows how romosozumab works compared to other osteoporosis treatments like teriparatide and abaloparatide. While teriparatide and abaloparatide help build bone by balancing bone breakdown and formation, romosozumab has a unique action. It not only helps increase bone formation through osteoblasts but also reduces bone breakdown through osteoclasts at the same time, making it more effective in treating osteoporosis. This dual action is what sets romosozumab apart from the other treatments. Image is adopted from Ferrari, 2018.

Analysis:

• Market Demand: With the aging global population and the increased awareness of osteoporosis treatment options, EVENITY has quickly gained market share in regions like Europe and Asia.

• Clinical Efficacy: Its ability to reduce fractures while promoting bone growth has made it a key treatment in the osteoporosis space. EVENITY's superior efficacy compared to traditional osteoporosis drugs has helped it quickly gain traction.

Strategic Importance: In 2023, EVENITY reached $1.16 billion in sales, reinforcing its role as a key growth driver in Amgen’s bone health portfolio. Its future growth potential is substantial as osteoporosis cases rise globally, positioning EVENITY for long-term success in the market.

BLINCYTO (blinatumomab)

• Treatment Type: Bi-specific T-cell engager (BiTE) antibody construct (protein-based therapy); CD19 engager

• Indications: Acute lymphoblastic leukemia (ALL)

• 2023 Sales: $0.86 billion

• YoY Trends: +47.52% YoY growth in 2023

Science:

Blincyto (blinatumomab) is an innovative treatment for certain types of B-cell malignancies, such as acute lymphoblastic leukemia (ALL). It belongs to the BiTE-class (bi-specific T-cell engager) of monoclonal antibodies. Blinatumomab works by connecting two key proteins: CD3, found on T-cells, and CD19, commonly present on cancerous B-cells. By bridging T-cells and tumor cells, Blincyto redirects the body’s immune response to target and destroy the cancer cells. This immune activation leads to the release of signaling molecules that help T-cells attack and kill the tumor cells, making Blincyto an effective therapy for CD19-positive B-cell malignancies. It was first approved by the FDA in 2014 for treating relapsed and refractory B-cell precursor acute lymphoblastic leukemia (drugbank.com).

Mechanism of action of Blincyto (blinatumomab). Blinatumomab is a bispecific T-cell engager (BiTE) that targets CD19 on B-cells and CD3 on T-cells. By linking T-cells to B-cells, including cancerous B-cells like those in acute lymphoblastic leukemia (ALL), it activates the T-cells to release cytokines (interleukins, interferon, and TNF) and cytotoxic proteins (perforin and granzymes) that destroy the tumor cells. This immune response leads to the elimination of CD19+ tumor cells, making Blincyto an effective therapy for certain B-cell malignancies. Image is adopted from Lee et al, 2016.

Analysis:

• Clinical Significance: BLINCYTO has been a breakthrough in treating minimal residual disease (MRD) in patients with ALL, helping reduce the risk of relapse. Its use in high-risk leukemia patients makes it a critical part of Amgen’s hematology portfolio.

• Market Growth: The +47.52% YoY growth in 2023 reflects its increasing adoption in the treatment of ALL, particularly in patients who do not respond to traditional therapies.

Challenges: While CAR-T therapies like Kymriah (by Novartis) and Yescarta (by Gilead Sciences) have gained prominence in the leukemia space, Blincyto continues to be favored in certain patient populations, especially those not suited for CAR-T therapy. Its unique BiTE technology makes it a vital treatment option for addressing unmet needs in leukemia care.

Strategic Importance: BLINCYTO’s continued growth in the ALL treatment space underscores its strategic importance for Amgen, and its bi-specific T-cell engagement mechanism differentiates it from other therapies. Its ability to target specific cancer cells offers a promising future in hematology treatments.

TEPEZZA (teprotumumab)

• Treatment Type: Monoclonal antibody (protein-based therapy) ; IGF-1R inhibitor

• Indications: Thyroid eye disease (TED)

• 2023 Sales: $0.45 billion

Science:

Tepezza (teprotumumab) is the first FDA-approved treatment for thyroid eye disease (TED), a rare condition commonly linked to Graves' disease. It works by targeting and inhibiting the insulin-like growth factor 1 receptor (IGF-1R), which plays a key role in the inflammation and tissue remodeling seen in TED. By blocking IGF-1R, Tepezza reduces these effects, helping to relieve symptoms such as proptosis (bulging eyes) and optic neuropathy. As the first non-surgical treatment for TED, Tepezza marks a major advancement in managing this condition (drugbank.com).

Mechanism of action of Tepezza (teprotumumab). In both the acute and chronic phases of thyroid eye disease (TED), IGF-1R is overexpressed on orbital fibroblasts (OFs). In the acute phase, activation of the IGF-1R and TSHR pathways triggers the release of inflammatory cytokines, increases the production of hyaluronic acid (HA) and other extracellular matrix proteins, and promotes the differentiation of fibroblasts into adipocytes or myofibroblasts, leading to tissue expansion. In the chronic phase, IGF-1R overexpression continues, sustaining tissue expansion. Abbreviations: RANTES (also known as CCL5), HA (hyaluronic acid), and GAGs (glycosaminoglycans). Image is adopted from Ugradar et al, 2021.

Analysis:

• Unmet Medical Need: Prior to TEPEZZA, TED patients had limited treatment options, often requiring surgery or less effective therapies. The introduction of TEPEZZA filled a significant unmet need for TED patients, contributing to its rapid adoption.

• Rapid Market Penetration: TEPEZZA achieved $0.45 billion in sales in 2023, demonstrating its growth potential as it gained market share quickly due to its strong clinical efficacy in improving symptoms like proptosis (bulging eyes) and reducing eye pain and inflammation.

Emerging Competitors: Tepezza faces potential competition from late-stage therapies like Veligrotug (Viridian Therapeutics), IBI311 (Innovent Biologics, for the Chinese market), and RVT-1401 (Immunovant), which may provide alternatives in the future pending successful trials and approvals.

Strategic Importance: TEPEZZA’s success in addressing a previously underserved patient population makes it a high-growth product for Amgen. As awareness of TED increases and Amgen expands the availability of TEPEZZA globally, sales are expected to continue climbing, positioning the product as a valuable addition to Amgen’s portfolio.

Summary of Emerging and High-Growth Products

• EVENITY: EVENITY generated $1.16 billion in sales in 2023, with over +32% YoY growth, quickly establishing itself as a vital treatment for osteoporosis with both bone-building and bone-maintenance properties.

• BLINCYTO: BLINCYTO achieved $0.86 billion in sales, experiencing +47.52% YoY growth in 2023. Its BiTE technology continues to make it a unique and important treatment option for patients with acute lymphoblastic leukemia (ALL).

• TEPEZZA: TEPEZZA recorded $0.45 billion in sales in 2023, showing promising growth potential in treating thyroid eye disease (TED), filling a significant unmet need in this rare condition.

Closing Statement

Amgen’s diversified biopharmaceutical portfolio reflects its strategic focus on both established biologics and high-growth therapies. While legacy products such as ENBREL continue to face challenges from pricing pressures and potential biosimilar competition, their ongoing contributions remain significant. Meanwhile, newer and high-growth products, such as Prolia, EVENITY, and BLINCYTO, showcase Amgen’s ability to innovate and capture market share in emerging therapeutic areas like osteoporosis and oncology.

Prolia's impressive growth trajectory, combined with EVENITY's rapid market adoption, positions Amgen well in the aging population segment. Meanwhile, therapies like BLINCYTO and TEPEZZA demonstrate the company's strategic push into specialized markets, addressing previously unmet needs with groundbreaking treatments.

As Amgen navigates patent cliffs, increasing competition, and pricing pressures, its ability to develop and commercialize new therapies while maximizing the value of its existing portfolio will be critical to maintaining long-term growth and market leadership.

Disclaimer:

This research report contains information generated with the assistance of artificial intelligence. While every effort has been made to ensure accuracy and relevance, the analysis presented here may contain errors, omissions, or outdated data. Readers are encouraged to verify the information independently before making any decisions based on the content. This report is intended for informational purposes only and should not be considered professional or financial advice. Neither the author nor the AI service provider assumes responsibility for any inaccuracies or the use of the information provided.