Sandoz

Sandoz Biologics License Application for proposed biosimilar denosumab accepted by US FDA

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  • Submission supported by comprehensive analytical and clinical data package
  • Denosumab indicated for treating variety of conditions including osteoporosis in postmenopausal women1,2
  • Sandoz continues to build biosimilars portfolio to increase patient access to high-quality therapies and support healthcare system sustainability

Basel, February 06, 2023 — Sandoz, a global leader in off-patent (generic and biosimilar) medicines, today announced that the US Food and Drug Administration (FDA) has accepted its Biologics License Application (BLA) for proposed biosimilar denosumab.

The application includes all indications covered by the reference medicines Prolia® (denosumab)* and Xgeva® (denosumab)* for treating a variety of conditions, including osteoporosis in postmenopausal women and in men at increased risk of fractures, treatment-induced bone loss, prevention of skeletal related complications in cancer that has spread to the bone, giant cell tumor of the bone, and treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.1,2

“In addition to being an important medicine for cancer of the bone, denosumab is critical in the treatment of osteoporosis and potential prevention of osteoporosis-related fractures that so many women over 50 are at risk of,” said Keren Haruvi, President, Sandoz Inc. and Head of North America.

“We are proud to be among the first to submit a BLA for a denosumab biosimilar as, if approved, it could increase patient access to an affordable, high-quality, potentially disease-modifying treatment across the US, while also delivering savings for healthcare systems.”

In the US alone, more than 10 million adults over age 50 are estimated to have osteoporosis, of whom more than 80% are women.3 It is predicted that one in two of these women and one in four men will have an osteoporosis-related fracture in their lifetimes.4 Osteoporosis-related fractures may lead to diminished quality of life, disability, and even death.5 

The BLA includes a comprehensive analytical and clinical data package, including data from the Phase I/III ROSALIA study. Results confirmed that the proposed biosimilar denosumab matches the reference medicine in terms of pharmacokinetics, pharmacodynamics, efficacy, safety and immunogenicity in women with postmenopausal osteoporosis; and contributes to demonstration of similarity, which is the basis for use in all indications.

Sandoz biosimilars help patients, in areas including immunology, oncology, supportive care and endocrinology, access critical and potentially life-changing medicines sustainably and affordably. Sandoz has a leading global portfolio with eight marketed biosimilars and a further 15-plus in various stages of development.

About denosumab

Denosumab is a human monoclonal antibody designed to bind to the RANKL protein, an activator of osteoclasts (cells involved in breaking down bone tissue).1 By binding to and inhibiting RANKL, denosumab decreases the production and activity of osteoclasts, resulting in a reduction of bone loss, and subsequently the likelihood of fractures and other serious bone conditions.6

References

  1. Amgen Inc. Prolia® (Denosumab): Prescribing Information. Available from: https://www.pi.amgen.com/-/media/Project/Amgen/Repository/pi-amgen-com/Prolia/prolia_pi.pdf [Last accessed: January 2023].
  2. Amgen Inc. Xgeva® (Denosumab): Prescribing Information. Available from: https://www.pi.amgen.com/-/media/Project/Amgen/Repository/pi-amgen-com/xgeva/xgeva_pi.pdf [Last accessed: January 2023].
  3. Wright, N.C., et al., The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res, 2014.29(11): p. 2520-6.
  4. Cleveland Clinic Osteoporosis: Symptoms, Causes, Tests & Treatment. Available from: https://my.clevelandclinic.org/health/diseases/4443-osteoporosis [Last accessed: January 2023].
  5. Osteoporosis and the Burden of Osteoporosis-Related Fractures. Available from: https://www.ajmc.com/view/a357_11ma7__dempster_s164to169 [Last accessed: January 2023].
  6. International Osteoporosis Foundation. Facts and Statistics. Available from: https://www.osteoporosis.foundation/facts-statistics/epidemiology-of-osteoporosis-and-fragility-fractures [Last accessed: January 2023].

Savings With Biosimilar Filgrastim Unclear

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A simulation analysis funded by Sandoz Inc is projecting cost savings or more than $40 million if their biosimilar filgrastim, known as filgrastim-sdnz (Zarxio), is used instead of the reference drug (Neupogen, Amgen) for the prevention and treatment of febrile neutropenia in breast cancer patients who are Medicare beneficiaries.

A poster of the new analysis was presented earlier this month during the San Antonio Breast Cancer Symposium (SABCS) 2018.

However, the authors of an unrelated “real-world” simulation study of the use of biosimilars for the same indication say that to date, cost savings have been “modest,” in part because of similar pricing.

This second study, from a private healthcare analytics group, was published online November 3 in JAMA Oncology.

In the first study, lead author Gary Puckrein, PhD, National Minority Quality Forum, Washington, DC, and colleagues carried out a simulation to estimate the potential out-of-pocket cost savings for Medicare patients with breast cancer who undergo treatment with filgrastim-sdnz instead of reference filgrastim.

The researchers also estimated potential savings to Medicare on payments for the administration of the same biosimilar rather than the reference drug for the treatment or prophylaxis of febrile neutropenia in beneficiaries with breast cancer.

The average out-of-pocket cost for patients and any reduction in Medicare payments per claim were then calculated for patients who received filgrastim-sdnz instead of brand-name filgrastim.

This was then extrapolated to simulate 1 million claims from 100,000 Medicare patients at an estimated 10 claims per patient.

The average cost savings per claim for each patient treated with filgrastim-sndz instead of reference filgrastim was $9.51, the researchers report.

Extrapolated to 100,000 beneficiaries — or 1 million claims — the simulation model estimated that Medicare beneficiaries would save approximately $9.6 million if they were treated with filgrastim-sndz. Medicare would see a reduction in payments of $32.9 million if the same strategy were adopted.

“It is important to understand that this is a simulation model, so further analyses of real-world patient cases are needed to more thoroughly understand the appropriate patients who should receive a filgrastim biosimilar, as well as dosing needs,” Carlos Sattler, MD, vice-president of clinical development and medical affairs at Sandoz, North America, told Medscape Medical News in an email.

“But the main message emanating from this study is that Medicare patients who were prescribed biosimilar filgrastim saved about $9.60 per claim relative to those who were prescribed reference filgrastim, and this underscores the potential value of biosimilars in saving money for patients,” he added.

More filgrastim-sndz is prescribed now in the United States than reference filgrastim, according to Sandoz.

In 2012, the total cost for treating hospitalizations for cancer-related neutropenia was $2.3 billion for adults in the United States.

More Modest

On the other hand, an investigation of the real-world safety and effectiveness of biosimilar filgrastim compared with the brand-name drug suggests that cost savings to commercially insured patients in the United States are modest.

In a retrospective observational study, Abiy Agiro, PhD, HealthCore Inc, Wilmington, Delaware, and colleagues analyzed 11,202 commercially insured adults who underwent chemotherapy and were treated with either reference filgrastim or one of two biosimilar agents — the Sandoz product, and tbo-tiligrastim (Granix, Teva) — over a period of almost 5 years.

“Patients were observed for 21 days postindex to assess filgrastim treatment cost (total and per day of use) and the incidence of FN [febrile neutropenia] and AEs [adverse events],” the researchers write.

Of this large group of patients, 13.7% were prescribed biosimilar filgrastim, they note. (The use of biosimilar filgrastim has risen steadily from 7% of filgrastim users in 2014 to 36% of users in the United States 2016.)

“Incidence rates of strict (neutropenia and fever) and broad (neutropenia or fever) definitions of FN were similar between the 2 groups,” the researchers indicate.

The cost differential between treating patients with either biosimilar compared to reference filgrastim was also not that dramatic; the mean cost of treating a single patient with any one of the three products was very similar.

Table. Treatment Costs for Biosimilar Filgrastim vs Reference Filgrastim

Biosimilar Filgrastim Tbo-Filgrastim (Granix, Teva) Filgrastim-sndz Reference Filgrastim
Mean cost per day of use $731.00 $765.00 $667.00 $748.00
Mean treatment cost per patient $2522 $2585.00 $2363.00 $2516.00

“The cost per day of use was 2.3% less for biosimilar filgrastim,” the researchers indicate. “[T]he mean total cost per patient and per day of use were 6.1% and 10.8% less for filgrastim-sndz (P = .07 and P < .001, respectively) and were marginally higher for tbo-filgrastim (2.7% and 2.3%, respectively),” they add.

Agiro and colleagues point out that savings associated with biosimilar versions of filgrastim have been modest because uptake of these agents has been slow and because current pricing for biosimilar drugs closely tracks that of the reference product.

Sandoz biosimilar etanercept recommended by FDA advisory committee for approval to treat multiple inflammatory diseases

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Sandoz, a Novartis division and leader in biosimilars, announced today that the US Food and Drug Administration (FDA) Arthritis Advisory Committee recommended approval of its proposed biosimilar etanercept. The committee voted unanimously (20-0), in support of biosimilar etanercept for all five indications of the reference product, including rheumatoid arthritis (RA), plaque psoriasis (PsO), psoriatic psoriasis (PsA), ankylosing spondylitis (AS) and polyarticular juvenile idiopathic arthritis (JIA).

 “We are encouraged by today’s favorable advisory committee recommendation for our proposed biosimilar etanercept,” said Mark McCamish, M.D., Ph.D., Head of Global Biopharmaceutical Development, Sandoz. “As a global market leader in biosimilars, we are pleased to move one step closer toward our goal of expanding patient access with our proposed biosimilar etanercept, and look forward to continuing to work with the FDA as they complete their review of our application.”

 The recommendation was provided after the presentation of data from a global development program including analytical, pre-clinical and clinical studies of the Sandoz biosimilar etanercept, which demonstrated biosimilarity to the reference product. Clinical studies included four comparative pharmacokinetic (PK) studies in 216 healthy volunteers** and a confirmatory efficacy and safety similarity study in 531 patients with chronic plaque psoriasis.

 The FDA frequently seeks the advice of its advisory committees as it reviews and decides whether to approve applications, although the agency does not always follow their recommendations.

 In December 2015, the European Medicines Agency (EMA) accepted Sandoz Marketing Authorization Application (MAA) for its biosimilar to Amgen’s EU-licensed Enbrel®, which seeks approval for the same indications as the reference product.

 Sandoz is committed to providing patient access to high-quality, life-enhancing biosimilars. It is the pioneer and global market leader and currently markets three biosimilars worldwide. Sandoz has a leading pipeline with several biosimilars in late stage development, including assets in immunology and oncology. As part of the Novartis Group, Sandoz is well-positioned to lead the biosimilars industry based on its experience and capabilities in development, manufacturing and commercialization.

 

About GP2015

GP2015, the Sandoz proposed biosimilar of Enbrel®, has been studied in a global development program, which included a comprehensive comparison of GP2015 and Enbrel® at the analytical, non-clinical, and clinical levels, including data from four pharmacokinetic (PK) studies (GP15-101, GP15-102, GP15-103 and GP15-104**) involving a total of 216 healthy volunteers, as well as data from a confirmatory efficacy and safety study of 531 patients with moderate-to-severe chronic plaque psoriasis (PsO) (GP15-302). The development program also included five non-clinical studies. The proposed indications for GP2015 are identical to the indications for Enbrel® in rheumatoid arthritis (RA), PsO, psoriatic psoriasis (PsA), ankylosing spondylitis (AS) and polyarticular juvenile idiopathic arthritis (JIA).

Phase III data shows Sandoz’ investigational biosimilar filgrastim has similar safety and efficacy as Amgen’s NEUPOGEN®.

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  • Pivotal PIONEER study compared safety and efficacy of the two compounds in the prevention of neutropenia in patients with breast cancer
  • PIONEER data supported filing for biosimilar filgrastim in the US
  • The abstract of the study results is published online as part of the 56th American Society of Hematology (ASH) Annual Meeting and Exposition

 

Holzkirchen, December 8, 2014 – Sandoz, a Novartis company, announced today Phase III data that demonstrated similarity of its investigational biosimilar filgrastim compared to the US-licensed reference product, Amgen’s NEUPOGEN ® (filgrastim) in the prevention of severe neutropenia in patients with breast cancer receiving neoadjuvant myelosuppressive chemotherapy. The study also showed that repeated switching at each cycle between the investigational biosimilar and the originator filgrastim showed no impact on efficacy, safety or immunogenicity.

 

The PIONEER study was a Phase III study designed to compare the efficacy and safety of the investigational biosimilar and the reference product with respect to mean duration of severe neutropenia following Cycle 1 chemotherapy. PIONEER was a randomized, double-blind, four-group, multi-center non-inferiority trial conducted at 27 centers. The trial randomized 218 breast cancer patients receivingneoadjuvant myelosuppressive chemotherapy.

 

On July 24, Sandoz announced that the FDA accepted its application for filgrastim, making Sandoz the first company to have a filing accepted under the new US biosimilar pathway created in the Biologics Price Competition and Innovation Act of 2009 (BPCIA). The Phase III PIONEER study results supported this filing.“Biosimilars can play an important role in broadening access to high-quality biologics in the United States,” said Prof. Kimberly Blackwell, MD, Professor of Medicine, Assistant Professor of Radiation Oncology, Duke University School of Medicine. “I’m also optimistic that the savings generated through the use of biosimilars can be used to fund other unmet medical needs.”

 

“We are pleased by these clinical study results as they confirm the similarity of our investigational biosimilar filgrastim compared to the reference product in terms of safety and efficacy,” said Mark McCamish, M.D., Ph.D., Head of Global Biopharmaceutical & Oncology Injectables Development at Sandoz. “The data from this important study also reinforces the results we have seen in earlier stages of development including multiple Phase I, pre-clinical and analytical studies. We look forward to making this product available to patients and healthcare providers in the United States.”

 

Sandoz is the global market segment leader with over 50 percent volume share of all biosimilars approved in North America, Europe, Japan and Australia.  Sandoz currently markets three biosimilars outside the US; each of which occupies the #1 biosimilar position in its respective category. Sandoz biosimilars are sold in over 60 countries and have generated over 170 million patient-exposure days in experience. Sandoz also has a robust pipeline with six molecules in Phase III clinical trials/registration – more than any other company in the industry.