The Center for Biosimilars

Anti—tumor necrosis factor biosimilars for the treatment of inflammatory disease present attractive cost savings for both payers and patients. A free, continuing education broadcast on September 29, 2020, at 8 p.m. will address the identification of patients most likely to benefit from biosimilars for inflammatory conditions, review current clinical evidence and real-world data on the use of these agents, and demonstrate how to develop evidence-based protocols for reducing expenditures and improving access to these treatments. This program is for managed care pharmacists and other interested clinicians and will be presented by Sonia T. Oskouei, PharmD, BCMAS, DPLA, vice president of Biosimilars for Cardinal Health. For more information or to register for the "Treating Inflammatory Conditions With Biosimilars" symposium, please click 

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A September 29, 2020, symposium with Sonia T. Oskouei, PharmD, BCMAS, DPLA, of Cardinal Health will explore how to incorporate biosimilars into the treatment of inflammatory conditions. 

Symposium: Treating Inflammatory Conditions With Biosimilars

The FDA has approved 28 biosimilar products, 16 of which have indications for patients with cancer. These include versions of the monoclonal antibodies trastuzumab, bevacizumab, and rituximab, as well as biosimilars for the supportive care agents pegfilgrastim, filgrastim, and epoetin-alfa.

Integrating biosimilars further into cancer care will require an educational outreach, according to Ali McBride, PharmD, MS, BCOP, clinical coordinator of Hematology and Oncology in the Department of Pharmacy at the University of Arizona Cancer Center and immediate past president of the Association of Community Cancer Centers (ACCC).

 with OncLive.com, he discusses the age of biosimilars, the ACCC’s initiative to broaden acceptance and use of these drugs, and the knowledge gaps that need to be filled to ensure biosimilars are properly understood.

Ali Mcbride, PharmD, MS, BCOP, is taking a lead role in promoting the use and understanding of biosimilars in oncology.

ACCC's McBride on the Need for Biosimilar Education

Having 5 trastuzumab biosimilars with indications for HER2-positive breast cancer or metastatic gastric or gastroesophageal junction adenocarcinoma illustrates the increasing role of these more cost-effective treatments.

Ruth O’Regan, MD, believes the evidence indicates these agents are similar in efficacy and safety to the originator drugs, and for this reason they should be employed more often by providers and patients.

In this way, the problem of financial toxicity can be diminished, said O’Regan, a professor of medicine in the Division of Hematology and Oncology at the University of Wisconsin School of Medicine and Public Health and associate director for Clinical Research at University of Wisconsin Carbone Cancer Center in Madison.

In a recent interview, O’Regan discussed access to biosimilars, the provider-patient conversation about using these drugs, and education issues that must be surmounted.

Currently, much of the power over drug choice belongs to payers, she said. “At the end of the day, we don’t make the decisions on which drugs to use.” She said she’s confident that payers will naturally be interested in biosimilars because they offer potential savings and, for this reason, biosimilars are going to become more and more available. She anticipates that at Carbone biosimilars are going to have a “very profound effect” on the costs of care.

For reasons of cost, it may be preferable to switch patients from more costly reference drugs to biosimilars. “They may be apprehensive to go on an alternative drug. However, we may have no option. We’re developing educational information for the patients so that they understand these drugs are essentially the same,” O’Regan said.

Knowing how to discuss biosimilars with patients is, therefore, important, she said. For starters, patients should be told that these drugs are the same, essentially, and that they cost less. Although biosimilars are intravenous formulations and look different from generic pills, for example, patients should know that there is no reason to believe that they wouldn’t be just as effective, she said.

“We need to reiterate that these drugs have been tested and they look exactly the same as the parent drug,” O’Regan said.

For patients just starting out with treatment, there’s likely to be less resistance to initiating with a biosimilar. “For patients with metastatic disease who are very dependent on [reference] drugs and have been doing well, it may be a little trickier.” In such an instance, bringing the pharmacist into the examination room to help explain that biosimilars are equivalent may be a useful strategy, she said.

The National Comprehensive Cancer Network (NCCN) has been a helpful advocate for biosimilars for several years now, O’Regan said. “This is very much on their radar. What the NCCN recommends will impact what is being done on a national level.”

Ruth O’Regan, of the University of Wisconsin Carbone Cancer Center, discusses improving the patient discussion on biosimilars, in an interview.
 

Carbone Professor: Biosimilars Have Important Role to Play

With 1 biosimlar launch and expanded indications for another biosimilar so far this year, Teva Pharmaceutical Industries has 

 higher biosimilar revenues for the first quarter of 2020 compared with the same time last year.

Biosimilar income helped to offset declines in revenue from generic products in the first quarter for Teva. For both categories, however, revenues were $952 million for the first quarter of 2020, which is down 1% compared with the first quarter of 2019.

The company attributed the decline to price erosion for its products and lower royalty income, offset by an increase in revenues from launches of new products, including the rituximab biosimilar Truxima. Revenues for Truxima were not disclosed.

Truxima was launched in November 2019 for the treatment of CD20-positive, B-cell non-Hodgkin lymphoma either as monotherapy or in combination with chemotherapy. Following the resolution of a patent dispute, the product became 

 this month for treatment of rheumatoid arthritis, granulomatosis with polyangiitis, and microscopic polyangiitis.

Overall, Teva's revenue for the first quarter of this year was $4.4 billion, which is an increase of 5% versus the year-ago quarter.

“Our very strong results during the first quarter of 2020 were impacted by greater demand in our major markets for generic and [over-the-counter] products and respiratory products,” said Kare Schultz, Teva’s president and chief executive officer.

The company reported net income for the quarter of $69 million, up from a loss of $105 million in the year-ago quarter.

In March of this year, Teva launched its trastuzumab product, Herzuma, in the United States. At present, the company has multiple biosimilars in preclinical and phase 1 development.

Teva has undergone a large-scale restructuring over the past 2 years, during which it sought to cut spending, reduce its workforce, and close manufacturing sites. For the quarter just ended, Teva said it had reduced its debt load by $600 million, leaving $24.3 billion in accounts payable.

With 1 biosimilar launch and expanded indications for another biosimilar so far this year, Teva Pharmaceutical Industries reported higher biosimilar revenues in the first quarter of 2020.

Teva Moves Further out of Debt and Gains Biosimilar Revenue

Eye health business Bausch + Lomb said it has entered into an agreement to commercialize in the United States and Canada a ranibizumab biosimilar candidate (Xlucane) currently under development.

The deal is with STADA Arzneimittel AG, of Bad Vilbel, Germany, and its development partner Xbrane, of Solna, Sweden. Xbrane announced 

 that it hopes to complete clinical trial enrollment for the age-related macular degeneration agent despite the limitations imposed by coronavirus disease 2019 (COVID-19) issues. Bausch + Lomb is headquartered in Laval, Canada.

The biosimilar references Lucentis, Novartis’ blockbuster drug, which loses its patent exclusivity in the United States this year and in Europe in 2022.

The partners in the biosimilar deal aim to obtain all currently approved indications for Lucentis. In the United States, the agent is approved for wet age-related macular degeneration, macular edema following retinal vein occlusion, and diabetic macular edema.

STADA and Xbrane will be jointly responsible for finalizing development of the biosimilar, and Xbrane will be the commercial supplier. Bausch + Lomb will handle the sales, marketing, and other commercialization efforts in both the United States and Canada, assuming regulatory approval is obtained.

“We believe that, once approved, this biosimilar ranibizumab candidate will be an excellent addition to our comprehensive eye health portfolio and further deliver on our commitment of continuing to expand and improve upon our ophthalmic portfolio for our customers and their patients,” said Yolande Barnard, vice president and general manage of US Pharmaceuticals for Bausch + Lomb, in a 

Company officials said they believe the biosimilar candidate has strong commercial potential in the North American marketplace. Indeed, Lucentis netted global sales of $2.1 billion in 2019.

COVID-19 has forced modifications in clinical trials to accommodate for patients’ inability to get to clinics. The danger of COVID-19 infections has also forced curtailment of some trial activities. However, Xbrane in April reported that it is on track toward approval of Xlucane ahead of the European expiration of Lucentis’ patent in 2022.

Bausch + Lomb has secured the rights to commercialize a ranibizumab biosimilar in the United States and Canada.

Bausch + Lomb Secures Commercialization Deal for Ranibizumab

Biosimilar competition took a big bite out of revenues for Amgen, although the company’s own biosimilar portfolio notched impressive growth, according to Amgen’s first quarter 2020 earnings. The company said the coronavirus disease 2019 (COVID-19) pandemic has caused a decline in new patient starts for some of the company’s products.

“Due to the uncertainty related to the COVID-19 impact, we expect some degree of uncertainty in quarterly revenue and earnings over the year. We currently expect that we will see the greatest impact later in Q2, with stabilization and then partial recovery occurring during the second half of the year,” said Peter Griffith, executive vice president and chief financial officer, during the company’s 

Amgen’s Neulasta (pegfilgrastim) sales declined 40%, to $609 million from $1 billion in the comparable year-ago quarter. There are 3 pegfilgrastim biosimilars on the US market: Ziextenzo, Udenyca, and Fulphila, by Sandoz, Coherus BioSciences, and Mylan/Biocon, respectively. Two of those were launched in 2019.

Neupogen (filgrastim) sales dropped to $65 million in the first quarter of 2020 from $73 million in the comparable year-ago quarter, an 11% decline. Neupogen has competition on the US market from the Pfizer/Hospira product Nivestym and Sandoz’ Zarxio, both biosimilars. Zarxio has been on the market since 2015.

Amgen’s epoetin alfa product (Epogen) had total sales of $155 million in the just-ended quarter, down from $219 million a year ago, representing a 29% decline. Marketed only in the United States, Epogen faces biosimilar competition from Pfizer/Hospira’s Retacrit, which launched in 2018.

The company reported first quarter 2020 sales of $1.2 billion for Enbrel (etanercept), roughly unchanged from $1.2 billion in the year-ago quarter. Amgen has so far managed to fend off biosimilar competition for Enbrel. Both Sandoz and Samsung Bioepis have FDA approvals for etanercept biosimilars but no announced launch dates. Sandoz has unsuccessfully 

 2 key patents that expire in 2028 and 2029, respectively.

Although some of its products are seeing serious sales erosion from biosimilar competition, Amgen is pleased with its own biosimilar portfolio, said Murdo Gordon, executive vice president of global commercial operations. “We continue to see encouraging adoption rates in clinics, with hospital adoption accelerating. These biosimilars are increasingly valuable given the cost savings they provide,” he said.

The company’s bevacizumab (Mvasi) and trastuzumab (Kanjinti) biosimilars generated $234 million in global sales during the first quarter.

, Mvasi had $115 million in total sales, up 37% from the fourth quarter of 2019. Kanjinti had $119 million in total sales, up 16 percent from a year ago.

In the United States, Mvasi had $108 million in sales in the first quarter, versus $79 million in the previous quarter. Kanjinti’s US sales were $96 million, up from $79 million the previous quarter.

Additionally, the US market shares for Mvasi and Kanjini were 33% and 27%, respectively.

“We're fortunate that we were early in the United States with both Mvasi and Kanjinti and able to establish a very strong foothold in the market,” said Gordon. Mvasi and Kanjinti were launched in the United States in July 2019.

Mvasi is a biosimilar for reference Avastin (bevacizumab) and is used to treat colorectal, lung, glioblastoma, kidney, cervical, and ovarian cancer. It is also used to treat age-related macular degeneration.

Kanjinti is a monocolonal antibody used to treat patients with HER2-postive breast cancer and stomach cancer. It is a biosimilar for reference Herceptin (trastuzumab).

In total, Amgen reported revenue of $6.2 billion for the first quarter, up 11% from the year-ago comparable quarter.  Despite that success, uptake of some products, notably Xgeva (denosumab), is being affected by the pandemic, the company said. “Certain products like Xgeva may be impacted in the current environment due to disruptions in physician-patient interactions,” Gordon said.

Gordon expressed Amgen’s intentions to launch Avasola, their biosimilar for Remicade (infliximab), on the US market sometime later this year, but did not specify a date.

“That product will help strengthen what is already a strong immunotherapy portfolio for us, and will help us broaden that customer perspective,” said Gordon.

Additionally, Amgen has an FDA-approved adalimumab biosimilar (Amjevita) to AbbVie’s reference drug Humira. However, due to AbbVie’s current patent exclusivity, Amgen will have to wait until 2023 to release it on the US market.

Amjevita is marketed in Europe and earned $86 million in first quarter sales, up from $31 million in the year-ago quarter. It is the most prescribed biosimilar adalimumab in Europe.

To sum up the current status of biosimilars, Gordon said, “I do think that the biosimilar market is alive and well in the United States and functioning as you would hope free markets would.”

Amgen saw biosimilar competition eat a larger share of its innovator drug revenue but also earned some biosimilar pocket money of its own.
 

Amgen Sees Biosimilar "Give and Take" 

Although the coronavirus disease 2019 (COVID-19) pandemic put a damper on activities, the month of April saw steady business developments, from biosimilar approvals and launches to strong earnings reports for biosimilars and even regulatory approval for a biosimilar manufacturing site.

With a growing portfolio of biosimilars, Novartis saw a 31% increase in biopharmaceutical 

 for the first quarter of 2020, despite the pandemic. Novartis develops and retails biosimilars through its Sandoz arm. Sandoz’ net sales for the quarter were $2.5 billion, up 9%.

 that biosimilar and generic competition are expected to hurt its originator brands this year to the tune of $2.4 billion in lost revenue, although it reported that its biosimilars portfolio is generating strong double-digit revenue growth.

 biosimilars earnings of $219 million for the first quarter, up 25% compared with the year-ago comparable quarter, an increase of $44 million. The company said its anti—tumor necrosis factor (TNF) biosimilars have been used to combat COVID-19 and it attributed $15 million of first-quarter earnings to this.

 that overall product sales increased 12% globally, and this included results for its bevacizumab and trastuzumab biosimilars, but the company said product revenues were offset by competition from other biosimilar and generic makers.

Shanghai-based Henlius Biotech said its Xuhui manufacturing facility has 

 for production of its trastuzumab biosimilar candidate, which the company said is “a passport” for potential commercialization across the globe. Anticipating approval of its trastuzumab biosimilar HLX02 from the European Medicines Agency, the company has put global commercialization plans into place.

Russia has rebuilt its pharmaceutical industry following the demise of the former Soviet-led government, and emerging companies such as Geropharm are looking for markets abroad. In an interview with The Center for Biosimilars

, MD, PhD, deputy director and head of clinical operations for Geropharm, said the barriers to biosimilar marketing in the United States are slowly diminishing, although in Europe the business opportunities are more robust.

 that the European Commission had approved its rituximab monoclonal antibody, Ruxience, for the treatment of non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, and other disorders.

 that it was launching its Ontruzant trastuzumab biosimilar in the US market. This became the third trastuzumab biosimilar to arrive on the US market in 2020, making the market more crowded for competitors. In this venture, Merck is the commercialization partner of Samsung Bioepis.

Sang-Jin Pak, MD, executive vice president of Samsung Bioepis’ Commercial Division, in an 

, said despite the growing competition for trastuzumab products, there is likely to be ample business opportunity.

 a pegfilgrastim biosimilar (Fulphila) in Australia, and on April 28, the companies announced they had 

 the same product in Canada, also. The agent helps to shorten the duration of severe neutropenia and reduce the incidence of infections, as manifested by febrile neutropenia.

 of biosimilar launches and approvals in the first quarter of 2020 with those in the comparable year-ago quarter showed more launches than FDA approvals in the just-finished quarter. Experts have said launch horizons for approved biosimilars can be expected to be pushed back 6 months or more, based on the complications presented by COVID-19 and the difficulties of marketing products in an environment where sales representatives cannot meet face-to-face with providers and other key individuals.

 could occur this year, experts said during the Academy of Managed Care Pharmacy (AMCP) virtual meeting in April. Those new products could include a pegfilgrastim, 2 bevacizumabs, and a rituximab.

COVID-19’s Effect on Biosimilar Business

An expert presenting for the AMCP virtual meeting 

 that COVID-19 notwithstanding, it’s important to keep the biosimilar pipeline active because of the important savings and access benefits these agents offer. “We are going to need specialty generics and biosimilars,” said Douglas M. Long, MBA, vice president of Industry Relations for IQVIA.

Finally, the FDA’s new focus on COVID-19 and the quarantines imposed on much of the developed world have pushed digital and remote marketing of pharmaceutical products into high gear, and this bodes well for a transformation in the way biosimilars are marketed in the United States, 

, managing director of iON, said in an interview with The Center for Biosimilars

A smattering of biosimilar launches around the globe and positive results for biosimilar earnings across companies suggested a positive trend in April, despite the ongoing pandemic.

Biosimilar Business Roundup: April 2020

In Europe, the Committee for Medicinal Products for Human Use (CHMP) has 

that marketing authorization be granted for a biosimilar insulin aspart developed by Sanofi and intended for the treatment of diabetes mellitus.

A final decision from the European Commission is pending.

CHMP said the product would be marketed as a solution for injection (100 units/mL). The active substance is insulin aspart, a fast-acting insulin analogue. In the body, this is absorbed more rapidly than human insulin and can therefore act faster.

The replacement insulin acts similarly to naturally produced insulin. It facilitates uptake of glucose into skeletal muscle and fat tissue and inhibits glucose output from the liver.

The biosimilar’s reference product is NovoRapid, which was authorised in the European Union on September 7, 1999. Data show that Insulin aspart Sanofi, the product’s brand name, has comparable quality, safety, and efficacy to NovoRapid, CHMP said.

The Committee for Medicinal Products for Human Use (CHMP) has given its recommendation for the marketing authorization of Insulin aspart Sanofi.

 Sanofi Insulin Biosimilar Gets CHMP Nod

German investigators had difficulty understanding why a Sandoz rituximab biosimilar was preferred over a Celltrion rituximab biosimilar in a 2-year retrospective study in clinics across the country; however, they concluded that providers were willing to use both of these products on an increasing basis to treat their patients.

“The affordability crisis in oncology is believed to be unsustainable,” said the investigators, who looked at the uptake of biosimilar rituximab beginning from its introduction in Germany in July 2017 through June 2019. They found that providers tended to stick with reference rituximab if that was the medication their patients had begun, but for patients newly started on therapy, providers tended to become more comfortable over time using biosimilars.

“A greater focus on value, alongside efficacy and safety, needs to be implemented across both healthcare systems and industry to prevent restricted access to life-saving treatments,” investigators wrote in their 

Although rituximab biosimilars have been on the market in Germany since 2017, the first rituximab biosimilar was 

 to the US market in November 2019, and this was at a discount of 10% to the reference product.

“Biosimilar and generic medicines provide 1 option to combat the increasing costs of cancer drugs. However, any improvements in sustainability afforded by biosimilars rely entirely on their uptake,” the investigators said.

Over the 24-month study, 38 rituximab-containing protocols were used 1540 times to treat patients with non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). This indicated a “high acceptance of biosimilars, even in extrapolated indications.”

Biosimilars were used in more than 50% of patients both in first-line and second-line or later treatment. The use of biosimilar rituximab grew 7-fold, driven mostly by an increase in Sandoz biosimilar rituximab prescriptions. Investigators were at a loss to explain why Sandoz became the preferred treatment versus the Celltrion biosimilar.

“From our data, it is not possible to explain this phenomenon; certainly, it was not driven by the list price, and there are few, if any, other differentiating factors between the 2 medicines,” the investigators wrote.

They speculated that the high cost of rituximab in general may have been the reason for the use of biosimilars. The Sandoz product was available for a discount of 11% to the reference product. They did not provide comparative price information for the Celltrion biosimilar.

Over the study period, the proportion of rituximab biosimilar prescriptions in the total patient population increased from 12% to 83%.

“Only a small number of switches were recorded in our study, suggesting that physicians generally maintain their original treatment choice. The switches that did occur included the entire gamut of possible changes, including reference medicine to biosimilar, between different biosimilar medicines, and from biosimilar to reference medicine,” the investigators said.

The authors concluded that more real-world study is needed “to evaluate the long-term effect of biosimilar rituximab on health economics, patient access, and the overall sustainability of cancer care.”

In the study, the most-frequent of the rituximab-containing therapeutic protocols used was bendamustine plus rituximab and rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisolone.  

A rituximab biosimilar was used in 55.2% of cycles overall, including 48.6% of cycles in patients with follicular lymphoma and 70.0% of cycles in patients with diffuse large B-cell lymphoma.

In those with NHL or CLL, a rituximab biosimilar was used in 52% of patients at first line and 55% at second line or later.

The reasons for biosimilar brand preference in a recent rituximab study were unclear, but investigators said it is clear that savings were a likely factor.

Investigators Ponder Sandoz Uptake Riddle

In the first quarter of 2020, the coronavirus disease 2019 (COVID-19) did not put a “material” crimp in the financial picture for Novartis, which 

 biopharmaceutical net sales, including biosimilars, of $450 million, up 31% from the comparable, year-ago quarter.

Novartis develops and retails biosimilars through its Sandoz arm. Sandoz net sales for the quarter were $2.5 billion, up 9%.

The company said much of its biopharmaceutical growth was driven by double-digit earnings in Europe, where the company has 8 biosimilars on the market. Novartis has 2 biosimilars on the market in the United States: Zarxio, a filgrastim product launched in 2015; and Ziextenzo, a pegfilgrastim, which was launched in November of 2019.  

 full-year 2019 global sales of biopharmaceuticals of $1.4 billion, up 27%, also largely fueled by growth in Europe and the United States. The 2 key drivers of that progress in Europe were the company’s rituximab (Rixathon) and etanercept (Erelzi) biosimilars. In the United states, growth was driven primarily by Zarxio. Sandoz has previously indicated high 

Overall, Novartis reported net sales of $12.3 billion for the first quarter of 2020, up 11% and representing net income of $2.2 billion, up 16%.

The company said its financial position was not materially affected by COVID-19. However, “COVID-19 did result in increased forward purchasing by customers, including at the patient level, as some patients filled prescriptions to cover a longer period of time,” Novartis said.

The company said it had implemented strong supply chain measures to mitigate disruption and provide for adequate inventory during the pandemic, and that it did not anticipate supply chain disruption “for the majority of the portfolio at this time.”

The company reported slowdowns in new patient enrollments in clinical trials and startups of new trials, although it said clinical trials are continuing and the company is closely monitoring more than 500 ongoing trials in 70 countries.

“At this time, we remain confident the impact on our ongoing clinical trials is manageable. Looking ahead for the remainder of the year, we do not expect delays in our planned 2020 regulatory submissions,” Novartis said.

In 2019, Novartis spun off its Alcon eye-care business and terminated a deal with Aurobindo Pharma to trade its Sandoz US generic oral solids and dermatology businesses.

In the United States, Sandoz has 2 approved-but-not-yet-marketed biosimilars: Hyrimoz, an adalimumab copy, expected to come to market in 2023; and Erelzi, an etanercept biosimilar, sales of which cannot move forward until patent issues are 

. Both of these are currently available in Europe.

The Sandoz biosimilar pipeline includes several candidates in phase 3 clinical trial development. These include a subcutaneous denosumab candidate for bone disease, intravenous trastuzumab for breast and gastric tumors, and intravenous natalizumab, a monotherapy for relapsed multiple sclerosis and Crohn disease.

In a 2019 interview with The Center for Biosimilars®, Sandoz’s Sheila Frame, MBA, vice president of marketing, market access, and patient services, and William Yoon, PharmD, MBA, head of external engagement and medical advocacy, 

 on the company’s progress and potential with biosimilars.

With a growing portfolio of biosimilars, Novartis saw a 31% increase in biopharmaceutical sales for the first quarter of 2020, despite the pandemic.