Skylar Jeremias

STADA Arzneimittel and its partner Xbrane Biopharma said their ranibizumab biosimilar candidate (Xlucane) has demonstrated comparable efficacy to the originator (Lucentis) in a phase 3 clinical trial.

“We welcome this important step toward bringing a high-quality, cost-effective treatment option to ophthalmologists and their patients,” said Bryan Kim, global head of specialties at STADA, in a 

The positive trial results come after STADA 

 its bevacizumab biosimilar, Oyavas, in Germany and The Netherlands in April 2021 for the treatment of colon, rectal, breast, epithelial ovarian, fallopian tube, cervical, primary peritoneal, and non-small cell lung cancers.

Ranibizumab is a vascular endothelial growth factor inhibitor used to treat wet age-related macular degeneration (wAMD) and diabetic macular edema.

The randomized, double-masked, multi-center study assessed the pharmacokinetic properties, safety, efficacy, and immunogenicity of the biosimilar in patients with wAMD. In total, 583 patients with wAMD were recruited for the study and randomized to receiving monthly injections of the biosimilar or the reference product for 1 year.

from Xbrane, the patients were recruited from 140 clinics in 15 countries.

During the Xplore clinical trial, the biosimilar met the primary end point of equivalent efficacy in best corrected visual acuity after 8 weeks of treatment. Furthermore, there were no clinically meaningful differences between the drugs as measured by pharmacokinetic, immunogenicity, and safety profiles at 6 months.

Xbrane said it will collect additional data on secondary end points during the summer of 2021 and the complete dataset is expected to be published in a scientific journal or presented at a scientific conference as early as 2022.

STADA and Xbrane entered a codevelopment agreement for the biosimilar in July 2018 and per the terms of the agreement, will contribute equally to the development costs and share the profits after approval and marketing. STADA will oversee sales and marketing of the biosimilar in Europe and the companies’ commercialization partner Bausch + Lomb will be responsible for marketing in North America.

Xbrane and STADA are expected to submit an application for marketing authorization in Europe in the third quarter of 2021 and a Biologics License Application to the FDA during the fourth quarter of 2021, according to Xbrane.

“With ranibizumab, STADA’s growing biosimilars presence would extend beyond oncology, nephrology, osteoporosis, and autoimmune indications into the multi-billion-euro eyecare market. We look forward to continuing to work closely with our partner Xbrane on applying for regulatory approval of our biosimilar candidate in major markets,” said Kim.

If Xlucane is approved by European regulatory officials, it may have to compete alongside Samsung Bioepis and Biogen’s ranibizumab biosimilar, Byooviz (SB11), which recently 

 a positive recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use late last month.

STADA Arzneimittel is headquartered in Bad Vilbel, Germany, and Xbrane Biopharma is based in Stockholm, The Netherlands.

Articles

Early study results indicate that STADA Arzneimittel and Xbrane Biopharma’s ranibizumab biosimilar is as safe and effective as the reference product, suggesting regulatory approval may be on the horizon. 

STADA, Xbrane Ranibizumab Candidate Meets Primary End Point in Phase 3 Trial

, a bevacizumab biosimilar developed by Stada Arzneimittel, in Germany and the Netherlands. The product launched immediately after receiving regulatory approval from the European Commission for the treatment of several types of cancer. Stada said it plans to launch Oyavas in other European countries once it receives national pricing and reimbursement clearance.

Additionally, Bio-Thera Solutions and Biogen announced they are 

 to commercialize a tocilizumab biosimilar candidate, BAT1806, for the treatment of rheumatoid arthritis. Under the partnership, Biogen will have exclusive rights to market the biosimilar outside China in exchange for a $30 million up-front payment.

 to file a new drug application for its checkpoint inhibitor candidate, HLX10. The candidate will not be labeled as a biosimilar despite being comparable to pembrolizumab and nivolumab at treating microsatellite instability–high and mismatch repair–deficient solid tumors. The company is also developing bio-better products, which function as improved versions of originator drugs, and combination therapies featuring biosimilars.

 with Russia-based Pharmapark for HD204, Prestige’s bevacizumab biosimilar candidate. HD204 is currently being tested in a phase 3 trial and is under review with the European Medicines Agency. The biosimilar will be produced at Prestige’s factory in the Republic of Korea, and Pharmapark will have exclusive distribution rights throughout Russia.

 during the first quarter of 2021, reporting earnings increases resulting from the adoption of their respective biosimilar products. For Q1 2020 to Q1 2021, Amgen reported a 156% increase in sales for its bevacizumab biosimilar (Mvasi) and Teva reported a 26% increase in market share for its rituximab biosimilar (Truxima).

Merck said in its earnings report that biosimilars and women’s health spinoff company 

 stands likely to achieve $6.1 billion in revenue in 2021. In June 2021, Organon will begin operating as an independent publicly traded company.

, according to the company’s first quarter 2021 report. Earnings erosion for Roche comes as a result of biosimilar competitors for blockbuster reference drugs Rituxan (rituximab), Avastin (bevacizumab), and Herceptin (trastuzumab). Avastin sales dropped 40% from the same quarter in 2020, and Rituxan saw a 37% decline. Herceptin sales also dropped, although not as dramatically, and Roche did not specify exactly how much, stating only that a basket of products for oncology including Herceptin saw an 11% sales decline.

Boehringer Ingelheim said that its adalimumab biosimilar, Cyltezo, is on track to 

 interchangeable biosimilar in the United States. The product performed well during a phase 3 switching study in patients with plaque psoriasis, showing comparable safety and efficacy. To demonstrate the equivalency needed for an interchangeable rating, patients in the trial were switched between the reference product and the biosimilar multiple times.

Samsung Bioepis became the most recent recipient of the International Forum Design Award for its 

. The packaging features soft shapes and soothing mono-colors, with the company describing the concept as “Passion for Health—Pure Joy in Life.” This is the company’s second international award for its packaging designs.

PlantForm, a Canadian biotech company, said it will initiate a program to 

 to cultivate antibodies that will be used to develop a pembrolizumab (Keytruda) biosimilar for the Brazilian market. PlantForm uses tobacco plants instead of animal cells to develop antibodies to help them avoid some of the production complexities posed when using animals and bioreactors.

Biosimilar companies partnered with other companies and saw earnings increases, while reference product corporations faced sales erosion from biosimilar competition.

Biosimilar Business Roundup for April 2021

Based on the success of a biosimilar switching program, Nedzad Pojskic, PhD, MSc, vice president of Pharmacy Benefits Management for Green Shield Canada, detailed why payers should become bigger advocates for biosimilar uptake, at the Festival of Biologics USA meeting.

Canada ranks third in the world in per capita spending on drugs ($1012 vs $1324 in Switzerland and $1457 in the United States), he said, explaining the need for biosimilar savings.

“I think it's really important to recognize that as payers in this country, we have to be explicit around being leaders in educating various stakeholders, whether they be physicians, other sorts of players in the system, patients, or those in leadership roles, to support a viable biosimilar market and to move forward,” said Pojskic.

 have begun executing biosimilars switching initiatives, Pojskic noted that Green Shield Canada was the first payer to have a policy that preferred biosimilars to originators.

Under the program, patients with a number of rheumatic conditions are either started on or switched to biosimilar versions of infliximab, etanercept, and rituximab, whose respective originator brands are Remicade, Enbrel, and Rituxan. Other biosimilar switches are expected with future program expansions.

Pojskic said that, for him, one of the most important lessons to come out of implementing a biosimilar transition program such as this was that payers are the real “gatekeepers” to biosimilar uptake.

“Evidence has shown us time and again that when payers allow open access to an originator and a biosimilar with no preferential policies for biosimilars, the uptake naturally flows to the originators….However, with more aggressive policies that target a sustainable biosimilar market and the uptake of biosimilars in preferential fashion, we start to see payers being a really important part of this equation,” he said.

When biosimilars and originators are treated equally on the formulary, patients and providers flock to originator products because they have historical comfort with using the dominant brands. As a result, biosimilar uptake occurs very slowly, Pojskic said.

So far, Green Shield Canada’s program is a success, generating an average of $8500 in savings per member annually.

Of the patients involved in the program, 55% transitioned to a biosimilar and 14% stayed on the originator but were billed for the price of the biosimilar, which resulted in reduced costs, Pojskic noted.

Pojskic also said that Green Shield Canada made it a priority to work with patients to ensure comfort with biosimilar switching, and this was successful. He reported that patients understood and were receptive to the change, had talked with their physicians about transitioning, and appreciated the support and aid given by nurses.

The Canadian health care system primarily functions as a Medicare-like structure that covers most aspects of hospital and physician care. However, pharmaceuticals are different in that they are funded both privately and publicly. Canada spent $39.8 billion on drugs in 2018, and of that, $12.30 billion and $14.33 billion was privately and publicly funded, respectively, and out-of-pocket costs for pharmaceuticals were $13.10 billion, Pojskic said.

The share of total pharmaceutical costs generated by biologics spending 

 year-over-year, from 20% in 2015 to 24.7% in 2019. Pojskic said that

number to grow as more biologics enter the market.

As biosimilars have entered the market, discounts from originator costs have ranged from 17% for filgrastim biosimilars to 50% for some infliximab biosimilars, he said 

Canada is one of the largest purchasers of originator infliximab, but at the end of 2018, uptake of infliximab biosimilars was only at 8% of total use, slightly above the United States (7%) but significantly trailing Norway (98%), Poland (96%), the United Kingdom (92%), Austria (89%), and Italy (79%), according to Pojskic’s presentation.

everal factors pose barriers to biosimilar uptake in Canada:

There are no interchangeability policies (pharmacists cannot simply substitute biosimilars without physician approval)

Payer policies offer reimbursement for biosimilars without making them preferred products

Switching to biosimilars was not encouraged until recently

Originator manufacturers interfere with biosimilar uptake

Pojskic said a major hurdle that had to be overcome when implementing the biosimilar transition program was addressing the common concern that there is not enough evidence to support the safety of biosimilar switching.

To combat this, Green Shield Canada produced a systematic review of studies showing that switching between originators and biosimilars was safe and effective. The review encompassed 178 studies, of which 140 were based on real world evidence, and included data on 21,000 patients and 10 biologic agents.

“There's plenty of evidence to support biosimilar transitioning and it all points in exactly the same direction. We knew that this evidence was more than enough to safely engage in biosimilar transitioning and to create a program,” said Pojskic.

To overcome provider and patient preferences for brand originators, there has to be more of an incentive to use biosimilars, explains Nedzad Pojskic, PhD, MSc, Green Shield Canada.

Green Shield Canada: Preferential Status Is Vital to Biosimilar Uptake

During March, both state and federal legislators moved forward with bills to increase access to biosimilars, biosimilar advocacy organizations made changes to their guidelines, and experts criticized current and proposed policies that they said would not improve biosimilar uptake.

 a bill requiring the FDA to provide the public with educational information that is supportive of biosimilar adoption. The Advancing Education on Biosimilars Act was introduced in 2019 and was initially voted on in December 2020 but required a fresh vote for 2021.

Under the bill, the FDA would develop a biosimilars education website that would include information on key statutory and regulatory terms used in reference to biosimilars, including 

. The website also would be tailored to the needs of health care providers and would make comparative data for originators and biosimilars available.

Also, Minnesota state legislators introduced a bill aimed at 

 to biosimilars by requiring health plans and pharmacy benefit managers to cover all versions of a biologic equally—biosimilars and originator products. The bill would create more opportunity for biosimilars to compete alongsideoriginators by denying payers the ability to make formulary decisions in favor of more costly biologics.

In an interview with The Center for Biosimilars®, Maria Manley, LLM, a life sciences expert, discussed the hoops pharmaceutical companies 

 to ensure that their products could still be marketed in the United Kingdom after the country’s official departure from the European Union, which was dubbed Brexit.

In light of Brexit, many companies had to transfer product marketing authorizations from UK entites into EU entities to ensure that their products were properly domiciled. Brexit also led to the establishment of a free trade agreement without tariffs or quotas between the United Kingdom and European Union.

In a March webinar sponsored by the Biologics Prescribers Collaborative, a 

 discussed former president Trump’s proposed Most Favored Nations policy, which was intended to change the reimbursement structure of Medicare Part B drugs to lower drug costs. This was frowned on by the panel because it would prevent an estimated 9% of Part B patients from having access to their medications.

The methodology behind the Institute for Clinical and Economic Review’s value assessments for drugs was also criticized by the panel. They argued that the assessments are based solely on clinical trial data and are conducted prior to drugs receiving FDA approval, making the assessments less representative of how drugs would perform in real-world settings.

Additionally, a white paper noted some reasons that biosimilars are currently 

 for the health care system. The authors pointed to CMS’ policy of allowing originators and biosimilars to have separate reimbursement codes and prices under Medicare Part B. The authors argued that the policy conflicts with the agency’s goal of fostering a competitive market for biologics.

Place generic drugs in Medicare Part D on generic formulary tiers with lower cost-sharing than brand name drugs

Ensure Medicare beneficiaries have access to new generics

Update Medicare Part D to include a dedicated specialty tier for generics and biosimilars

Reward Medicare health plans for encouraging use of lower-cost generics or biosimilars and eliminating barriers to access

End brand “rebate traps” that prevent use of generics and biosimilars

Increase the Medicare Part B add-on payment to providers who use biosimilars

Encourage adoption of biosimilars with a shared savings program

Repeal or amend the Medicaid drug price inflation penalty for generics

In other news, the Association for Accessible Medicines published a position paper that detailed a 

 for CMS to change some of its policies. Some of the policy changes suggested were rewarding Medicare plans that encourage use of generics and biosimilars, ending “rebate traps” that prevent access to generics and biosimilars, and increasing add-on payments for physicians who prescribe biosimilars.

The National Comprehensive Cancer Network released a 

 advising health care providers to lobby for policies that avoid payer formulary preferences and create more access to biosimilars. The guidelines also addressed issues regarding biosimilar procurement and the need to stock multiple biosimilars of the same drug, which is costly and leads to errors.

 Michel Robidoux, the president and general manager of Sandoz Canada, as chair of the trade association’s board. In a statement, Robidoux praised the successes of British Columbia and Alberta’s biosimilars initiatives that require patients with chronic conditions to be switched to certain biosimilars as a mode of creating savings on biologic spending.

The month of March brought intense debate and legislative action over biosimilar policies. 

Skylar Jeremias

STADA, Xbrane Ranibizumab Candidate Meets Primary End Point in Phase 3 Trial

Biosimilar Business Roundup for April 2021

Green Shield Canada: Preferential Status Is Vital to Biosimilar Uptake

Biosimilar Policy Roundup: March 2021