Tony Hagen is senior managing editor for The Center for Biosimilars

Tony Hagen

Under pressure from rival biosimilar manufacturers, Merck today 

 its US launch of the trastuzumab biosimilar Ontruzant at a 15% discount to the biologic medicine Herceptin.

 more than a year ago, in January of 2019, and joins 4 other trastuzumab biosimilars now on the US market.

Ontruzant is the third trastuzumab biosimilar and the fourth biosimilar overall launched on the US market since the beginning of 2020.  The launch occurs during a challenging time for pharmaceutical companies, which have had to ground field sales representatives because of the coronavirus disease pandemic and rely more heavily on digital and telecommunications to promote their products.

Pfizer and a Celltrion/Teva partnership both introduced trastuzumab biosimilars in the first quarter of this year.

Ontruzant is the 17th biosimilar to launch in the United States, which has 26 approved biosimilars.

The biosimilar is available in both 150 mg single-dose vials and 420 mg multiple-dose vials. Ontruzant was introduced at wholesaler acquisition cost (WAC) of approximately $1325 for the 150 mg single-dose vial and $3709 for the 420 mg multiple-dose vial. WACs do not include discounts to payers, providers, distributors, and other purchasing organizations.

The agent is indicated for adjuvant treatment of 

overexpressing node-positive or node-negative breast cancer as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; as part of a treatment regimen with docetaxel and carboplatin; or as a single agent following multimodality anthracycline-based therapy.

The biosmilar was launched by Merck as part of a development and commercialization agreement with Samsung Bioepis. Samsung Bioepis is responsible for preclinical and clinical development, process development and manufacturing, clinical trials and regulatory registration. Under the agreement, Merck will be responsible for all commercialization activities for products approved in its partnered territories, including the United States.

On February 5, 2020, Merck announced that it intends to spin-off products from its women’s health, trusted Legacy Brands and biosimilars businesses, including Ontruzant, into a new, independent, publicly traded company. Merck will support the commercialization of the biosimilar until the spinoff, which is expected to occur in the first half of 2021, at which time Ontruzant will become a product of the new company.

The other trastuzumab biosimilars are Kanjinti, which launched in July 2019; Ogivri, December 2019; Trazimera, February 2020; and Herzuma, March 2020.

Articles

In partnership with Samsung Bioepis, Merck has launched the trastuzumab biosimilar Ontruzant, which marks the fifth trastuzumab biosimilar available on the US market.
 

Merck Follows Rivals With US Launch of Trastuzumab Biosimilar 

The first quarter of 2020 saw 3 biosimilars brought to market in the United States, 2 of them from Pfizer, and no new approvals from the FDA. That compares with 1 launch and 2 approvals in the year-ago quarter.

The year began with robust stock market performance and a much-touted partnership between the FDA and the Federal Trade Commission to clamp down on anticompetitive practices by pharmaceutical companies looking to block biosimilar competition. But the unforeseen happened in the form of the coronavirus disease 2019 (COVID-19) pandemic, which has significantly shifted priorities at the FDA and caused some developers of biosimilars to also shift their efforts toward developing treatments for COVID-19.

Experts have said launch horizons for approved biosimilars can be expected to be 

 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.

Among the biosimilars brought to market in the first quarter of this year was Pfizer’s version of rituximab, Ruxience, in January. Ruxience is 

 for the treatment of non-Hodgkin lymphoma, chronic lymphocytic leukemia, granulomatosis with polyangiitis, and microscopic polyangiitis. The product received its FDA approval in July of 2019. Pfizer said in a statement that despite the pandemic, commercialization of the product has moved forward with a combination of field sales rep activity and other forms of promotion.

Pfizer also launched a trastuzumab biosimilar, 

, in February of this year. The agent is indicated for the treatment of HER2-overexpressing breast cancer, in the adjuvant and metastatic settings, and HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma. The biosimilar was initially approved on March 11, 2019, a full year after its approval.

That product was quickly followed to market by another trastuzumab biosimilar, Herzuma, which was the result of a partnership between Celltrion and Teva. FDA approval for the agent was granted in December of 2018, and Herzuma made it to market in March of this year, roughly 14 months later. Herzuma is 

 for the treatment of patients with HER2-overexpressing breast cancer in both the adjuvant and metastatic settings.

There are currently 5 trastuzumab biosimilars that have FDA approval, and all 5 are on the market, as of April 15, 2020, when Merck launched its Ontruzant trastuzumab biosimilar.

The fifth, Ontruzant, by Samsung Bioepis, is available in Europe and will be 

 in the United States by Merck. No launch date has been announced.

For all of 2019, there were 7 biosimilar launches in the United States and 10 FDA biosimilar approvals.

The promise of biological agents in the United States is illustrated by the tremendous share they command among all medicinal agents in the marketplace. Biologics currently represent 42% of medicine sales, up from 30% in 2014, according to a March 2020 

 by IQVIA. The respective dollar totals for biologics are $85.5 billion versus $144.5 billion.

The appeal of launching biosimilars is in the potential earnings. Biogen and Genentech have reaped a windfall of $51 billion from their rituximab originator product, from launch to September 2019, according to IQVIA.

IQVIA estimated that 50% of biologics market sales could face biosimilar competition if all approved biosimilars in the United States were actually launched.

The first 3 months of 2019 saw a trio of biosimilar launches on the US market, ahead of the year-ago quarter's pace, and this came despite the disruption caused by coronavirus disease 2019.

 

Pfizer Leads With 2 First Quarter Biosimilar Launches 

 suggests that the patent blockade preventing adalimumab biosimilars from reaching market in the United States is hugely expensive for consumers and the healthcare system.

By switching to biosimilar adalimumab, the Danish healthcare system was able to slash costs by 82.8% and sustain that for more than a year, even though use of adalimumab significantly increased over the same period.

In the United States, patent battles have 

 the arrival of biosimilars to reference adalimumab (Humira) until 2023. However, in Denmark where AbbVie’s exclusivity for adalimumab expired in October 2018, the Danish Medicines Council immediately switched to biosimilars for all indications of the reference product. The country also switched patients who were already using the reference agent.  

Prior to October 2018, Denmark used Humira exclusively, at a cost that averaged $5 million per month. For the year ending October 2019, biosimilars were used almost exclusively and per-month costs consistently hovered close to the $1 million mark.

Also prior to AbbVie’s loss of exclusivity in Denmark, the country was using roughly 8000 prefilled syringes (pens) of reference adalimumab each month. From October 2018—the point of exclusivity loss&mdash;to October 2019, use of adalimumab pens increased to roughly 13,000 per month, with only a very small fraction of those pens being the originator product.

“Access to generic and biosimilar drugs is generally needed to ensure market competition and lower drug prices,” wrote the authors of the Danish study. They noted that many factors may prevent the use of biosimilars in the United States, including lack of automatic substitution of agents, drugs not being included on formulary, and manufacturers withdrawing discounts on originator drugs if payers use biosimilars (rebate traps).

The authors noted that AbbVie had US market net revenue of $3.9 billion from Humira in the third quarter of 2019. The drug is the world’s top-selling medicine, with $19 billion in annual revenue in 2018.

“Thorough preparation and multidisciplinary collaboration between all stakeholders were key points in the Danish implementation, and they are crucial for successful implementation in the United States,” the authors wrote.

They said it is possible that by the time reference adalimumab loses exclusivity in the United States, in 2023, the window of opportunity for biosimilars of this product may have closed, because 

 may have picked up market share from Humira.

“The lack of adalimumab biosimilars results in substantial premiums being paid by patients and payers when much cheaper biosimilar drugs are available outside the United States,” the authors wrote.

The Denmark health system used 3 adalimumab biosimilar brands, 1 for pediatric patients and 2 for adult patients, following discontinuation of Humira use.

Costs of adalimumab dropped 82.8% from September 2018 to December 2018 (September, 8197 pens at $5.13 million; December, 9438 pens at $1.01 million). The proportion of biosimilars used in December 2018 was 77.9% (438 of 562 pens) for pediatrics, 94.7% (4348 of 4590 pens) for adults in Western Denmark, and 97.7% (4188 of 4286 pens) for adults in Eastern Denmark.

The authors said there were no significant differences in proportions of biosimilars used between dermatology, gastroenterology, and rheumatology.

The Danish medical system saved 82.8% on adalimumab by switching almost all patients from the reference product to biosimilars, but such a benefit for the US healthcare system may not be possible, according to a new study.

AbbVie Patents Are Costly for Healthcare Consumers

BiosanaPharma has announced successful completion of a phase 1 clinical study for a biosimilar to omalizumab, which in the United States is FDA approved for the treatment of asthma and chronic idiopathic urticaria and marketed as Xolair.

BiosanaPharma, a biotech with operations in Australia, The Netherlands, and Singapore, said the study of biosimilar candidate BP001 in healthy volunteers (N = 84) demonstrated bioavailability, safety, tolerability, and immunogenicity similar to what has been shown by reference omalizumab.

 supports further clinical development of BP001. The company added the next step will be a phase 3 study comparing BP001 with the originator in patients with allergic asthma. This study scheduled to begin in early 2021.

Xolair, marketed by Novartis and Roche since 2006, is the only approved product containing omalizumab. BiosanaPharma hopes to carve out a portion of the annual sales of Xolair, which it estimated at $3.2 billion in 2019. Xolair is delivered via subcutaneous injections.

The company may find itself with plenty of competition if its product makes it to market.

Celltrion also hopes to grab a share of the Xolair market. In July of 2019 the company announced plans to start a phase 1 

 of the omalizumab biosimilar candidate CT-P39.

Glenmark Pharmaceuticals completed a phase 1 trial of an omalizumab biosimilar (GBR 310) in 2018. Results indicated similarity to the reference product, the company 

Also, Sorrento Therapeutics is developing 

, a biosimilar to the omalizumab reference product.

Omalizumab lost patent protection in the United States in June 2017, and in Europe in August 2017. Novartis is fighting back against encroaching challenges. It won FDA approval in 2018 for a pre-filled syringe formulation of omalizumab; and Novartis has worked to expand 

BP001 is produced using what BiosanaPharma described as the world’s first continuous process for manufacturing monoclonal antibodies (mAb), which the company contends can reduce production costs by up to 90%.  

“We are very proud that we now have successful phase I results for our first biosimilar product. This validates our use of fully-continuous manufacturing for biologics and allows us to move forward in our quest to deliver low-cost mAb biosimilars,” said Ard Tijsterman, chief executive officer of BiosanaPharma.

Omalizumab is an antibody targeted toward free Immunoglobulin E (IgE); it is used to improve the control of severe persistent asthma that is caused by an allergy, and chronic spontaneous urticaria in patients with elevated IgE who do not respond to treatment with antihistamines.

BiosanaPharma has developed what it calls a proprietary “3C” technology platform that is highly productive and flexible and able to produce 1 kg of drug antibody per week at a 50 L bioreactor scale. The manufacturing process is continuous. This, the company said, has the potential to make biosimilars and other products more affordable.

The omalizumab biosimilar candidate is the company’s first product.

“At BiosanaPharma, we believe in rationalizing the market for mAbs and mAb biosimilars. The key parameter to achieve this goal is costs, and the winning strategy will be to reduce costs, from manufacturing to distribution,” the company 

With positive phase 1 study results and a manufacturing process that may cut costs significantly, BiosanaPharma hopes its omalizumab biosimilar candidate will have an edge on the worldwide market.
 

BiosanaPharma Reports Positive Phase 1 Results for Omalizumab Biosimilar 

The coronavirus disease 2019 (COVID-19) has swiftly changed priorities in the healthcare industry, and in some cases, activities have come to a grinding halt.

For pharmaceutical companies that had ambitions to launch biosimilars and other drug products this year, major revisions of sales strategy may have become necessary, according to Jamie Peck, 

 of iON, a digital services arm of the healthcare marketing company Indegene, which is based in India with offices in Princeton, New Jersey.  

Field sales reps have been sidelined by COVID-19 quarantines, leaving companies to figure out other ways to get the message out about new products.

“A lot of companies have reached out to us and said ‘How can we get through this? What can we do to keep our reps engaged with physicians?’” Peck said.

And further, companies are cognizant that in a post—COVID-19 world, the sales game may be an entirely different creature that cannot be herded back into a traditional model. “They’re asking what they can put into place long term, because they have this sense that things are not going to get back to where they were pre-pandemic,” Peck said.

The biosimilar launch pad saw a handful of products positioned for marketing in the first quarter of 2020. Among them were 

 by Pfizer: Ruxience, a rituximab product; and Trazimera, a trastuzumab biosimilar.

A Pfizer spokesperson said the company has handled those launches with a combination of field reps and other forms of promotion.

“We have launched our biosimilars with a committed field force and will also be offering broad educational resources and support services to patients and physicians,” said the spokesperson, Jessica Smith, who said Pfizer declined to comment further on its commercialization strategy.

Large companies are in a boat of their own in this pandemic, Peck said. They have size and resources to their advantage. In this group, Sandoz, Biocon, and Pfizer number among clients that iON/Indegene have worked with.

“They’re not necessarily worried about this as much from an immediate, acute business need. They have security. We’ve already talked to them before about how to use digital in their launches,” Peck said.

Smaller companies may have more at stake. Among the general pharma companies that Peck advises is one that had aspirations to launch a product in July. It had a spring 2020 PDUFA, or Prescription Drug User Fee Act, date, “which by all indications will probably get pushed back by the FDA,” owing to COVID-19 preoccupations. This, in turn, will push back the launch, he said.

It’s the company’s first launch, and so it’s important to members of the board and to investors to see it comes off on schedule and successfully. “They hired several hundred reps to do this, and they stopped the hiring process. They’re planning now on moving the entire launch to a digital platform,” Peck said.

Bluebird bio is another example of a medium-size biotechnology company that has been caught in the middle of the COVID-19 storm, Peck noted.

“Generally, the company expects the COVID-19 pandemic to shift the timing of enrollment and completion of clinical studies by at least 3 months,” bluebird bio said in a March 26 

COVID-19 issues have delayed interaction with the FDA on product applications, and a launch of Zynteglo, a treatment for β-thalassemia, was planned for January 2020 but “given the evolving COVID-19 situation, the company expects the treatment of the first commercial patient in Germany to be shifted to the second half of 2020,” bluebird bio said.

The FDA has given priority to COVID-19 matters, which leaves it short of attention for routine matters, observers say. Peck agreed. “The bandwidth at the FDA is creating scenarios where some of these companies may not be able to hang around and wait for their product. Their investors and their boards may get impatient and they just may run out of runway. They don’t have the safety cushion that big pharma has,” he said.

Although this is the new reality for pharma, it has been a long time coming. With the rise and reach of digital marketing, such as email blasts, telemarketing, and artificial intelligence systems that can dig for sales prospects and eliminate wasted effort by human sales reps, the role of the sales rep has diminished steadily over the past 15 years. According to ZS, the number of 

 numbered just over 101,800 in 2005 and descended to 68,400 in 2017.

Concurrently, access to physicians has declined. The percentage of physicians described as “accessible” to sales reps dropped from 65% in 2012 to 44% in 2016, also according to ZS.

Accessibility varies widely according to specialty. For example, urologists were the most accessible, at 77%, according to the ZS report. Rheumatologists came in second, at 68%. Neurologists were 54% accessible, and oncologists were just 17% accessible. The old days of being able to spend quality time with a physician are gone. Instead, physicians get much of their information from digital channels, and reports indicate they are often more comfortable receiving data this way than from salespeople.

iON/Indegene markets what it calls an “omni-channel” constellation of services that include heavy emphasis on smart technology and digital reach. The ongoing pandemic is going to prove or disprove the concept of a vastly reduced salesforce supplemented by digital, Peck says. “It’s really going to be a test of our model, which says you may not need 500 reps; you may need 50. It’s going to be a real test to see whether can we do this.”

The FDA’s new focus on coronavirus disease 2019 (COVID-19) and the quarantines imposed on much of the developed world have pushed digital and remote marketing of pharmaceutical products into high gear, according to Jamie Peck, managing director of iON.

COVID-19 Will Test Digital Marketing of Pharmaceuticals

Longtime generic drug manufacturer Lannett said it would 

 with the FDA June 9, 2020, to plan the next steps for clinical advancement of its planned insulin glargine biosimilar. Insulin glargine is a long-acting insulin used to treat adults with type 2 diabetes and adults and pediatric patients with type 1 diabetes.

Under a March 23, 2020, change in the approval pathway for insulin products, insulin glargine is now considered a biologic and must be reviewed under section 351 of the Public Health Service Act. Lannett, of Philadelphia, Pennsylvania, is developing the insulin product in a partnership with the HEC Group of companies.

Tim Crew, chief executive officer of Lannett, 

 the meeting with the FDA is expected to result in specific guidance that will clarify the requirements for a successful biologics license application.

"We expect our discussion with the FDA to include the design and endpoint of any additional human studies required for filing a Biologics License Application (BLA) and approval of insulin glargine as a biosimilar," he said.

In December 2019, Lannett announced positive 

 from the first human study evaluating insulin glargine. The company said that in terms of pharmacokinetics and pharmacodynamics, the trial confirmed that the Lannett/HEC biosimilar insulin glargine is equivalent to the reference product Lantus. Lannett said the study met all primary end points.

"With the positive data from this human clinical trial, combined with the earlier comparative analytical assessment and animal studies, we are building certainty around our development program," Crew said at that time.

Kristin Arnold, PhD, Lannett’s vice president of research and development, said the biosimilar insulin candidate product was safe and well tolerated, with no serious adverse events or serious drug reactions observed during the study.

Lannett, founded in 1942, develops, manufactures, packages, markets, and distributes generic pharmaceutical products for a wide range of medical indications.

Longtime generics manufacturer Lannett is moving an insulin glargine biosimilar development plan forward and announced an upcoming meeting with the FDA. The agent would compete with the reference product Lantus.

Lannett Will Discuss Insulin Glargine Application With FDA

Aware that travel restrictions and border controls imposed by coronavirus disease 2019 (COVID-19) pose a threat to drug supply, the International Generic and Biosimilar Medicines Association (IGBA) is working to establish priority designations for medicines in air and sea cargo transport.

The move is among diverse attempts by private and public institutions recently to secure supplies of drugs and pharmaceuticals amid the dizzying pace of events. “The situation is constantly and rapidly changing,” said Suzette Kox, secretary general of IGBA, in an interview with The Center for Biosimilars

In recent days, many have spoken out against export curbs and other protectionist measures that threaten to upset the balance of international healthcare. Some actions by governments have involved instating emergency powers to bypass patent exclusivity protections where necessary.

On March 25, the Canadian legislature passed an emergency bill that would allow that country to circumvent patent laws to ensure adequate supplies that are needed to respond to the COVID-19 public health emergency.

And White House administration trade advisor Peter Navarro recently 

that the administration was planning to order federal agencies to prioritize purchasing US-made drugs and medical supplies.

The IGBA contends that any restrictions on the export of pharmaceutical products are counterproductive. “We will work toward keeping global markets open, and our industries are focusing right now on meeting the increasing demands. We also see encouraging signs of international commitments, collaboration, and coordination to support the movement of medicines,” Kox said.

 called for governments gobally to establish priority designation for medicines at custom controls and for cargo and freight. The priority would include goods needed to manufacture these agents.

“There is an absolute urgency to facilitate and speed up the movement of essential products at all levels, in particular at customs control, as well as systematically reserve cargo capacity for those products in air/sea cargo, which are vital partners in delivering much-needed essential goods,” the group said in a release.

Trade groups and consumer advocates are working to fight the rising tide of protectionism generated by the coronavirus disease 2019 pandemic. The International Generic and Biosimilar Medicines Association (IGBA) is calling for dedicated air and sea channels to keep pipelines of essential medicines open between borders.
 

IGBA, Others Oppose Protectionist Actions Amid COVID-19

Stymied in its attempts to move forward with construction of a $514 million biosimilars manufacturing facility in Wuhan, China, the origin of the coronavirus disease 2019 (COVID-19) outbreak, Celltrion is trying another business strategy that may tide it through the current global economic crisis: It has joined the hunt for an antiviral treatment for the coronavirus.

”By screening blood sourced from recovered patients in Korea, Celltrion has secured 300 potential antibody candidates to treat COVID-19, and work is underway to select the therapeutic antibodies that are most effective at neutralising the SARS-CoV-2, the virus responsible for COVID-19,” a company spokesperson said.

The race to find therapies effective against COVID-19 has attracted major pharmaceutical players. This week, Amgen, a large player in the biosimilars market, 

 that it has partnered with Adaptive biotechnologies to develop human neutralizing antibodies targeting SARS-CoV-2. Amgen and Adaptive said they are finalizing financial details of the deal.

Celltrion is well along in this endeavor, having completed the initial phase of securing antibodies that show signs of being able to target SARS-CoV-2.

Celltrion expects this phase of the investigation to be complete by mid-April, after which “the most promising antibody will form the basis of a therapeutic antibody treatment that encourages production of antibodies that recognise and block the spike protein that the virus uses to enter human cells,” the spokesperson said.

“Once we have selected the one that most effectively neutralizes the COVID-19 virus among hundreds of the screened antibodies, we will roll out mass production of the therapeutic antibody treatment, with a view to starting human trials this July,” Ki-Sung Kwon, head of research and development at Celltrion, said in a release.

The company has said it remains strongly committed to construction of the Wuhan plant, for which an April groundbreaking had been forecast. But given the threat of the virus and the growing lockdown on movement, those development plans are on hold.

“While we remain strongly committed to the project, we are closely monitoring the situation and will continue to communicate with the officials of Hubei province,” a spokesman said earlier this week.

Investigation has ramped up across the pharma sector in response to the COVID-19 pandemic. Besides antibodies, companies are investigating repurposed antivirals and RNA interference, which involves blocking protein translation by selective degradation of its encoded messenger RNA.

Meanwhile, Amgen said it is working rapidly and using high tech to expedite progress on the COVID-19 front.

“After swiftly obtaining viral gene sequences from hundreds of patients, Amgen was motivated to use these insights and quickly pair them with our drug development and manufacturing capabilities. Working with Adaptive and using their viral-neutralizing antibody platform will expedite our ability to bring a promising new medicine into clinical trials as quickly as possible,” said Robert A. Bradway, chairman and chief executive officer at Amgen, in a statement.

The race to find a way to knock down the coronavirus disease 2019 pandemic has attracted companies with stakes in the biosimilar game. The winner could take all.

Celltrion, Amgen Join Race to Develop SARS-CoV-2 Antibodies

After a few years struggling with quality issues at its new Malaysia plant, Biocon appears to be closer to getting its insulin glargine (Semglee) product on the market in the United States. The company announced that the FDA noted only voluntary improvements needed on the latest inspection of the facility.

This follows earlier receipt of Complete Response Letters and Form 483 notices, which indicate that essential improvements are needed to allow production.

The resolution of those issues and the just-announced plant clearance represent “an endorsement of our commitment to global standards of quality and compliance,” the company said in a release.

The latest inspection, in February 2020, appears to have come under the wire for Biocon, as in March the FDA announced that it would suspend foreign site inspections as a result of the coronavirus 2019 (COVID-19) pandemic.

“The inspection has been closed with a Voluntary Action Indicated classification in the Establishment Inspection Report,” Biocon said in a release.

“The closing of the USFDA Inspection of our Malaysia facility is an important milestone in our journey of developing insulin glargine for patients in the United States,” Biocon said.

The company has partnered with Mylan in the effort to bring the biologic to market. Mylan has previously filed an application for the product with the FDA under the 505(b)(2) new drug application pathway under the FD&C Act. Under a change in the Biologics Price Competition and Innovation Act, insulin applications will be reviewed as biologic license applications under section 351 of the Public Health Service Act.

The insulin glargine product is already authorized in the European and Australian markets, where it is sold under the brand name Semglee.

In 2019, the Malaysia plant received a certificate of good manufacturing practice from the European Medicines Agency’s Irish inspection authority.

The effort to get the Malaysia plant approved for production was the result of a manufacturing site change from Bangalore.

After a number of issues raised by the FDA about plant quality, Biocon has gotten clearance for its Malaysia insulin plant and now awaits FDA marketing authorization for Semglee, its insulin glargine agent.
 

FDA Clears Biocon's Insulin Factory in Malaysia

Multiple Canadian provinces aim to switch patients to biosimilars, in a sweeping effort to save money for pubic health, and the transition has provoked much comment, not all of it enthusiastic.

At least 4 of Canada’s 10 provinces—Ontario, Alberta, British Columbia, and Manitoba&mdash;have now announced intentions to switch patients to biosimilars from reference products.

Critics argue the change to a policy of nonmedical switching will adversely affect patient care and lead to higher long-term healthcare costs, according to a 

The cost-savings appeal of switching to biosimilars is evident in Alberta’s projections for reductions in expense: up to US $268 million over the next 4 years. The province will have switched at least 26,000 patients by the summer of 2020.

 that the cost of biologic drugs are going up an average of 16.2% each year, and “the originator biologic drugs Remicade [infliximab], Humira [adalimumab] and Enbrel [etanercept] are 3 of the top 4 drivers of drug spending in Alberta.”

In that province, patients will be switched from the reference biologics for etanercept, infliximab, insulin glargine, filgrastim, pegfilgrastim, and glatiramer.

Biologics have been shown to be effective in inducing remission and avoiding surgical interventions, not to mention improving quality of life for patients.

Anti-tumor necrosis factor therapies are the single highest expense for patients in the Canadian healthcare system, at a cost of US $14,132 annually for each patient, the report said. However, the Canadian Association of Gastroenterology and Crohn’s and Colitis Canada 

 in a position paper that their evidence review supports a position against nonmedical switching from reference infliximab to biosimilars in patients with stable inflammatory bowel disease (IBD).

 authors note that even reference biologics differ from batch to batch, but such high standards are applied to the manufacture of these and biosimilars that “they are just as safe and effective.”

The authors cite Mina Mawani, president and chief executive of Crohn’s and Colitis Canada, who contends the nonmedical switch from reference product to biosimilar introduces variability that “is irresponsible and may jeopardize these patients’ health.”

Another issue raised is that some infusion centers in Canada have exclusive contracts with specific pharmaceutical companies and may not be available for infusion of biosimilars. This may require patients to switch centers and travel long distances for treatment, causing infusion centers to become overwhelmed with patients, according to critics.

The Canadian Association of Gastroenterology and Crohn's and Colitis Canada also contend that “1 patient may lose response to infliximab for every 11 patients undergoing nonmedical switching. Applying this data to the Alberta IBD population, this could lead to 63 avoidable surgeries if all Albertans on Remicade [infliximab] are switched to a biosimilar.”

Canadian provinces encounter opposition in their move to implement forced switching of patients from reference products to biosimilars.