Tony Hagen is senior managing editor for The Center for Biosimilars

Tony Hagen

Biocon Biologics, of Bengaluru, Karnataka, India, reported first-quarter revenues were up 26%, to $275.9 million, vs the comparable year-ago quarter, driven largely by the company's biosimilars, research services, and generics businesses.

Amid the resurgence of COVID-19 in India, the company has also seen an increase in demand for itolizumab (Alzumab), which has shown value in treating acute respiratory distress syndrome (ARDS) associated with COVID-19.

First-quarter biosimilar revenues were $89.6 million, up from $59.8 million a year earlier, representing a 53% improvement, the company said. Total net income was $34.7 million, up 95% from a year earlier.

During the just-ended quarter, Biocon received marketing authorizations from the European Commission for a bevacizumab biosimilar (Abevmy) and an insulin aspart biosimilar (Kixelle). Biocon also received approval from the World Health Organization (WHO) for its trastuzumab biosimilar (Ogivri) in the 150 mg and 420 mg formulations. A WHO approval is generally referred to as a “prequalification” and represents the WHO’s thumbs-up for product quality and manufacturing practices.

In a statement, Arun Chandavarkar, managing director of Biocon, said improved sales in the company’s biosimilars segment were characterized by revenue growth in emerging markets and market share gains for the company’s pegfilgrastim and trastuzumab biosimilars in developed markets. The company also noted revenue gains for its insulin glargine product (Semglee), which was introduced in the United States in August 2020 and for which the company is seeking biosimilar status.

Itolizumab, an IgG1 kappa anti-CD6 monoclonal antibody, received 

 in India in July 2020 for the treatment of cytokine release syndrome in patients with moderate-to-severe ARDS who were hospitalized with COVID-19. Originally launched in India for the treatment of chronic plaque psoriasis, the drug reduces T-cell infiltration at sites of inflammation without depleting T cells or B cells.

In its most recent earnings statement, Biocon said at least 6500 patients were treated with itolizumab in April 2021. In March, the company published 

 from a randomized phase 2 study of the safety and efficacy of itolizumab in patients with moderate-to-severe ARDS due to COVID-19.

Investigators found itolizumab improved the 1-month survival rate and lung function, with reduction in the need for ventilator or respiratory support. They concluded “

Itolizumab is a promising, safe and effective immunomodulatory therapy for treatment of ARDS due to cytokine release in COVID-19 patients, with survival and recovery-benefit,” although further study was recommended and this was in accord with earlier published research that recommended a go-slow approach.

Celltrion Group, another biosimilar developer, reported promising 

 for the use of regdanvimab (CT-P59) in the treatment of 3 variants (K417N, E484K, and N501Y) of the South African COVID-19 mutation (B.1.351). The company said CT-P59 

 a significant reduction in viral load of SARS-CoV-2. Enrollment of 1300 patients in a global phase 3 clinical trial to evaluate the efficacy and safety of CT-P59 has been completed. 

“We are encouraged by the new data, which reinforces that Celltrion’s CT-P59 treatment could be effective against the South African variant and variant mutations,” said HoUng Kim, PhD, head of the Medical and Marketing Division at Celltrion Healthcare.

Articles

Biocon tests the waters with itolizumab in pandemic-ravaged India, and Celltrion announces early success with an agent for the South African variant. 

Reports From Biocon, Celltrion on Finances, COVID-19 Treatments

Biosimilars producers reported positive sales trends for biosimilars as the pandemic wears on and said patients still are not visiting doctors in the proportions they did before the start of the health crisis in early 2020. 

 for biosimilars and noted mixed results for legacy brands that face biosimilar competition. In all, the company said revenues dropped 4% to $5.9 billion for the first quarter of 2021 vs the comparable 2020 first quarter. COVID-19 sales trends were partly to blame for this. Amgen reported net income of $1.6 billion, down 10% from last year’s first quarter.

First-quarter sales of the bevacizumab biosimilar Mvasi were up 156% from this time last year ($294 million vs $115 million). Amgen reported higher sales volume but a lower net selling price. Mvasi has a 50% share of the bevacizumab market in the United States, and Amgen expects to launch in multiple markets worldwide going forward.

Sales of the trastuzumab biosimilar Kanjinti were up 35% compared with the first quarter of 2020 ($161 million vs $119 million). Again, higher volume was offset by a lower net selling price. The US share of the trastuzumab market for this product is 43%.

Amgen saw sales of its adalimumab biosimilar (Amgevita) rise 23% this past quarter vs the comparable 2020 quarter ($106 million vs $86 million). However, sales growth appears to have flattened, climbing just 3% since the fourth quarter of 2020.

Originator brands at Amgen that face biosimilar competition had sales declines. Enbrel (etanercept) revenues dropped 20%, from $1.15 billion in the first quarter of 2020 to $924 million, the result of sales volume declines and a lower net selling price. The company said it expects this downward trend to continue.

Sales of pegfilgrastim (Neulasta) dropped 21% over the past year, from $609 million to $482 million, the result of selling price and volume declines caused by biosimilar competition. The Neulasta Onpro, a wearable injector device, maintained a 54% share of the pegfilgrastim market in the first quarter “and continues to be the preferred choice for physicians and patients,” Amgen said. However, the company reported that the most recent average selling price for Neulasta in the United States was down 30% over the past year and 9% over the past quarter.

Sales of the filgrastim originator Neupogen were down 48% over the past year, the result of volume declines caused by competition, Amgen said.

For a detailed Amgen drug-by-drug slide presentation, click 

, Merck, of Kenilworth, New Jersey, has reiterated expectations for at least $6.1 billion in 2021 revenue for its planned biosimilars and women’s health products spinoff Organon.

Organon was acquired from Shering-Plough in 2009 and will be an independent company on June 2, 2021, with public trading set to begin June 3, 2021. Merck has stated that in spinning off Organon, it expects to achieve operational efficiencies of $1.5 billion spread over 3 years. 

The biosimilars unit that is part of Organon generated roughly $250 million in 2019, and Merck has not been consistent about reporting biosimilars revenues since then. Merck has partnerships with Samsung Bioepis of Incheon, Republic of Korea, to market infliximab (Renflexis), trastuzumab (Ontruzant), and etanercept (Brenzys, Eticovo) biosimilars. Organon generates 75% of its sales revenue from markets outside the United States.

For more reading about Merck and its biosimilars spinoff, click 

, Teva Pharmaceuticals of Tel Aviv, Israel, reported a 26% US market share for its biosimilar rituximab (Truxima), which is also in the European Union. Overall company revenues dropped 9% to $3.98 billion.

The company attributed the drop to lower sales for over-the-counter, generic, and respiratory products, among other product declines. Strong sales were reported for Austedo (deutetrabenazine), for tremors, and Ajovy (fremanezumab), for migraines. No actual revenue information was provided for Truxima, which was launched in 2017 in the European Union by Celltrion and in 2019 in the United States by Teva and Celltrion.

There's no end in sight for Enbrel (etanercept) sales erosion, but Amgen's biosimilars are holding their own, the company reported.

Amgen, Merck, Teva Provide First-Quarter Biosimilars Info

Boehringer Ingelheim believes it is on its way toward gaining perhaps the first interchangeable designation for a biosimilar, based on 

, a phase 3 randomized study that compared pharmacokinetic properties for the adalimumab reference product (Humira, RP; 40 mg/0.8 mL) with those of the adalimumab biosimilar Cyltezo (BI 695501) in patients with moderate-to-severe chronic plaque psoriasis.

Patients received RP continuously or switched between the biosimilar and RP, and investigators concluded that patients who were switched multiple times between RP and Cyltezo experienced similar clinical outcomes in terms of pharmacokinetics, efficacy, immunogenicity, and safety.

“This study is, to our knowledge, the first to report outcomes that meet the US FDA’s criteria for interchangeable biologic designation,” investigators stated in findings presented at the American Academy of Dermatology 2021 virtual meeting this month.

There are 29 FDA approved biosimilars but none of them has an interchangeable designation, meaning that, depending on individual state laws, pharmacists could fill prescriptions with biosimilars rather than the originator product without approval from the prescribing physician. It is generally assumed that the lack of interchangeable designations is a chief impediment to patient and physician confidence in biosimilars, which are FDA approved as being “highly similar” to originator brands, and just as safe and efficacious, with no clinically meaningful differences.

For an interchangeable designation from the FDA, a biosimilar is “expected to produce the same clinical result as the reference product in any given patient” and “not present greater risks in terms of safety or diminished efficacy from alternating or switching between the interchangeable candidate and reference product,” Boehringer Ingelheim noted, quoting from FDA guidelines.

Cyltezo was approved in 2017 and is scheduled for launch on July 1, 2023, based on a settlement with AbbVie. Boehringer Ingelheim anticipates an FDA decision on the application for interchangeability in the fourth quarter of 2021.

In VOLTAIRE-X, investigators evaluated area under the curve (AUC), or drug concentration over time in the bloodstream; Cmax, or peak concentration after administration of the first dose; presence of anti-drug antibodies (ADAs), a measure of immunogenicity and the body’s response to adalimumab; and presence of neutralizing antibodies (nAbs), which can diminish or boost biosimilar effectiveness.

They randomized 238 patients to the switching (n = 118) or continuous treatment (n = 120) arms. In the switching and continuous treatment cohorts, the adjusted mean AUC was 2025.83 μg.h/mL vs 1925.90 μg.h/mL, respectively (ratio of adjusted means, 105.19%; 90.2% CI, 96.58-114.64).

Adjusted mean Cmax was 7.08 μg.h/mL and 7.00 μg.h/mL in the switching and continuous arms, respectively (ratio of adjusted means, 101.14%; 90.2% CI, 93.26-109.70). Investigators concluded the 90.2% CIs for AUC and Cmax were within the acceptable bioequivalence boundaries of 80% to 125%.

In the evaluation for immunogenicity, investigators found that at week 32 similar proportions of patients had developed ADAs in the switching vs continuous treatment arms (90.2% vs 94.5%, respectively), and nAb results were similar also between the 2 arms (41.1% and 41.8%, respectively).

In the switching vs continuous treatment arms, the proportions of patients who achieved a psoriasis area and severity index (PASI) score of 75 (75% or better showing improvement over baseline PASI scores) were also similar: 84.7% vs 79.0%, respectively (90% CI, –2.45%-13.96%).

The proportions of patients with physician global assessment (PGA) scores ≤1 at week 32 were also similar between the switching and continuous treatment arms: 70.3% vs 64.7%. The PGA is 5- to 6-point measure for disease severity.

On safety, investigators noted that following randomization, the percentages of patients who experienced at least 1 treatment emergent adverse event (TEAE) were similar in both arms (56.8% and 62.5%, respectively). A slightly higher percentage of patients experienced drug-related TEAEs in the continuous treatment arm (18.3% vs 11.9%).

Menter A, McCabe D, Lang B, et al. Phase III, randomized trial comparing clinical outcomes between patients with moderate-to-severe chronic plaque psoriasis receiving adalimumab reference product continuously versus those who switched between BI 695501 and adalimumab RP. Presented at: American Academy of Dermatology 2021; April 23-25, 2021. 

The results of Voltaire-X could persuade the FDA to authorize automatic substitution of the adalimumab biosimilar Cyltezo for its reference product (Humira), investigators believe. 

Cyltezo Is a Contender for First Interchangeable to Humira, Boehringer Ingelheim Says

Two much-touted bills for biologics and biosimilar advancement went to President Joe Biden’s desk for signing recently and were approved, but the devil is in the details, and whether they are going to have a tangible effect on biosimilar access is debatable.

The legislation changes the language of the Federal Food, Drug, and Cosmetic Act and urges greater efforts by federal regulators to educate the public about biosimilars, often a lower-cost alternative to originator biologics. “The Ensuring Innovation Act and the Advancing Education on Biosimilars Act of 2021 are a much-needed boost to help normalize use of biosimilars, just as generics were normalized years ago,” 

 chief medical officer of the pharmacy benefit manager Prime Therapeutics, which has successfully pushed for greater biosimilar use among its prescription drug plan participants.

The language of the education bill states that “The Secretary,” presumably the FDA, will work to “advance education and awareness” of biologics and biosimilars among health care providers. This would involve the creation of education programs on prescribing biologics. The new law also provides that the government “may” maintain and operate a website to provide educational materials for health care providers, patients, and caregivers about biologics and biosimilars.

There’s potential in the education bill in that it states that education efforts “shall” be directed at providers, said Chris Betti, PhD, an intellectual property attorney with Morgan Lewis specializing in biologics litigation. However, the act is “largely symbolic” because the FDA established a 

 in 2018 and that included the goal to educate providers and the public about biosimilars.

In addition, the act is heavily reliant on patients’ willingness to independently search out information about biosimilars and fill in any gaps by themselves. Simply dangling a website out there for patients may not have the desired effect, Betti said.

The Ensuring Innovation Act has its roots in efforts to break through originator biologic patent barriers that may prevent biosimilar developers from bringing their drugs to market, but in its approved form it isn’t capable of advancing that mission, Betti said. Patent thickets—clusters of patents created to protect the exclusivity of originator biologics—are likely to prove immune to the Ensuring Innovation Act. 

This law has more value when it comes to clearing patent obstacles that hinder the emergence of small-molecule chemical compounds, otherwise known as generics, Betti said. “In the legislative history of this particular bill, there was a lot of discussion back and forth about biologics and what can be done about patent thickets. This bill does nothing to address biosimilars. Rather, it’s very narrowly focused on small molecules,” he said.

The legislation changes the language of the Federal Food, Drug, and Cosmetic Act so that the words “active ingredient” are replaced with “active moiety.” This restricts the additional patenting that can be done when an originator company builds up a core drug compound with new active ingredients. Compounds are not biologics, though, as biologics are developed from living organisms. “This change has no effect on the biosimilars market and no effect on the exclusivity that is already given to biologics,” Betti said.

Patent thickets have the power to block biosimilar market entry from multiple angles, and addressing this is “not something that can be addressed by a very simple piece of legislation such as this. Some pretty substantial changes to the Patent Act would be required,” he said.

How much muscle did Congress invest in a pair of bills recently signed by President Biden? The answer may lie in your willingness to believe. 

Toothful or Toothless? Biden's Biosimilar Bills Under the Microscope

An ongoing real-world observational study of bevacizumab biosimilar (Mvasi) vs originator (Avastin) has demonstrated comparable safety and effectiveness for a cohort of patients with metastatic colorectal cancer (mCRC) treated in a US integrated health care system (Kaiser Permanente), according to a poster presentation at the Academy of Managed Care Pharmacy (AMCP) 2021 meeting. 

Patients were enrolled in the study based on initiation of biosimilar bevacizumab between July 1, 2019 and March 30, 2020 (n = 232) or initiation of bevacizumab reference product between July 1, 2015 and June 30, 2018 (n = 1128).

The primary end point was overall survival (OS) and mortality, and secondary end points were treatment persistence, defined as the total number of doses received, time between first and last dose, and the proportion of patients who switched to the reference product. Other secondary end points were the incidence of serious adverse events (SAEs) and hospitalizations and emergency department visits of any type.

Investigators said OS for the bevacizumab biosimilar cohort (82.8%) was noninferior to that of the reference product group (81.7%), based on a 4% margin of acceptability. They said that between the 2 groups, there were no significant differences in treatment persistence, SAEs, or hospitalizations and emergency department visits.

They said the study successfully captured real-world outcomes for patients treated with bevacizumab biosimilar immediately after the product was launched. They also said a strength of the study was its use of a large historical control group. Limitations of the study included that it was observational, which is not considered as reliable as a clinical study, and that it had a relatively short follow-up period, investigators said.

Pham C, Chiu T, Ekinci E, et al. Real-world evaluation of biosimilar bevacizumab-awwb versus bevacizumab in patients with metastatic colorectal cancer in a U.S. integrated healthcare delivery system. Presented at: AMCP 2021; April 12-16, 2021. Accessed April 23, 2021. https://amcpannual2021.pathable.co/organizations/7nYnTLzA3j3JZpccw#/?limit=10&sortByFields[0]=isPinned&sortByFields[1]=lastActivityAt&sortByOrders[0]=-1&sortByOrders[1]=-1&uid=pAcLoMw6BXog7ypr6

Investigators tapped health system data to conduct an observational, real-world comparison of bevacizumab (Mvasi) vs the reference product (Avastin). 

Kaiser Permanente Study Demonstrates Equivalence for Mvasi

Medicinal packaging doesn’t have to be harsh and strident. That’s the concept behind the biosimilar packaging for which Samsung Bioepis continues to earn international awards. Most recently, Samsung Bioepis has garnered International Forum (iF) Design Award 2021 honors for packaging.

Soft shapes and soothing mono-colors characterize the package designs for Samsung Bioepis’ drug products, which include biosimilars. The company, based in Incheon, Republic of Korea, has called its package design concept “Passion for Health—Pure Joy in Life.”

“Taking medication can be a constant reminder of the medical condition, and we wanted to remind patients of ‘pure joy’ in life when they look at our product packaging and design,” Jaywoo Kim, senior vice president and manufacturing division leader at Samsung Bioepis, said in a 

The company won in 2 categories: Packaging—Medicine/Pharmaceutics and Communication—Corporate Identity/Branding. 

In 2020, the company won package design awards in the 

Medicinal packaging shouldn't remind patients that they have a condition, according to Samsung Bioepis.

Samsung Bioepis Racks Up More Awards for Its Biosimilar Packaging

It’s going to be an issue for accessibility of medicine if competing companies won’t produce biosimilars of drugs that aren't as lucrative as biosimilars of blockbuster medicines, a panel of European experts said at the Medicines for Europe Biosimilar Medicines Virtual Summit 2021.

“It’s well known that development costs of biosimilars are very high compared with the development costs of generics,” said moderator Adrian van den Hoven, director general of Medicines for Europe. “Are we, in Europe, going toward a market where biosimilars will be up only against very big blockbuster biologics, whereas the smaller, more medium-size biologics won’t be worthwhile?” he asked.

In Denmark, the market for biosimilars is small (population 6 million), and yet there has been robust interest from biosimilars developers. Health authorities have to be careful not to get into a situation where prices are too low that companies might withdraw their bids to supply biosimilars, said Dorthe Bartels, senior strategic advisory at Amgros, the national procurement organization for Denmark. 

However, she said, a positive sign is that in China many companies are developing biosimilars for a broad range of biologics that are not limited to the most lucrative of biologics. 

Given the high cost of developing biosimilars, manufacturers might have minimum sales revenues requirements, which could preclude them from producing biosimilars for relatively minor indications, said Phillip van Wilder, a professor at Université Libre de Bruxelles School of Public Health in Belgium. This issue is connected to the problem of sustainability of biosimilars and needs to be part of the general discussion, “because it’s something where resilience is necessary,” he said.

Europe may be perceived as a place where biosimilars have in general been widely accepted, compared with the United States, and yet biosimilar success varies across EU member states. Panelists discussed the value of “top down” approaches to impose the use of biosimilars where market dynamics appear not to be working.

The European Union as a whole cannot force the use of biosimilars on member states, but it can influence biosimilar uptake via recommendations issued to countries that receive money from the European Union, van den Hoven said. “Many EU countries are now in the situation where they are receiving recommendations from the [European Commission], so should the commission be recommending or telling member states “you should have more biosimilar competition in your market?” he asked.

Bartels said that based on the Denmark experience, it might be better to use an education approach to communicate to stakeholders the gains that have been achieved by using biosimilars. For example, in Denmark, the country has achieved an initial 85% discount on the cost of originator adalimumab. “In the rheumatoid arthritis area, around 15% more patients have gained medicine, because we have introduced biosimilars, so maybe the story should be around the success of introducing biosimilars and the treatment for patients,” she said.

Have conversations with physicians and patients about switching to biosimilars and provide information that supports this education and influences behavior.

Use a top-down policy approach that provides a structure for biosimilar uptake.

Plan everything over time so everybody is prepared, because then you have people with you instead of against you. And you can do things regionally, nationally, or even in just one hospital.

Use a holistic approach that incorporates biosimilar company contracts (tenders), hospital finances, communication, and quotas.

A somewhat authoritarian policy that imposes biosimilar uptake could be of value in some Central Europe countries where biosimilar competition has not evolved as hoped, said panelist Tomas Tesar, an associate professor of pharmacy with Comenius University in Slovakia. There tends to be segmentation in these markets where originator biologics end up not competing head-to-head with biosimilars. “These are issues which could be solved by a top-down approach,” Tesar said.

Biosimilars have been approved as monotherapies for various indications, but more and more, pharmaceutical companies are developing combination medicines, and the panel viewed this as an opportunity to channel more biosimilar use, because these combinations of 2 or more drugs, which end up getting approved by regulators, could include 1 or more biosimilars from the get-go. The use of biosimilars has the potential to bring down the cost of these combination therapies. “We’ve seen in some countries, mainly in the United Kingdom, that expensive innovator compounds used in combination with biosimilar versions are cost-effective and are therefore accessible to the patients,” van den Hoven said.

This is happening in Denmark, Bartels said. Biosimilar use is written into applications for marketing of biologic combinations. “I think that’s actually the way forward. It will be cheaper for all of us.”

Combining innovator products with biosimilars as a concept appealed to other members of the panel. However, “we need to find a policy in which there is at least some competition in the market between various providers of the same products,” van Wilder said.

European countries have tender systems that allow drug companies to bid to obtain near exclusive license to supply drugs, although countries also work with multi-tender agreements that allow more than 1 supplier. In Denmark for adalimumab, although it is a small country, the tender was awarded to 2 bidders because of concerns that a single supplier might not be able to supply the whole market consistently. For now, that’s the only multi-supplier arrangement in Denmark, Bartels said, but it’s possible it might be tried with other drugs.

Europe has biosimilars approved for 17 different originator drugs, and another 30 innovator biologics are expected to lose market exclusivity over the next 10 to 15 years, according to IQVIA. Van den Hoven asked the group to speculate whether or not the next wave of biosimilars can be incorporated into practice with greater ease than the ones that came before.

Ireland is still on the beginning end of the biosimilar adoption curve, said Bernard Duggan, a chief pharmacist with Trinity Centre for Health Sciences at St James’ Hospital in Dublin. “We’ve come a long way in the last 2 years.” That experience likely could make uptake of the next series of biosimilars much swifter, he said. “I supposed we’ve learned a lot as we’ve gone through the process. It’s not one-size-fits-all. There will be slight nuances that need to be considered, but I think we have a framework here now that, if we’re called upon again, could be used to promote further uptake of other biosimilar medicines.”

The European Union is a diverse market with pockets of biosimilar resistance but also cost-saving triumphs, panelists said at the Biosimilar Medicines Virtual Summit 2021.

Medicines for Europe Panel Tackles Biosimilar Uptake

New Brunswick, Canada, a province of roughly 780,000 people, has become the third Canadian province to 

 that mandates the use of money-saving biosimilars for patients with inflammatory diseases.

“Increasing the use of biosimilars is expected to save over $10 million once fully implemented and the savings will increase as more biosimilars become available,” said Department of Health Minister Dorothy Shephard. “Biosimilars have been proven to work just as safely and effectively as biologic drugs. Savings from increasing their utilization will be reinvested to support coverage of new therapies and improve patient access to more medications.”

New Brunswick follows British Columbia and Alberta in switching patients to biosimilars. Officials said that in New Brunswick biologic drugs are among the largest drug expenditures and are growing. From 2019 to 2020, spending on biologics there rose 19% to $51 million. “In the same year, biologic drugs accounted for 29.4% of drug costs but only represented 1.5% of the total number of prescriptions paid,” officials said.

They said about 3000 patients currently under treatment for arthritis, diabetes, inflammatory bowel disease, and psoriasis will have until November 30, 2021, to switch from originator biologics to biosimilars, based on consultations with their physicians.

“This biosimilars initiative follows similar policies implemented by British Columbia and Alberta over the past 2 years, where tens of thousands of patients in each province were safely switched from an originator biologic drug to a biosimilar. Switching to biosimilars has also been conducted extensively in Europe, where countries have had over 15 years of experience with biosimilars,” the statement said.

Officials with the Department of Health said they consulted with multiple stakeholders on the switch to biosimilars, which was endorsed by prescribers and patient groups including Arthritis Consumer Experts, Arthritis Research Canada, Arthritis Society, and the Canadian Digestive Health Foundation.

“Biologic medicines have revolutionized the treatment of many disabling and life-threatening diseases but it can cost $10,000 to $25,000 or more to treat a patient with a biologic drug for a year, which is placing an enormous financial strain on drug budgets,” said the Candian biosimilars trade group Biosimilars Canada in applauding the move.

British Columbia recently announced it would switch patients to 

Following the lead of British Columbia and Alberta, New Brunswick, a heavily forested province located between Nova Scotia and Quebec, hopes to save on biologics. 

New Brunswick, Canada, Switches Patients to Biosimilars

Biosimilars took a $1.74 billion bite out of revenues for Roche, the company said in its first-quarter financial report, contributing to an overall sales decline of 1% from January to March 2021. This stiff competition from biosimilars was not unanticipated, Roche said. However, the company hit milestones with new product sales and sees a rebound as pandemic effects are mitigated. 

“The uptake of our recently introduced diagnostic tests and medicines remains strong, while we continue to see the expected impact from biosimilars on sales of our established medicines,” Roche said in a 

. Sales for the first 3 months of 2021 were $16.26 billion, down from $16.49 billion in the comparable year-ago quarter.

Roche produces the blockbuster biologic originator products rituxmab (Rituxan), bevacizumab (Avastin), and trastuzumab (Herceptin). These are now facing significant biosimilar competition, “especially in the United States,” the company reported. 

Whereas in the first quarter of 2020 Rituxan, Avastin, and Herceptin accounted for 33% of the pharma sales mix at Roche, that percentage dropped to 22% in the first quarter of this year, the company reported. 

 were down 40% in the just-ended quarter vs the year-ago period. Among hematology products, which include Rituxan, sales were down 37%. Herceptin is sold among a basket of Roche products for treatment of human epidermal growth factor receptor 2–positive cancer, and this portfolio saw an 11% sales decline.

Conversely, sales of new products represented 50% of the total revenue mix, as opposed to 37% this time last year. Products identified as new included pertuzumab (Perjeta), trastuzumab emtansine (Kadcycla), introduced in 2012 and 2013, respectively; atezolizumab (Teqcentriq) and ocrelizumab (Ocrevus), introduced in 2016 and 2017, respectively; and satralizumab (Enspryng) and subcutaneous pertuzumab/trastuzumab (Phesgo), introduced in 2020, among many others.

The pandemic continues to have a downward effect on patient volume at hospitals and health practices, where infusions have declined, Roche said. However, the Switzerland-based pharmaceutical giant has benefited from the sale of medicines used to treat COVID-19. 

For a while now, Roche has battled the effects of biosimilar competition. In its 2020 year-end report, the company predicted that losses to biosimilars that year would be the worst and that the hemorrhaging would start to lessen. Full-year 2020 revenue declines from biosimilars amounted to $6.34 billion. “I think we’ve seen the worst that it can get,” said Bill Anderson, CEO of Roche Pharmaceuticals, 

. At that time, Anderson predicted a negative $5.1 billion biosimilar sales impact in 2021.

Roche has begun another year of biosimilar sales erosion, although the company has said this year will not be as bad as 2020. 

Roche Sees Rejuvenation Amid Sales Declines From Biosimilars, COVID-19

Editor's note: This is part 1 of a series on biologics patents and biosimilars.

The biosimilars pathway in the Biologics Price Competition and Innovation Act (BPCIA) was created to address the needs of biosimilar applicants and speed their products to market for the benefit of patients, but is the pathway working?

Panelists at the Festival of Biologics USA meeting said some tinkering may be necessary to optimize the patent resolution process (aka patent dance) in the BPCIA, particularly when it comes to understanding processes and intellectual property related to manufacturing.

The BPCIA was created in 2010 by legislative fiat, but “whether it’s working or not depends on what expectations you have of the system and how you expected it to work over time,” said Hans Sauer, vice president for Intellectual Property at the Biotechnology Innovation Organization. “The BPCIA as it’s currently interpreted and implemented is perhaps not quite what I and others expected when it was first passed.”

Compared with the 1984 Hatch-Waxman Act for simple molecule chemical compounds (generics), there are more moving parts to the BPCIA. During the patent dance, biosimilar developers and originator companies come to the fence to decide where potential intellectual property infringements may occur and attempt to resolve those issues prior to the biosimilar being launched. It’s one of the vital organs of the BPCIA.

“The patent dance is working for people who chose to use it, right? And it’s not working if litigants make different choices. Does that mean it’s a train wreck? I don’t know,” Sauer said. “I think we see a greater diversity of corporate behavior, of litigation behavior, than certainly what we see in the small molecule space. If you have an expectation that this is supposed to work like the Hatch-Waxman system for small molecules, it does not. It’s certainly working for litigants who have come out on top and who end up getting out of the system what they want, but for the other guys, it’s usually not working.”

The beauty of the patent dance is its flexibility, said Timothy “Tim” J. Shea Jr, biotechnology intellectual property expert and director of Sterne Kessler Golstein and Fox of Washington, DC. “It’s not a one-size-fits-all, as maybe we are more likely to see under Hatch Waxman, and so we see a lot of different strategies in terms of the patent dance and other aspects of the statute.” The BPCIA allows biosimilar applicants to choose the order of battles that are most important to them. “If there are certain patents that are going to drive the decision of whether to launch or when to launch, being able to focus on those early on, I think, is very positive,” he said.

But would more information on manufacturing patents and processes, disclosed earlier, help biosimilar applicants get more products to market faster and with less trouble? Legislation has been drafted to prompt more disclosure from reference product manufacturers to improve clarity and, ultimately, to make the marketplace more competitive. And in December 2020, the Biological Product Patent Transparency Act was signed into law, requiring originator product companies to promptly share relevant patent information with the FDA. Starting in June 2021, this disclosed information would automatically be entered in the Purple Book reference guide for the biologics industry.

However, the risk is that manufacturers burdened with greater disclosure requirements would be fearful of sharing manufacturing secrets and become less willing to innovate, panelists said. “These innovations are extremely valuable, not just to the biosimilar applicant but to the whole industry, and we want to encourage that,” Shea said. “I don’t like the idea of a kind of a draconian provision that just says all this must be disclosed.”

It’s also possible that disclosure requirements could make the process more confusing for the originator product companies, besides too revealing, Sauer said. “If I sit on a portfolio of alternative resins for chromatography columns, columns for purification, or alternative cell culture media that could be used, or others, which do I disclose? The ones that I use may not be the ones the biosimilar company ends up using."

Legislation has raised the specter that companies that fail to sufficiently disclose the patents they hold may lose the right to enforce those patents in the event of infringement. “List it or lose it propositions that we’ve seen throughout these bills have been our greatest concern,” Sauer said. Another reason originator manufacturers may be leery of disclosure laws is that the intellectual property may pertain to multiple products the company produces. Revealing information about one product may compromise another.

One way to enhance the information exchange might be to start the patent discussion earlier in the application process, even several years before anticipated approval and launch of a biosimilar, said Bruce Leicher, moderator of the panel and a strategic law advisor and adjunct processor in Biotechnology Law at the University of New Hampshire Franklin Pierce School of Law.

For that to work, the timing has to be right, said panelist David Korn, vice president of Intellectual Property and Law with PhRMA, a pharmaceutical industry trade association. “Is it that, at some point, it becomes too early to actually engage the full process and the back and forth, and if there are any changes after that, then it would seem like the whole thing needs to be restarted in order to get a true picture of the patents that are relevant to that particular biosimilar.”

Shea agreed that the timing should be worked out so that discussions over intellectual property occur when it’s relevant to have them. “I think you do want to be at a point where the process is fixed enough that it just really makes sense, otherwise it opens up all sorts of cans of worms in terms of being premature.” But an earlier discussion of relevant patents has the potential to “reduce the surprise element for the biosimilar applicant,” he said.

Ultimately, biosimilar developers ought to have a good sense of what information is needed to understand where infringements may lie, Sauer said. After all, they have developed their own manufacturing processes by the time they apply to the FDA for approval. “To my mind, the biosimilar developer is best positioned to know what to look for in the published patent literature and published application literature,” he said. 

“Why is it that we so persistently hear concern about the uncertainty that’s being caused by manufacturing patents?" he asked. "Is it that manufacturers keep getting new patents to improve manufacturing technology that pop out of the system when it’s too late? Is it that biosimilars are genuinely locked into a limited range of technologies, and they discover that all of this ends up being patented by someone?”

More disclosures, earlier in the biosimilar application process, might lead to more competition in biologics, but panelists said this could go too far.