Tony Hagen is senior managing editor for The Center for Biosimilars

Tony Hagen

In a keynote speech to a generic and biosimilar drug industry group, Alex M. Azar, secretary of HHS, gave a pat on the back to outgoing President Donald Trump, praising his policies and executive orders aimed at reducing prescription drug costs.

In addition, accelerated approvals of biosimilars and generic drugs combined with growing market competition since 2017 have contributed to a plateau in drug price inflation the past several years, Azar said at the Association for Accessible Medicine (AAM) GRx+Biosims virtual conference.

He attributed this trend not to pricing restraint on the part of manufacturers but, specifically, to market dynamics and drug policies promoted by Trump.

“Since we released the president’s drug pricing ‘

’ in May 2018, the official government measurement of drug price inflation has been flat. That measure saw the largest drop in nearly 50 years from June 2018 to June 2019. Now, I don’t think that’s because of the goodness of drug companies’ hearts. In fact, I worked at a drug company myself, and I can more or less assure you it’s not. In significant part, it’s because of the market discipline that your companies provide,” Azar said.

study published earlier this year indicate list prices for prescription drugs climbed sharply from the start of the Trump administration through 2018, but net drug prices increased much more moderately during those years, according to the study. The study did not describe drug price behavior after 2018.

“I believe we’ve seen more efforts to promote competition in prescription drug markets from HHS and our colleagues at FDA than we’ve seen since the passage of Hatch-Waxman in the 1980s,” Azar said. The Hatch-Waxman Act (1984) encouraged the manufacture of generic drugs and created a regulatory system for these agents.

“We’ve set records for approvals of generic drugs in 2017 [937], 2018 [971], and 2019 [1171], while also accelerating approvals of biosimilars. The savings that these drugs deliver are massive,” Azar said. There were 10 biosimilar approvals in 2019, a record number, but just 2 so far in 2020.

There are roughly 90 ongoing biosimilar development projects on file with the FDA, which has not officially given any explanation for the reduced number of approvals this year, although in general remarks FDA officials have stated that efforts to approve trials and review treatments related to coronavirus disease 2019 have required a massive shift of priorities and resources.

Generic drug savings totaled $313 billion in 2019, $96.1 billion of that for the Medicare program and $48.5 billion under Medicaid, Azar said, quoting from a 2020 

. “We’ve also taken steps to drive not just faster generic and biosimilar approvals but also faster adoption of these options, and we’ve allowed Part D plans to accelerate substitutions of generic drugs for brand drugs, and we’ve given Medicare Advantage plans new tools to negotiate lower prices that they’ve already used to substitute lower cost biosimilars.”

Azar said a 2018 HHS report identified $3 billion in potential savings on $9 billion that Medicare Part D plans are spending annually on name brand drugs that have generic alternatives. Achieving those savings involves eliminating “kickbacks” to middlemen in the drug supply chain and fixing the “broken rebate system” that rewards payers and pharmacy benefit managers for preferring certain drugs, whether or not they are lowest cost, he said.

“We’re also working to propose rules around Part B drugs that have the potential to be equally significant for American drug costs, especially with regard to rapidly rising expenditures on biologics, which today represent almost 40% of prescription drug spending,” Azar said.

He said biosimilar uptake in the health care marketplace has been “slower than we’d like, in part because the Part B system actually encourages prescribing more expensive options. If we can bring to the biologics market just a fraction of the savings that generic drugs have brought to American patients, that will be a transformative shift.”

Hernandez I, San-Juan-Rodriguez A, Good CB, et al. Changes in list prices, net prices, and discounts for branded drugs in the US, 2007-2018. 

. 2020;323(9):854-862. doi:10.1001/jama.2020.1012

Articles

HHS Secretary Alex M. Azar said efforts and policies to counter a sharply upward drug price trend have been successful, in a talk with the Association for Accessible Medicine.

Azar Says Trump's Drug Price Shake-up Is Working

The survival of the Affordable Care Act (ACA) without the individual mandate seemed a distinct possibility following oral arguments in the Supreme Court, and this bodes well for the survival of the Biologics Price Competition and Innovation Act (BPCIA), which is part of the ACA statute and enacts the pathway for biosimilar approvals.

“It’s hard for you to argue that Congress intended the entire Act to fall if the mandate was struck down,” Chief Justice John Roberts 

. The individual mandate dictated that individuals must have health insurance or pay a penalty for not having it, although the penalty was abolished in 2019. The argument before the court is whether the ACA and its provisions can be salvaged without the mandate or if they must be struck down in their entirety. 

Roberts said “there seems to be compelling evidence” that the intent of Congress was for the “rest of the law to survive if an unconstitutional provision were severed.”

The potential loss of the BPCIA was cause for concern in the biosimilars community, where the pathway has enabled 18 biosimilars to come to market so far, making lower-priced versions of costly biologics available to many patients and thereby expanding access to treatment. It is believed that a chaotic interruption to the development of the biosimilars market could 

 without the BPCIA and until Congress develops patch-up legislation as a replacement.

For more about the Supreme Court hearing, visit 

The survival of the biosimilars approval pathway seemed on surer footing today following oral arguments at the Supreme Court over the Affordable Care Act and the severability of its provisions.

Supreme Court Hints Biosimilar Route Might Be Preserved

Samsung Bioepis said it has initiated a phase 1 clinical trial for its denosumab biosimilar candidate (SB16) for osteoporosis.

The proposed biosimilar references Amgen’s blockbuster Prolia, which in the third quarter of 2020 garnered $701 million in revenues, up 11% from the comparable year-ago quarter.

Prolia was first approved for osteoporosis with high risk of fracture in 2010 and has been approved for multiple indications since, including bone loss in patients with prostate or breast cancer undergoing hormone ablation therapy, bone loss for men with osteoporosis and high fracture risk, and glucocorticoid-induced osteoporosis.

Samsung Bioepis, based in Incheon, Republic of Korea, said the 

is a randomized, double-blind, 3-arm, single-dose study to compare the pharmacokinetics, pharmacodynamics, safety, tolerability, and immunogenicity between SB16 and reference denosumab in a target population of 168 healthy male participants.

The 3 study arms will involve dosing with SB16 or either the EU or US versions of the reference product.

The company is targeting the lucrative osteoporosis market dominated by Prolia, an Amgen product.

Samsung Launches Clinical Study of Denosumab Candidate

Highlighting challenges and ongoing efforts, Sarah Yim, MD, director of the Office of Therapeutic Biologics and Biosimilars (OTBB) delivered a progress report on the FDA’s Biosimilars Action Plan (BAP) at the Association for Accessible Medicine (AAM) GRx+Biosims annual conference.

The BAP was created in 2018 to support biosimilar development by improving efficiency of the development and approval process; improving scientific and regulatory guidance; improving education about biosimilars for patients, clinicians, and payers; and improving the competitive environment by “reducing gaming of FDA requirements or other attempts to unfairly delay competition,” Yim said.

The FDA continues work to develop indices of critical quality attributes for biosimilars, identify pharmacodynamic (PD) biomarkers, and investigate in silico modeling, in which computers are used to model pharmacologic or physiologic processes. Each of these qualifies as a potential development tool, “but because of resource limitations related to [coronavirus disease 2019], we are not yet ready to release the first batch of biosimilar product recommendations. Hopefully, we’re close,” Yim said.

 to help biologics developers and other stakeholders to understand at what point the exclusivity protection clock begins to tick for a reference product. The guidance was also intended to help innovator companies know what information to provide the FDA to help the agency decide when product exclusivity begins. Six years later, that guidance is still in draft form, although progress continues, Yim said. “We’re still working on biologic product regulatory modernization and finalizing guidance on reference product exclusivity and post-approval manufacturing.”​ 

The FDA would like to make various improvements to improve biosimilar development, and these include optimizing review staff time, exploring PD markers and assays that can help ascertain biosimilarity between biosimilar candidates and reference products, providing product specific guidance, and partnering with international regulatory authorities to reduce redundant activities. “To take product development and review to the next level in efficiency, more will need to be done,” Yim said.

“We’ll need to improve the status of biosimilar-related knowledge management and expand its scope to ensure not only consistency but provide space for ideas regarding improvements in best practices to be easily known and shared,” she said.

Another area of focus that could lead to important gains for biosimilars is patient education and reduction of anticompetitive messaging, she said. This can be achieved, in part, “by figuring out how to best exploit the educational gold mine of information that’s already available from real world experience with biosimilars. More than a decade of experience is available for some biosimilars in Europe, and at least several years of information should be available for some of the US-approved biosimilars.”

Yim noted the FDA’s achievement in modernizing the Purple Book, which originally was a bare bones listing of FDA-licensed biological products and now is an expanded, searchable, online database.

Also, in 2019, the FDA published guidance on biosimilar interchangeability with reference products and on the design and evaluation of comparative analytical studies for determining biosimilarity.

“We’ve made significant strides in advancing educational resources and activities and have recently begun a 2-year curriculum development project,” Yim said. “We also plan to begin work this year on developing additional, wide-reach education forums.”

Yim also said the FDA and the Federal Trade Commission have made “significant progress” combating anticompetitive behaviors by innovator companies and others that seek to oppose the advancement of biosimilars.

“Moving forward, we will be looking toward identifying and expanding high value activities that could help take biosimilar and interchangeable product access to the next level in the 2020s,” she said.

Sarah Yim, MD, director of the Office of Therapeutic Biologics and Biosimilars (OTBB), highlighted the ways the FDA is working to remove blocks and wedges hindering biosimilars.  

OTBB Director Discusses FDA's Roadmap for Biosimilars

Investigators have presented evidence of what they say are successful, first-time tests of a multibiomarker disease activity (MBDA) score in patients with rheumatoid arthritis (RA). Separate comparative studies of infliximab and adalimumab biosimilars vs their reference counterparts were presented at the American College of Rheumatology (ACR) Convergence 2020 meeting.

The value of the MBDA score (Vectra) is that it consists of measures of 12 serum proteins and is highly sensitive, thereby offering an alternative to “subjective” clinical observation of patient progress, they explained.

“Comparison of MBDA scores between treatment groups may provide additional evidence of biosimilarity using an objective, quantitative assessment of disease activity that is independent of the potential subjectivity of joint counts or patient or physician global assessments,” said Jonathan Kay, MD, of the University of Massachusetts Medical School, who served as lead investigator for both studies.

Both studies involved Pfizer biosimilars and were sponsored by Pfizer.

In the first study, patients were randomized to treatment with an infliximab biosimilar (Ixifi) vs reference infliximab (Remicade) sourced from the European Union.

Investigators enrolled 650 patients who met 2010 ACR/EULAR disease classification criteria and had ≥ 4 months of RA duration. They received 3 mg/kg of infliximab intravenously at weeks 0, 2, 6 and then every 8 weeks, in combination with methotrexate (MTX). MBDA scores were on a scale of 1 to 100, with 100 being the highest level of disease activity. They reported initial treatment period activity for weeks 0 to 30.

Baseline mean scores for patients receiving the infliximab biosimilar were 61.3 vs 58.8 for the reference product. For the overall population, the mean scores at 30 weeks were 46.9 for both biosimilar and reference groups.

The proportions of patients with high MBDA scores at baseline in both the biosimilar and reference cohorts were similar: 66.0% vs 66.9%, respectively. At week 30, the proportions of patients with high MBDA scores decreased to 42.3% and 40.2%, respectively.

Investigators said the decreases in individual serum biomarker levels that formed the composite MBDA score also were similar between biosimilar and reference groups. They identified 3 biomarkers for which this was true—serum amyloid A, tumor necrosis factor receptor 1, and VEGF-A—but they said it held true also for other biomarkers included in the MBDA score.

Mean MBDA scores decreased 15.2 and 14.1 points, respectively from baseline to week 6 in the 2 groups, and disease stability between cohorts was noted through week 30.

In the second study, investigators enrolled 597 patients with RA by 2010/EULAR criteria and disease duration of ≥ 4 months. They were randomized to adalimumab biosimilar (Abrilada) or European Union–sourced adalimumab reference product and received 40 mg subcutaneously every other week, in combination with MTX.

Mean MBDA scores were calculated at baseline and weeks 6, 12, and 26. At baseline, the mean MBDA scores for the biosimilar and reference groups were 57.2 and 58.3, respectively. “Mean values of MBDA scores were comparable between treatment groups at all measured time points through 26 weeks,” the investigators wrote.

The proportions of patients with high MBDA scores decreased to 45.5% and 41.7% at week 26. Mean MBDA scores dropped from baseline by 11.9 and 12.4 points, respectively, by week 6; by 11.7 and 12.4 points at week 12; and by 14.3 and 15.5 points at week 26, respectively. Again, individual serum biomarker levels tracked one another closely between biosimilar and reference cohorts.

The mean scores over the 26 weeks for both cohorts were similar, leading adalimumab investigators to conclude: “MBDA score based on 12 serum biomarkers provides a sensitive and objective clinical assessment of biosimilarity that does not require physical examination of the patient or subjective patient global assessment of DA."

1. Kay J, alvarez D, Rehman MI, Zhang M, Iikuni N. Use of multi-biomarker disease activity scores to assess biosimilarity in a phase 3, randomized controlled trial comparing biosimilar infliximab-qbtx (PF-06438179/GP1111) with EU-sourced reference infliximab in patients with active RA. Presented at: ACR Convergence 2020; November 5-9, 2020. Abstract 1204.

2. Kay J, Bock A, Iikuni N, Zhang W, Alvarez D. Use of multi-biomarker disease activity scores to compare biosimilar adalimumab-afzb (PF-06410293) with EU-sourced reference adalimumab in a phase 3, randomized, double-blind trial in patients with active RA. Presented at: ACR Convergence 2020; November 5-9, 2020. Abstract 1233.

A multibiomarker disease activity score looks at serum protein activity for a more sensitive evaluation of biosimilarity, investigators said at the American College of Rheumatology Convergence 2020 meeting.

Multibiomarker Test Reads Out Positive in 2 Pfizer-Sponsored Studies

Biosimilar company Biocon Biologics said it will 

 a $150 million investment from Goldman Sachs.

Biocon said in a statement that it regarded the capital infusion as a sign of confidence from the global investment community in the potential of the Bangalore, India-based company.

“This capital injection by Goldman Sachs will enable us to make prudent investments in [research and development], high-quality manufacturing, as well as establish a global commercial footprint,” said Christiane Hamacher, PhD, CEO of Biocon Biologics.

Biocon markets 2 biosimilars in the US: a trastuzumab (Ogivri) and a pegfilgrastim (Fulphila), both in partnership with Mylan. The companies have also launched an insulin glargine (Semglee), which references Lantus. 

The product is essentially a biosimilar, but was not approved as one owing to the regulatory pathway followed. Biocon and Mylan are seeking biosimilar and interchangeable status for Semglee. Interchangeable status would mean pharmacists could dispense it without physician involvement. 

Biocon Biologics nets a $150 million investment from Goldman Sachs to further its development and marketing of biosimilars. 

Goldman Sachs Bets Large on Biocon Biosimilars

Biosimilar developments reported at the American College of Rheumatology (ACR) Convergence 2020 virtual meeting included data from safety and efficacy trials for Pfizer and Celltrion versions of adalimumab.

Positive safety, immunogenicity and efficacy findings were reported for the Pfizer adalimumab biosimilar PF-06410293 (Abrilada, ADL-PF) in a study of patients with moderate-to-severe active rheumatoid arthritis (RA).

In an earlier study, ADL-PF, which has been approved in the United States and European Union, was compared with reference adalimumab sourced from the European Union (ADL-EU) and demonstrated therapeutic equivalence in patients with active RA. Comparable safety, efficacy, and immunogenicity was maintained up to week 56, and no differences in outcomes were observed for patients who underwent a blinded switch to ADL-PF at week 26.

At the ACR Convergence 2020, updated findings were presented for weeks 52 to 92 in patients who continued ADL-PF (N = 552). At week 52, all patients remaining on ADL-EU were switched to ADL-PF. Investigators said efficacy response rates at week 78 were 84.2% for all patients, and 83.4%, 85.8%, and 84.3% for the biosimilar, week 26 switch, and week 52 switch groups, respectively.

Investigators said response rates according to the ACR20 scale, which defines positive change as a 20% improvement in a core set of measures, were comparable across the 3 groups.

On safety, investigators said ADL-PF was generally well tolerated across groups with comparable safety profiles. With regard to immunogenicity, investigators reported comparable rates of antidrug antibodies (ADAs) and neutralizing ADAs.

In a separate study presented at ACR Convergence 2020, investigators demonstrated efficacy and safety equivalence of the adalimumab biosimilar candidate CT-P17 to reference adalimumab in patients with moderate-to-severe active RA.

CT-P17 is a high concentration (100 mg/mL), citrate-free formulation of the reference product. Investigators sought to show equivalence by efficacy at week 24 and by pharmacokinetics and overall safety over the first 24 weeks of administration.

Investigators randomized 648 patients 1:1 to reference and biosimilar adalimumab. They found that the ACR20 response rate at week 24 was 82.72% in both groups. Confidence intervals for treatment difference were fully within parameters set by the European Medicines Agency and the FDA. Secondary efficacy end points also were similar between cohorts.

Investigators noted a slightly higher serum trough concentration in patients receiving CT-P17 vs reference adalimumab at week 24: 5.3 μg/mL vs 4.3 μg/mL (

Safety profiles between groups also were similar. Most events were grade 1/2. Among the CT-P17 cohort (n = 324), there were 5 treatment-emergent adverse events leading to study discontinuation, vs 8 for the reference group (n = 324). Events leading to discontinuation considered related to the adalimumab treatment were 2 vs 4, respectively.

The number of patients who developed ADAs was lower at week 24 for those on CT-P17 vs reference (32.3% vs 35.8%, respectively). Among patients receiving CT-P17, 83 (25.6%) had neutralizing ADAs, vs 103 (31.8%) receiving reference product.

In March 2020, Celltrion applied for CT-P17 marketing authorization in the United States and Europe. Those applications are still pending.

1. Fleischmann R, Alvarez D, Bock A, et al. A randomized, double-blind phase 3 study comparing the efficacy, safety and immunogenicity of PF-06410293 (Abrilada™), an adalimumab (ADL) biosimilar, and reference ADL (Humira®) in patients with moderate to severe active RA: results from weeks 52-92. Presented at ACR Convergence 2020; November 5-9, 2020. Abstract 0798.

2. Kay J, Jaworski J, Wojciechowski R, et al. A randomized, double-blind, phase 3 study to compare the efficacy and safety of a proposed high concentration (100 mg/mL) adalimumab biosimilar (CT-P17) with reference adalimumab in patients with moderate-to-severe active rheumatoid arthritis. Presented at ACR Convergence 2020; November 5-9, 2020. Abstract 0800.

Poster presentations at the American College of Rheumatology (ACR) Convergence 2020 meeting shed light on performance of adalimumab versions. 

ACR Abstract Roundup: Pfizer and Celltrion Agents Demonstrate Safety, Efficacy

A study of Celltrion’s CT-P17 adalimumab biosimilar candidate demonstrated 

 and safety equivalence to US and EU samples of reference adalimumab

; and a separate study of difference administration methods for CT-P17 demonstrated equivalent outcomes

, in findings presented at American College of Rheumatology (ACR) Convergence 2020, the ACR’s virtual annual meeting.

Adalimumab reference product is indicated for arthritis, plaque psoriasis, ankylosing spondylitis, Crohn disease, and ulcerative colitis. CT-P17 was developed as a high concentration (100 mg/mL) citrate-free formulation of the reference product.

PK and safety of CT-P17 relative to US- and EU-marketed reference adalimumab were evaluated in a healthy population (N = 312) randomized to a single dose in each of the 3 arms.

Investigators said the 90% CI intervals for each of the PK parameters were within the predefined equivalence margin of 80% to 125%; and secondary PK parameters were similar among the 3 treatment groups. Mean serum concentrations up to day 71 were comparable among the trial cohorts, they said.

Investigators also described a comparable safety profile among the 3 cohorts. Most treatment-emergent adverse events (TEAEs) were grade 1/2. The most frequent of these was injection site reaction, but no clinically notable differences were observed in lab results, vital signs, electrocardiogram results, or physical examinations among the patient groups.

With regard to immunogenicity, patients testing positive for antidrug antibodies (ADAs) and neutralizing ADAs were comparable in each cohort. In addition, each group followed a similar curve as numbers of patients testing positive increased over the study term.

Investigators concluded that PK equivalence of CT-P17 relative to high concentration (100 mg/mL), citrate-free formulations of the US- and EU-samples of reference product was demonstrated. Safety was also comparable, they said.

In a separate, phase 1 randomized, single-dose study in healthy participants comparing PK and safety of CT-P17 auto-injector (AI) and prefilled syringe (PFS) products, investigators observed comparable findings for mean peak and total drug exposure as well as for secondary PK parameters, safety, and immunogenicity.

The trial randomized enrollees 1:1 to 40 mg of CT-P17 AI (n = 98) or PFS (n = 95). Investigators said 92 patients completed treatment on AI and 83 completed treatment with PFS.

In both groups, mean peak and total systemic exposure were equivalent because the 90% CIs were within the predefined equivalence margin of 80% to 125%, investigators said. Maximum dose duration (Tmax) occurred at 132 hours for both treatment groups. Secondary PK parameters also were comparable between the AI and PFS groups, as were mean serum concentrations.

On safety, 60.2% and 51.7% of patients reported ≥ 1 TEAE in the AI and PFS groups, respectively. There were 2 TEAEs (grade 3), and all other TEAEs were grade 1/2. TEAEs considered related to CT-P17 were reported by 47 (50.5%) and 38 (43.7%) of patients in the AI and PFS groups, respectively. The most frequent were headache (11.8% and 9.2%) injection site reactions (8.6% and 6.9%).

1. Pharmacokinetics and safety of CT-P17, a proposed high concentration (100 mg/mL) adalimumab biosimilar, in comparison with EU-approved adalimumab and US-licensed adalimumab; results of a phase 1, randomized, double-blind, three-arm, single-dose study in healthy subjects. Yu KS, Jang I, Lim HS, et al. Presented at ACR Convergence 2020; November 5-9, 2020. Abstract 0204.

2. A phase 1, randomized, open-label, parallel group, single-dose study to compare the pharmacokinetics and safety of the auto-injector and pre-filled syringe of CT-P17, a proposed, higher concentration biosimilar (100 mg/mL) adalimumab, in healthy subjects. Keystone EC, Furst D, Kay J, et al. Presented at ACR Convergence 2020; November 5-9, 2020. Abstract 0199.

Separate studies including one on application methods for CT-P17 were reported at the American College of Rheumatology Convergence 2020 meeting.

Celltrion's CT-P17 Adalimumab Biosimilar Candidate Demonstrates Equivalence

The European Union is often held up as an example of biosimilar success relative to the United States, but in a new 

, Medicines for Europe describes an intellectual property briar patch into which competitor generic and biosimilar companies dare not get thrown for fear of endless entanglements.

The pharmaceutical industry has a “social contract” to bring affordable and life-saving medicines to market, but increasingly, exploitation of the legal framework for supporting patent rights is undermining this contract, change proponents said in a virtual conference timed with the release of the paper.

“This reduction in adherence to that social contract is getting worse. The tactics are being employed in a more sophisticated manner—more vigorously than ever before,” said James Burt, executive vice president of Europe, Middle East, and North Africa for Accord Healthcare.

In the United States, industry observers often describe “patent thickets” thrown up by originator drug companies to protect their products from competition. These multiple patents make it difficult for biosimilar and generic companies to weed out the patents that count from the ones that don’t, and addressing each patent involves a commitment of time and money that may delay a lower-cost competitor product from reaching market.

In Europe, patent thickets also exist and are made worse by regulatory and legal standards that enable the spawning of “divisional patents” that are filed after the original patents and effectively subdivide the intellectual property, leading to costly and time-consuming courtroom debates over patent validity, authors of the paper wrote.

These divisional patents are filed in “cascades” to take advantage of laws that keep competitor products off the market until disputes over intellectual property are resolved. In actuality, those resolutions may never happen, said Corinna Sundermann, head of Intellectual Property in the Pharma Division at Fresenius Kabi, a Bad Homburg, Germany-based biosimilar developer.

“Legal certainty” is the standard for whether a competitor product is likely to infringe an originator company’s product, and “We do not reach legal certainty because there is always a divisional pending,” Sundermann said. “The problem here is that the European Patent Office allows an unlimited number of divisionals.”

In some cases an original or “parent” patent of dubious merit that seems likely to fail a court examination will be withdrawn by the innovator company “before its revocation,” but divisional patenting on that same product may continue, “and this changes the situation completely,” Sundermann said.

The theory is that divisionals are supported by new findings that might not have been appropriately defined and protected by the original patent; however, the late-term discovery of information supporting a divisional application does tend to arouse suspicion, Sundermann said. “No one can tell me," she added, "that 7 years after the launch of a product a patentee finds out that there is new experimental data” that is worthy of enhancing exclusivity protections for a given product.

Divisional patent filings have become a significant problem in Europe recently, she said. Another problem faced by generic and biosimilar companies is “patent linkage,” which prevents biosimilars and generics from entering market until patent status for an originator product is resolved; therefore, a mere claim of infringement by an innovator company can interfere with marketing authorization (MA) for a competitor product. Patent linkage is prohibited under European law but forms of it still exist, according to the white paper.

“Despite this system of mandatory arbitration having come to an end, an application for an MA continues to be considered to be grounds for patent infringement proceedings in Portugal,” authors of the paper wrote. Slovakia and Hungary also were singled out as countries where this occurs.

As in the United States, product hopping, or abrupt switches to somewhat different drug versions by innovator companies, is a problem in Europe, the paper explained. Hopping by originator companies discourages use of the former products, competitor generics, and biosimilars, because the newer product is assumed to be superior.

Anticompetitive rebates, which undercut the lower prices of biosimilars and generics and interfere with payers’ formulary decisions, are rife in Europe, too, the authors wrote. Product “denigration,” or misleading statements about competitor products, also was the focus of several pages of discussion in the report.

All of these issues make competitor companies very reluctant to enter the market, and this has dire implications both for patients and the health of the pharmaceutical sector, speakers said. “We have to address the sustainability problem of the off-patent sector [generics and biosimilars], otherwise we won’t have one. It’s going to shrink,” Burt said.

“Whatever the innovators do to hold off competition will be far more lucrative than any recourse they might be made to bear if they’ve overstepped,” he added. “This is one of those situations where heads the brand industry wins, tales the generic industry loses.”

Vidal R, Drew C, Lavin B, Ellis B, Bruce E; Legal Affairs Committee of Medicines for Europe. Anatomy of a failure to launch: a review of barriers to generic and biosimilar market entry and the use of competition law as a remedy. Medicines for Europe. Published November 5, 2020. 

https://medicinesforeurope.com/docs/2020.11.04-Medicines-for-Europe-Whitepaper.pdf

Medicines for Europe, a generic and biosimilar trade association, contends in a white paper that legal and regulatory loopholes increasingly keep competing drugs off the market. 

Medicines for Europe Takes Aim at Barriers to Entry for Biosimilars and Generics 

Israel-based Teva Pharmaceutical Industries 

 revenues of $4 billion for the third quarter of 2020 and said earnings were driven in part by rituximab biosimilar (Truxima), which it launched on the US market in 2019 in partnership with Celltrion Healthcare.

Celltrion developed the product, which became the first rituximab biosimilar 

The company reported combined biosimilar and generic product revenues of $928 million for the third quarter, which is up 2% vs the year-ago quarter. “This increase was mainly due to higher revenues from Truxima and from our ProAir (albuterol inhaler) authorized generic, partially offset by lower volume of other generic products,” a Teva statement 

. Specific product revenues for Truxima, Teva’s first biosimilar offering, were not provided.

Also in conjunction with Celltrion, Teva launched the trastuzumab biosimilar Herzuma in the United States in March 2020. In August, the company announced a 

 with Alvotech to commercialize 5 unnamed biosimilars in the United States.

Launched in the US market in late 2019, Truxima (rituximab) has become a significant revenue driver for Teva.