Tony Hagen is senior managing editor for The Center for Biosimilars

Tony Hagen

Anti—tumor necrosis factor (TNF) biosimilars can provide a more cost-effective, targeted approach to treatment of immune-mediated inflammatory diseases, according to a 

“Along the course of the last 2 decades, TNF inhibitors, particularly etanercept, infliximab and adalimumab, have revolutionized the management of chronic immune-mediated inflammatory diseases; however, their relatively high cost prevented healthcare systems from exploiting their full clinical benefit,” Mourad F. Rezk, MD, global head of Medical Affairs for Biogen's biosimilars portfolio, and Burkhard Pieper, director of Scientific Affairs for Biogen, wrote in 

The wealth of real-world evidence on these agents suggests that not only is use increasing but also these drugs are improving access and outcomes, they explained.

“This includes the opportunity to realize clinical goals such as early initiation of biological treatment, treating to target, continuing treatment to maintain remission or low disease activity and reducing disease burden,” they wrote.

However, optimizing these biosimilars requires that biosimilars be approved “expeditiously,” competition against originator drugs is “optimized,” and patients are switched to biosimilars. “All of these actions will result in maximum cost savings, which can then be reinvested into patient care,” they wrote.

Biogen turned in a good second-quarter 2020 financial performance, with modestly improved earnings; however, biosimilar revenues 

Articles

Two Biogen officials make the case for getting anti–tumor necrosis factor (TNF) biosimilars into wider play.

Biogen: Anti-TNF Biosimilars Are Underutilized

Two China-based companies have reached a tentative 

 to commercialize a bevacizumab biosimilar in the Chinese market assuming approval is granted by the China National Medical Products Administration (NMPA).

Bio-Thera Solutions, based in Guangzhou, and BeiGene, of Beijing, said the licensing agreement is for Bio-Thera’s BAT1706, an investigational biosimilar to the reference product Avastin, which in China is indicated for advanced, metastatic, and relapsed non—small cell lung cancer and metastatic colorectal cancer.

BeiGene would have the rights to develop manufacture and commercialize BAT1706 in China, including Hong Kong, Macau, and Taiwan. Macau is an independently administered territory of China. Taiwan is a self-governed country whose medicinal products are approved by the Taiwan Food and Drug Administration.

The deal calls for Bio-Thera to receive an upfront payment and milestone payments up to a total of $165 million. In addition, Bio-Thera would receive royalties on future sales. Final approval of the marketing deal is subject to shareholder approval.

“This collaboration allows Bio-Thera to leverage BeiGene’s experience and expertise to accelerate the development and commercialization of BAT1706 as a single agent regimen or as a component of combinational therapies, and to help increase patient access to this important cancer therapeutic at affordable prices,” said Shengfeng Li, CEO of Bio-Thera.

BeiGene believes the bevacizumab biosimilar has the potential for wide acceptance in China. “BAT1706…could become an important treatment option for solid tumor indications in China such as colorectal, lung, and liver cancers,” said Xiaobin Wu, PhD, president of BeiGene. "It brings us the opportunity to broaden our portfolio of commercial and registration-stage products in China and is complementary to our in-licensed and internally discovered medicines, such as tislelizumab, our marketed anti—PD-1 antibody that has also been filed in China for lung and liver cancer indications."

The NMPA accepted the biologics license application for BAT1706 in June 2020. Bio-Thera plans to file for BAT1706 marketing approval in the United States and Europe by the end of 2020.

Bio-Thera has 5 drug candidates in late-stage clinical trials, one of which, Qletli, is an adalimumab biosimilar.

BeiGene has more than 4200 employees in China, the United States, Australia, Europe, and other countries. It has 2 “internally discovered” oncology products: zanubrutinib (Brukinsa), a Bruton tyrosine kinase inhibitor that is marketed in the United States and China; and the anti—PD-1 antibody tislelizumab, which is sold in China. The company aims to license and distribute in China other oncology products from Amgen, Celgene Logistics Sàrl, and EUSA Pharma.

 NMPA approval to initiate a phase 1 clinical study to evaluate the pharmacokinetics and safety of BAT2206, a proposed ustekinumab biosimilar referencing Stelara.

From China to Taiwan, BeiGene and Bio-Thera Solutions hope to capture a large share of the bevacizumab biosimilar market.

BeiGene, Bio-Thera Carve Out Bevacizumab Market

Among an increasingly crowded field for aflibercept biosimilar contenders, 2 Germany-based biosimilars companies have launched a phase 3 equivalence study for FYB203, an aflibercept candidate for the treatment of patients with neovascular age-related macular degeneration (nAMD).

The product was developed by Formycon, and in May, the company announced that the first regulatory approvals had been granted for the randomized, double-blind, multicenter trial comparing FYB203 with the reference product, Eylea, on the basis of efficacy, safety, and immunogenicity. Despite the coronavirus disease 2019 (COVID-19) pandemic, the enrollment phase of the trial is on schedule with the plans announced 3 months ago.

Formycon’s partner in this is Bioeq, a company with expertise in product management, clinical development, product administration systems, and licensing. Bioeq is sponsoring the phase III trial. Santo Holding, a Swiss company, holds the rights to global commercialization.

nAMD, also known as wet AMD, is one of the main causes of loss of vision in people over the age of 50 in developed countries. Aflibercept inhibits vascular endothelial growth factor (VEGF), which is the cause of excessive formation of blood vessels in the retina and leads to progressive vision loss.

According to Formycon, Eylea is the top-selling drug in this market. The Regeneron product achieved revenues of $4.64 billion in 2019, up from $4.08 billion in 2018. As patents on Eylea have yet to run their course, there are no aflibercept biosimilars on the market in the United States or Europe. The product first 

According to Regeneron, the US and EU composition-of-matter patents on aflibercept will expire in 2023 and 2025, respectively. US manufacturing, formulation, and administration regimen patents on Eylea expire in 2026, 2027, and 2032, respectively, and formulation patents in the European Union expire in 2027. Regeneron has indicated that it may attempt to extend product exclusivity for Eylea by filing additional product claims. The drug loses its patent protection in China and Japan in 2022.

Aflibercept was approved for wet AMD by the FDA in 2011. It subsequently received additional indications for diabetic macular edema (DME) and diabetic retinopathy in patients with DME. Most recently, the FDA approved Eylea injection for diabetic retinopathy and a prefilled syringe product containing aflibercept. The prefilled syringe product was launched in the United States in December 2019. It was approved by the European Medicines Agency (EMA) in April 2020.

In a statement, Formycon and Bioeq explained that the FYB203 study has been designed in accord with the FDA, EMA, and the Japanese Pharmaceuticals and Medical Devices Agency.

“We are delighted that our second project in the field of ophthalmology is now starting the phase 3 study,” 

, chief operating officer of Formycon, said in a statement. “Given the extensive experience from the FYB201 project and the successful cooperation with Bioeq GmbH, we are confident that we will also be able to develop a high-quality and cost-effective biosimilar with FYB203.”

Other biosimilar developers that are positioning to enter the aflibercept market are Momenta Pharmaceuticals (M710), Altogen (ALT-L9), and Amgen, which began a phase 3 trial for ABP 938 earlier this year. Also, Coherus BioSciences has an aflibercept biosimilar (CHS-2020) in pre-clinical development. Samsung Bioepis also seeks to enter this market with SB15. The company recently 

Multiple contenders are lining up for the pending expiration of patents on the blockbuster Regeneron reference product for wet age-related macular degeneration.

Formycon, Bioeq Enroll First Patient in Phase 3 Aflibercept Study

Celltrion companies have developed biosimilar forms of infliximab for subcutaneous and intravenous use, but now the Incheon, Republic of Korea—based Celltrion Group is developing what would be the world’s first oral infliximab formulation, a tumor necrosis factor–alpha inhibitor, for the treatment of inflammatory bowel disease (IBD).

Celltrion is doing this in collaboration with the United Kingdom—based Intract Pharma, which specializes in oral therapies.

“A technical alliance between Intract Pharma and Celltrion Group allows for the development of oral infliximab that is safe, highly efficacious, and convenient,” Celltrion Group said in a 

Intract will be responsible for development and clinical validation of the product. Celltrion will supply drug material and provide support.

Intract said in a statement that the proposed oral infliximab product has UK approval to proceed to phase 1b/2a clinical trials in patients with IBD. Those trials are expected to commence in the second half of 2021, without a requirement for additional preclinical research or a clinical safety study.

Officials said the oral infliximab is expected to be stable at room temperature, “offering simple distribution, storage, and administration for patients at home.”

Based on this partnership, more oral antibodies could be developed, they added. “Collaboration between the two parties is expected to open new doors for the development of additional orally-delivered antibodies.”

“We anticipate that the oral infliximab product which we will co-develop with Celltrion Group will have an improved safety profile and will offer a less expensive biotherapeutic treatment for IBD. We are hopeful that the product will address a large proportion of the IBD market, potentially replacing steroid and immune-suppressive drugs in addition to capturing a large share of the biologics market,” said Bill Lindsay, CEO of Intract.

Celltrion Group includes Celltrion and Celltrion Healthcare. The 2 companies are interconnected and do research, development, and manufacture of biosimilars and other drugs.

Intract Pharma “has pursued innovation in oral drug delivery as a means to improve on current therapies, making them safer and more effective for patients,” the company said.

Celltrion's infliximab (Rensima) is also being 

 in the CATALYST trial as a possible inflammation control for patients with coronavirus disease 2019.

Intract Pharma believes infliximab can be delivered orally and, in conjunction with Celltrion Group, aims to apply its technology and expertise to make it happen.

Celltrion, Intract Pharma Strive for World's First Oral Infliximab

In what a company spokesman described as a minor setback, Coherus BioSciences has seen its Udenyca pegfilgrastim biosimilar 

 from the 2021 national preferred formulary list for the pharmacy benefit manager (PBM) Express Scripts, whose revenues in 2017, prior to its takeover by Cigna, amounted to over $100 billion.

Amgen’s Neulasta originator pegfilgrastim product was also switched to nonpreferred status on the 2021 formulary.

“Less than 5% of the pegfilgrastim market by unit volume is reimbursed through the nonmedical/pharmacy benefit,” the Coherus BioSciences spokesman said. “Express Scripts represents only a fraction of the pharmacy benefit, so a fraction of the ~5% volume.” The spokesman said the company is mainly focused on moving Udenyca through the medical benefit side, which applies to hospital and clinic administration of the drug.

Formulary placements with PBMs typically involve negotiations with manufacturers over rebates and discounts with manufacturers. Two other pegfilgrastim biosmilars, Sandoz’ Ziextenzo, and Biocon’s Fulphila, remain on the Express Scripts preferred list for 2021. All 4 pegfilgrastims, including the reference product, were included on the 2020 preferred list.

There was no inclusion on the list or reference to Pfizer’s Nyvepria pegfilgrastim biosimilar, which got an FDA approval in June and is expected to be launched in 2020.

Pegfilgrastim is used for the treatment of infection associated with febrile neutropenia in patients undergoing treatment with myelosuppressive anticancer agents. The drug is a granulocyte colony stimulating factor.

Despite the formulary placement outcome, Coherus BioSciences has glowing expectations for Udenyca, which was launched on the US market in January 2019.

In a 2020 second quarter earnings call on June 30, Denny M. Lanfear, president and CEO, 

 the market for Udenyca was expected to grow throughout the remainder of 2020, supported by a rebound in treatment of patients with cancer following the coronavirus disease 2019 (COVID-19)—induced slump. Further, updated National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines have contributed to a rise in use of pegfilgrastim.

Express Scripts is aggressive about price negotiations in order to offer attractive health care options for the employers, managed care providers, health insurers, and others it represents. The company has extended that focus to lobbying Congress to tamp down specialty drug costs. Although the proportion of patients who use them is relatively small, biologics alone represent 42% of the total medicines market.

Express Scripts has urged Congress to eliminate manufacturers’ ability to set prices for certain critical drugs under Medicare Part D (prescription drugs) and has urged that Part D-style negotiation be introduced for Part B drugs (infused drugs). Further, the PBM has urged that coverage of some Part B drugs be shifted to Part D.

As of press time, Amgen had not responded to a request for comment. Second quarter 2020 sales for 

 dropped 40% to $609 million vs $1 billion in the comparable year-ago quarter, largely due to growing biosimilar competition.

Express Scripts, the country's largest pharmacy benefit manager, has reshuffled its preferred formulary list for 2021, giving preference to fewer pegfilgrastim products than in 2020.

Amgen, Coherus Pegfilgrastims Lose Formulary Placement

Is the FDA a little overworked during the coronavirus disease 2019 (COVID-19) pandemic? Consider that over 270 clinical trials specifically related to COVID-19 had been launched by July 31, 2020, and more than 570 additional clinical trials are in planning stages.

But according to Anand Shah, MD, deputy commissioner for Medical and Scientific Affairs at the FDA, the federal agency can review these trials, resist the intense pressure to do things in a hurried or sloppy fashion, and get all of its normal work done as well, while still adhering to rigorous scientific and medical standards.

“The agency continues to review submissions of medical products while balancing the added workload of hundreds of additional COVID-19 related submissions,” he said.

Many of the companies that have developed biosimilars and submitted biologics license applications to the FDA have paid fees to the agency and expect their product reviews to take place in a timely fashion. In a media conference aimed at reassuring the public this week, Shah promised that would happen.

“The agency remains on target to meet our user fee goals for drugs this year by reviewing and taking timely action on over 90% of branded generic and biosimilar drug applications, even during the pandemic,” he said.

There are over 70 biosimilar development projects that the FDA is involved with currently. It is also working to 

 a system for calculating user fees for biosimilar applications so that the FDA has sufficient revenues to complete these tasks. Previous user fee calculations have been plagued by imprecise methodology that could not clearly anticipate 

, but based fee assessments on prior years’ activity, leading to shortfalls.

So far this year the FDA has approved 2 biosimilar products for marketing, and with just 4 months left in the year it is unlikely to equal the pace set last year, when it approved 10 biosimilars.

Granted, this year is an exception, and the FDA has more on its plate than it could have anticipated at the close of 2019. Still, the break with scientific and medical restraint that led the Russian Ministry of Health earlier this month to approve a COVID-19 vaccine after it was tested in just 76 people is unlikely to happen in the United States, based on Shah’s reassurances that the FDA will do things by the book.  

“The agency doesn’t sponsor clinical trials like the National Institutes of Health, nor does the agency develop tests like the Centers for Disease Control, nor does the agency invest in companies to accelerate the development of medical countermeasures, like the Biomedical Advanced Research and Development Authority. The FDA is a regulator, and as a regulator, the FDA is responsible to ensure the safety of consumers by rigorously evaluating the evidence about the benefits and risks of medical products,” Shah said.

In March, President Trump signed a $2 trillion emergency response 

 of which $80 million went to the FDA for COVID-19 response efforts, including the development of medical countermeasures and vaccines, promotion of advanced manufacturing of medical products, and monitoring of the medical product supply chain. A $3.2 billion overall fiscal 2021 budget for the FDA is under congressional review and includes an increase of $40 million from current year appropriations; however, the Alliance for a Stronger FDA has 

 the agency will need even more resources in the coming fiscal year. The Alliance encompasses patient advocates, trade groups, the biomedical research community, and medical community members.

Products under investigation as COVID-19 therapeutics include antivirals, immunomodulators, neutralizing antibodies, and more.

Even with such a mountain of data poised to flow into the FDA in the form of product approval applications, the agency is “prepared to review data on a real-time basis and to render judgements with unprecedented speed, while at the same time apply the same standards for safety and efficacy that we apply to all therapeutics,” Shah said.

He also promised that all review processes would be “unbiased and highly transparent.”

Shah provided numerous examples of how the FDA has already responded with promptness and exactitude to get COVID-19 testing kits into circulation, approve the first therapies specifically for COVID-19, such as remdesivir, and ensure that enough masks and other protective equipment are distributed to medical workers and others in high-risk positions.

Although addressing COVID-19 is the primary need, there is a simultaneous effort at the FDA to thwart the circulation and promotion of counterfeit cures, an underworld phenomenon that has led to 1000 fraudulent medical products for COVID-19 so far, Shah said. The FDA has issued more than 100 warning letters to companies “selling unapproved, unauthorized, or unclear products.” It has also worked with online retailers to root out and eliminate these products to protect the public.

Many efforts are under way, he said, to shore up the FDA’s response capability and also to learn from this crisis, so that it has the infrastructure and knowledge base fully poised to get a jump on the next public health emergency.

“While all of us want the world to return to normal as quickly as possible, it's imperative that we do this process credibly and transparently and that the public has confidence in our decisions,” Shah said.

The buck stops with the FDA when it comes to approving coronavirus disease 2019 therapeutics applications, said Anand Shah, MD, deputy commissioner for Medical and Scientific Affairs at the FDA.

FDA Reassures on Biosimilar Progress as COVID-19 Applications Pile Up

The European Commission (EC) has given marketing approval for the bevacizumab biosimilar Aybintio, by Samsung Bioepis.

The Incheon, Republic of Korea—based company said the EC has indicated the drug for the treatment of metastatic carcinoma of the colon or rectum, metastatic breast cancer, non–small cell lung cancer, advanced or metastatic renal cell cancer, epithelial ovarian, fallopian tube and primary peritoneal cancer, and cervical cancer. These encompass all approved indications for the reference product, Avastin.

The company noted the drug was approved based on analytical, pharmacokinetic, and clinical data, as well as pharmacology and toxicology data, all of which demonstrated that Aybintio and the reference product are highly similar with no clinically meaningful differences.

“Approval of Aybintio provides another treatment option for patients with certain types of cancers, enabling wider access to those in need,” said Christopher Hansung Ko, president and CEO of Samsung Bioepis, expressing pride in the drug authorization achievement.

Samsung Bioepis now has 5 biosimilars approved for use in Europe. These include Benepali (etanercept), Flixabi (infliximab), 

 for approval by Europe's Committee for Medicinal Products for Human Use.

Samsung Bioepis' latest approval gives it 5 biosimilar approvals in the European marketplace.

Samsung Bioepis' Bevacizumab Is Cleared for Launch in Europe

Much has been made of treatments for advanced coronavirus disease 2019 (COVID-19) infection, but early-stage treatments such as monoclonal antibodies (mAbs) and direct-acting antivirals (DAAs) are showing promise, said Anthony S. Fauci, MD, director of the National Institute of Allergy and Infection Diseases, in 

Among mAbs, for instance, the infliximab biosimilar Remsima is undergoing 

 in the CATALYST study for treatment of COVID-19 related inflammation. The Celltrion Healthcare drug has previously been employed for inflammatory conditions, which investigators believe makes it a promising candidate for treatment of COVID-19.

DAAs target specific virus proteins and disrupt viral replication and infection. Also showing promise, Fauci said, are convalescent plasma and hyperimmune globulin, therapies that involve antibody-laden blood taken from patients who have recovered from COVID-19. “There’s a lot of drugs and interventions that are actually being tested right now,” he said.

Although those are largely experimental, there is sound progress in treatment of late-stage disease, Fauci noted. Two drugs have been shown in placebo-controlled trials to have a beneficial effect in advanced disease. One is the antiviral remdesivir, which has significantly reduced time to recovery and hospital discharge, and the second is dexamethasone, an anti-inflammatory that has reduced the death rate in patients with COVID-19 not yet on ventilators but who need supplementary oxygen. These drugs are already recommended by guidelines-setting authorities for treatment of COVID-19, Fauci said.

Against the global backdrop, the United States has at times been exemplary for how not to manage the spread of COVID-19, but Fauci said he and others are in regular, weekly consults hosted by the World Health Organization to share information and experience.

“We have scientific collaboration with colleagues in the European Union, Australia, Canada, and Mexico. We have clinical trial networks in South Africa, Brazil, Chile, and Peru. So, there’s an awful lot of international activity going on. You don’t hear very much about that…, but it’s going on rather intensively," he noted.

Based on the progress, should schools be opening in the United States? Fauci said it all depends.

“The genuine default condition should be to try as best as you can to open up the schools for the reasons that the American Academy of Pediatrics has articulated very well: the psychological health of children, sometimes dependent on nutrition for breakfasts and lunches, and the secondary, downstream ripple effects that are negative for the families that might have to interrupt work to take care of the kids,” he said.

That said, it’s necessary to maintain the health of parents, relatives, and teachers as well as children, and “we live in a big country that has different levels of infection in different regions, states, cities, counties.” Some areas have less than 5% test-positivity for COVID-19 infection, and so you can open schools there “with relatively little impunity,” he said.

In areas with 5% to 10% test-positivity, there are CDC guidelines to help determine how to open schools and still protect school children and prevent the spread of infection. For areas in the “red zone” with greater than 10% test-positivity, “you really better think twice before you do that, because what might happen is you go in, people get infected, and—Boom!&mdash;they close them down,” he said.

“The bottom line is we live in a big country and we can’t take a unidimensional approach. Taking the country as a whole won’t work. We’re so heterogeneous,” Fauci said.  

In other pandemic clinical developments, biosimilar interferon beta-1a (IFN-β-1a, ReciGen) has shown 

 in helping to reduce symptoms and achieve virological clearance in patients with COVID-19.

Monoclonal antibodies may play a frontline role in dealing with COVID-19 infections, according to Anthony S. Fauci, MD.

Fauci Discusses Experimental COVID-19 Drugs and School Openings

Results of a subset of pediatric patients enrolled in a postmarketing surveillance 

 of biosimilar somatropin (Omnitrope) demonstrate that the recombinant growth hormone was safe and effective, investigators reported in an update to the PATRO Children trial.

Although marketed as a biosimilar in Europe, Omnitrope was approved via a new drug application under the Hatch-Waxman Act in the United States. The Sandoz product references Pfizer’s Genotropin. Results were presented for a subpopulation of patients (n = 291) recruited in Italy, with a mean age of 10 years (56% male).

Omnitrope is indicated for growth deficiency conditions in infants, children, and adolescents, such as Turner syndrome, chronic renal insufficiency, and Prader—Willi syndrome (PWS).

Patients received somatropin treatment for an average of 33.1 months and reported 48 adverse events (AEs), with a suspected relationship to the drug in 35 (12%) patients. Those AEs were most commonly headache, pyrexia, arthralgia, insulin-like growth factor above normal, abdominal pain, acute gastroenteritis, and pain in extremity.

Given prior concerns about a potential link between somatropin and diabetes development, the investigators said they were alert to possible incidence of type 1 or type 2 diabetes but found none, although 2 patients had impaired glucose tolerance that was linked to Omnitrope.

They measured the effectiveness of somatropin according to height standard deviation scores (HSDS) and height velocity standard deviation scores (HVSDS). Mean HSDS increased from −2.41 (0.73) at baseline (n = 238) to −0.91 (0.68) at 6.5 years of treatment (n

= 10). Mean HVSDS increased from −1.77 (1.38) at baseline (n

= 10). Scores were different for males vs females.

The primary end point was long-term safety in infants, children, and adolescents, including in patients with PWS, and a secondary end point was long-term effectiveness.

Most patients (95.5%) were treatment naïve to hormone therapy at enrollment. At the time of analysis, treatment had been discontinued in 140 of the 291 patients. Reasons for discontinuation included patients reached final bone/height maturation (32.9%), switched to other growth hormone drugs (15%), did not respond (2.9%), experienced AEs (2.1%), and failed to comply with treatment (1.4%). Investigators said follow-up was not possible for 13.6% of patients.

Among 43 AEs with a suspected relationship to the drug, 10.7% were mild and 1.4% were moderate in intensity. Complete resolution was reported for 34 AEs (8.6%).

The investigators reported 35 serious AEs in 7.2% of patients (n = 21). The 2 serious AEs included 1 patient with gait disturbances and worsening walking difficulties and another patient with a minimal increase in a known residual craniopharyngioma, a resurgence that was not definitively linked to the somatropin biosimilar.

Investigators said HSDS and HVSDS appeared to increase from 6.5 to 8.5 years of treatment, but the number of patients during this interval (<10) was low so they did not do a formal analysis.

At 3 years of treatment, patients with Turner syndrome had the highest HSDS and HVSDS. At 6.0 years of treatment, patients born small for gestational age had higher HSDS and HVSDS compared with patients who had growth hormone deficiency.

HSDS was lower in males than females at 3 years of treatment (−1.48 vs −1.43) and 6 years (−0.95 vs −0.85), but HVSDS was higher in males than females at 3 years (1.19 vs 1.11) and 6 years (1.44 vs 0.94).

No new safety signals were discovered during the study, and the investigators concluded the biosimilar was effective and well tolerated over the long term (8.5 years).

Lughetti L, Antoniazzi F, Giavoli C, et al. Safety and effectiveness of a somatropin biosimilar in children requiring growth hormone treatment: second analysis of the PATRO Children study Italian cohort. 

. Published online June 15, 2020. doi:10.1007/s40618-020-01331-4

A postmarketing surveillance study of Omnitrope in pediatric patients with growth hormone deficiency sheds new light on how this agent performs relative to its reference product.

PATRO Study Supports Omnitrope for Growth Deficiency

The current biosimilar-generated savings in the US health care market is $4.1 billion, as opposed to $10.3 billion in potential savings, according to Wayne Winegarden, PhD, a senior fellow in Business and Economics at the Pacific Research Institute (PRI) in San Francisco and director of PRI’s Center for Medical Economics and Innovation.

“The bad news is that the growth [of biosimilars] that has occurred pales in comparison to what we could be accruing,” said Winegarden at a recent employer issues webinar hosted by the Pacific Business Group on Health and the Integrated Benefits Institute.

Partly how to accomplish the full $10.3 billion in savings is by allowing all 9 classes of approved biosimilars to enter the market, he said. Currently, adalimumab and etanercept biosimilars are held back by patent protections on originator products.

Winegarden held up the example of generic drugs as an illustration of how drug price trends can be tamed by the introduction of lower-cost alternatives.

In the United States, national health expenditures have been soaring. From 1960 to 2018, the average annual growth rate was 8.8%, and the rise in cost for prescription medicine has not been that far behind: 8.7%. But the rise of generic medicines has made a difference. From 2017 to 2018, the annual growth rate of national health expenditures was 4.6% and the rate of increase in prescription drugs was 2.5%, Winegarden noted.

Generics save the health care system $292.6 billion annually, but that cost suppression effect is not happening yet with biosimilars, he said.

“Biologics are very important in terms of their health impact. They have led to significant increases in our survival rates for cancer. But we’ve gotten to the point where competition should be coming in and controlling costs, like we saw in the generic market, but we’re not seeing that develop,” and because of that phenomenon, that’s where that $10.3 billion in savings is being left on the table. We have some types of market obstructions that are stopping that competitive process from controlling drug expenditures,” Winegarden said.

The 2019 overall increase in net specialty drug spending, which includes biologics and biosimilars, was 11.6% vs -5.0% for traditional drugs, and 2.3% overall, Winegarden said. From 2017 to 2018, the increase in biologics and generics spending in the United States was $10.9 billion and $3.91 billion, respectively, he said, citing IQVIA data.

By contrast, biosimilars command a greater than 50% share of the market for biologics in the European Union. In 5 European Union countries, epoetin alpha biosimilars have a 100% share of the market and a 66% average share across 24 countries in that zone. This competition has resulted in a 27% decline in the price of epoetin alpha prior to the market entry of these biosimilars.

However, in the United States, where biosimilars are considered far behind those in Europe, some of the price discounts they have achieved are dramatic, nonetheless. The cost of infliximab has declined 45% since these biosimilars arrived on market; pegfilgrastim, 24.7%; epoetin alpha, 29.6%; and filgrastim, 52.6%, Winegarden said.

Still, total market share is slender overall. Other than for filgrastim, biosimilars each represent less than one-fifth of the market for their respective drug types in the United States, Winegarden said.

“This demonstrates that when we talk about drug affordability problems, we’re talking about the lack of biosimilars in the biologics market,” he said.

In a recent interview with The Center for Biosimilars®, Winegarden discussed the 

A Pacific Research Institute economist says that by his scorecard, biosimilars are not supercharging the market the way they ought to be doing .