Tony Hagen is senior managing editor for The Center for Biosimilars

Tony Hagen

As the deadline approaches for HHS to divulge its game plan for controlling prescription drug costs  and “price gouging,” levels of concern are rising among providers and manufacturers.

A group of 16 patient advocacy organizations has asked CMS and HHS to consider establishing a zero co-pay policy for Medicare Part B patients, a move the groups said would improve access to biosimilars and save seniors in Medicare as much as $3 billion in out-of-pocket costs.

“Alignment of incentives across Medicare programs that encourage the use of biosimilars are integral to the development of the US market, leading to increased biosimilar usage and unlocking immense savings in the US health care system,” the group said in an open letter to HHS and CMS officials.

The letter was signed by the Allergy & Asthma Network, CancerCare, Consumer Action, Crohn’s & Colitis Foundation, Endocrine Society, Healthy Women,, International Myeloma Foundation, Lupus Foundation of America, and others.

HHS to produce a policy for combating high prescription drug prices as soon as Monday, August 23.

The advocacy groups, in their letter, acknowledge the high cost of biologics, which are made from living organisms and require extensive, carefully controlled processes to develop and manufacture. 

Biosimilars are lower-cost alternatives to originator biologics and have no clinically meaningful differences when it comes to safety or efficacy, according to the FDA. “These therapies represent an opportunity to improve the health and well-being of millions of Americans and, at the same time, save US taxpayers billions in health care costs," the advocacy groups said.

Nearly 15% of Medicare Part B enrollees pay the full 20% coinsurance for their reference biologic, while others have supplemental insurance that only covers a portion of the 20%.

US patients have had access to biosimilars for 6 years; 30 of them are now approved and 21 are on the market. Medicare “enrollees can face thousands of dollars in annual out-of-pocket costs for biologics, creating affordability and access barriers for patients in Part B. Nearly 15% of Medicare Part B enrollees pay the full 20% coinsurance for their reference biologic, while others have supplemental insurance that only covers a portion of the 20%,” the letter states.

The group estimates that a zero co-pay policy would save taxpayers $5 billion over 10 years.

Other signatories to the letter included Beyond Type 1, DiabetesSisters, National Consumers League, Patients Rising Now, Rheumatology Nurses Society, Sjögren’s Foundation, and ZERO - The End of Prostate Cancer.

Articles

A group of 16 advocacy groups are urging HHS to make zero co-pays for biologics a part of its prescription drug price reform program. 

Advocacy Groups Call for Zero Co-pay Policy on Biosimilars

Results of a phase 3 trial of bevacizumab biosimilar candidate FKB238 suggest the monoclonal antibody is comparable in efficacy and safety to the reference product (RP), Avastin, in patients with advanced/recurrent nonsquamous non–small cell lung cancer (non-sq-NSCLC).

FKB238 is a pipeline drug from Centus Biotherapeutics, a joint venture between AstraZeneca and Fujifilm Kyowa Kirin. FKB238 (Equidacent) is approved for marketing in the European Union but remains under review by the FDA. In April 2021, Centus reached a 

, patients were randomized 1:1 to intravenous infusions of FKB238 or RP at a dosage of 15 mg/kg. All patients received infusions of paclitaxel 200 mg/m

 and carboplatin for 4 to 6 cycles prior to receiving the bevacizumab agents. Patients received bevacizumab on day 1 of each 21-day cycle until disease progression or discontinuation of therapy.

The primary end point was overall response rate (ORR), which investigators described as a more appropriate measure of efficacy for biosimilar comparisons than overall survival (OS).

They chose a patient population with advanced/recurrent disease because this best matched the population for whom efficacy was demonstrated in the original study of Avastin.

The ORR rate was 51.6% in the FKB238 arm (n = 364) and 53.7% in the RP arm (n = 367). Estimated median progression-free survival (PFS) was 7.72 months in the FKB238 arm vs 7.62 months for the RP group (HR, 0.97; 95% CI, 0.82-1.16).

The occurrence of treatment-emergent adverse events (TEAEs) for patients receiving FKB238 vs RP was 94.2% and 95.1%, respectively. Investigators said 53.6% and 55.5% of patients in the FKB238 and originator arms experienced grade 3 or higher TEAEs, respectively.

Patients with non-sq-NSCLC typically present with inoperable, locally advanced, or metastatic disease, which is incurable, although with the introduction of kinase inhibitors and immune checkpoint inhibitors 5-year survival has improved to about 25%.

Serious TEAEs were experienced by 25.1% of patients in the FKB238 arm and 26.0% of patients in the RP cohort.

Patients with non-sq-NSCLC typically present with inoperable, locally advanced, or metastatic disease, which is incurable, although with the introduction of kinase inhibitors and immune checkpoint inhibitors, 5-year survival has improved to about 25%. Bevacizumab has been effective in prolonging PFS in non-sq-NSCLC. It is an angiogenesis inhibitor, meaning it retards the growth of blood vessels that feed tumor growth.

An earlier, phase 1 study of FKB238 demonstrated pharmacokinetic properties comparable to the originator product and good tolerance by patients, without antidrug antibody development.

In AVANA, median OS was 14.13 months for patients receiving FKB238 (95% CI, 12.52-16.56) and 16.95 months for patients in the RP arm (95% CI, 14.65-19.02). Investigators said 3% of patients in each arm tested positive for antidrug antibodies at any visit.

There are currently 2 bevacizumab biosimilars on the US market: Mvasi (Amgen) and Zirabev (Pfizer), launched in July 2019 and December 2019, respectively.

Centus Biotherapeutics reports positive findings from AVANA for its bevacizumab biosimilar candidate. 

Centus Bevacizumab Candidate Demonstrates Equivalence in Phase 3 Study

If biosimilars development and sales have lost some of their luster for Pfizer, it’s understandable, given the tremendous boost to the bottom line the company has received from its COVID-19 vaccine. The Pfizer-BioNTech COVID-19 vaccine contributed $7.8 billion in revenues during the second quarter of 2021, and the company said in its 

 that its vaccine business was just getting started, with new contracts being signed for delivery around the globe.

The vaccine paycheck literally dwarfed the company’s biosimilars revenue—$559 million for the second quarter of 2021, even though this was up 88% compared with the same quarter a year ago. However, in its earnings discussion, the company said it was not actively seeking to expand its biosimilars product portfolio and saw more attractive opportunities in pharmaceutical development elsewhere, particularly in innovative, or novel, medicines.

“Certainly, we've been so pleased with the tremendous growth that we've seen [for biosimilars] and the deep utilization of our biosimilars,” said Angela Hwang, MBA, group president of Pfizer’s Biopharmaceuticals Group. “We've made [a] pivot to a pure play sort of innovation focus in our pipeline. We are really now looking at that biosimilar portfolio vis-à-vis other investments in breakthrough therapies. We will continue to look for opportunities, but I would say at this point it’s going to be more opportunistic.”

And if that wasn’t clear enough, Albert Bourla, PhD, chairman and CEO, explained in the same conference call that Pfizer can 

 about its investments and is putting its money on original medicines. “Right now, we are clearly focusing on first-in-class, and particularly, best-in-class first-in-class.”

At the moment, Pfizer does not have any biosimilars in its 

. Bourla said the company is especially interested in developing Janus kinase (

for treatment of inflammation. It has 2 JAK inhibitors in the FDA submission (registration) stage currently (abrocitinib, PF-04965842; tofacitinib, Xeljanz), for atopic dermatitis and ankylosing spondylitis, respectively, and 1 in phase 3 clinical development (ritlecitinib, PF-06651600), for alopecia areata, although these are not biosimilars.

Pfizer has multiple other products under the internal medicine, rare disease, and oncology headings that are in the phase 3 or registration stages of development, as well as development-stage vaccines for COVID-19, pneumococcal infections, and tick-borne encephalitis. Again, these are not biosimilars.

Not as far along in development, and also not a biosimilar, is a Lyme disease vaccine, in phase 2 clinical development, which Pfizer is co-developing with Valneva. The companies are seeking to determine the optimal dosing schedule to be applied in a phase 3 study, which would potentially initiate in the first half of 2022.

We are really now looking at that biosimilar portfolio vis-à-vis other investments in breakthrough therapies. We will continue to look for opportunities, but I would say at this point it’s going to be more opportunistic.

Pfizer last launched new biosimilars in late 2019 and 2020, when it began the marketing of bevacizumab (Zirabev), rituximab (Ruxience), and trastuzumab (Trazimera) biosimilars.

Pfizer’s commitment to biosimilars was challenged from the beginning, when in 2017 it launched the infliximab biosimilar Inflectra and immediately ran into a barrage of tactics from Johnson & Johnson that, Pfizer claimed, effectively stunted sales growth for Inflectra. Biosimilars in the infliximab class became the worst-performing group by market share. Although infliximab biosimilars were launched as early as 2017, they had taken just a 23% market share from the reference product, Remicade, by the first quarter of 2021. Biosimilars in other categories had done far better, with filgrastim biosimilars doing the best (73% market share).

In a legal battle with J&J over Inflectra’s weak launch, Pfizer alleged 

; in particular, Pfizer alleged that J&J was strong-arming payers by threatening to withhold rebates unless they agreed to “biosimilar exclusion” contracts. The case was resolved in July 2021 with an undisclosed settlement between the litigants; and although Pfizer said it was going to stick it out in the inflectra biosimilar business, it has been hard-earned money compared with the COVID-19 windfall.

Despite the positive biosimilar revenues this past quarter and the lukewarm interest in developing further biosimilars, Pfizer has been at wider extremes in the past year in its commitment to this class of biologics. The company clung tight to its biosimilars portfolio when it spun off its Upjohn division to 

, which represents the combined forces of Upjohn and Mylan, a biosimilars development company with at least 20 biosimilars and insulin analogs in its portfolio. The move suggests Pfizer clearly values the biosimilars it has.

The Upjohn division trade included Lipitor (atavastin), the blockbuster cholesterol drug; and Viagra (sildenafif citrate), the popular erectile dysfunction drug.

 it was abandoning its biosimilars manufacturing plant in Hangzhou, China. Starting in 2016, the company had begun a $350 million investment to develop the plant for the sake of producing biosimilars for the China market. The company did an about-face this spring, when it announced it had reached the “difficult decision” to pull out of that investment and sell the entire plant to China-based WuXi Biologics, a biopharmaceutical company with global activities.

And this time last year, New York-based Pfizer was publicly expressing disappointment with the state of the biosimilars market in the United States. “The 

 is the low uptake of biosimilars in the United States,” said Juliana Reed, MS, a vice president and Global Corporate Affairs lead for Pfizer, in a presentation for the Pacific Business Group on Health and the Integrated Benefits Institute. Although the United States consumes 60% of the biologics produced globally, 90% of biosimilar sales occur in the European Union, Reed said.

“We know we have to address anticompetitive behaviors that disincentivize the uptake of biosimilars, but we also need proactive policies that incentivize the uptake of biosimilars," Reed said.

After the loss of a manufacturing plant in China and a knock-down-drag-out battle with Johnson & Johnson, is Pfizer cooling on biosimilars?

Pfizer Changes to "Opportunistic" Stance on Biosimilars

As clinical evidence accumulates on single-agent use of biosimilars in oncology and other settings, providers are also interested to know how these agents perform in combination with other therapies, where it may be possible to reduce costs of care with the introduction of biosimilar agents. 

Trastuzumab reference product (RP; Herceptin) in combination with pertuzumab (Perjeta) has become standard of care for first-line treatment of stage II/III human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer. Overexpression of the protein HER2 is associated with cancer cell proliferation, and trastuzumab and pertuzumab bind to HER2 and suppress this growth.

(N = 42), investigators compared simultaneous administration of trastuzumab biosimilar (Kanjinti; ABP 980) and pertuzumab vs trastuzumab RP plus pertuzumab, both administered via admixture in an intravenous (IV) bag. 

As combination therapy of trastuzumab RP plus pertuzumab has become the standard of care for first-line treatment of late stage (stage II to stage III) HER2-positive metastatic breast cancer, an admixture of trastuzumab RP plus pertuzumab in a single 250 mL infusion bag is more efficient for patients and caregivers than 2 separate 250 mL infusions.

Use of an admixture of trastuzumab and pertuzumab is considered more efficient than administration of each drug through separate, consecutive infusions. Findings from LAVENDER published this month demonstrated safety and tolerability for ABP 980 and pertuzumab delivered from a single IV infusion bag, authors of the study wrote.

Healthy men were randomized 1:1 to IV pertuzumab 420 mg and ABP 980 6 mg/kg or an identical combination of trastuzumab RP and pertuzumab. The participants were followed for 92 days post dosing.

The resulting serum concentrations of the biosimilar and RP were comparable and there were no serious adverse events (AEs), deaths, or cardiac disorders, investigators said. No participants developed antidrug antibodies. “There were no notable differences between treatment groups in the severity of AEs and there were no events greater than grade 2 in severity,” they wrote.

The study was initiated with 42 enrollees, but a problem with air bubbles forming in IV lines caused the infusion pump to stop, which interrupted IV administrations for 5 of the first 6 enrollees. The problem was identified as being related to prior refrigeration of the agents and was solved by allowing the solutions to warm to room temperature (3 hours) prior to administration. The problem was not unique to either the biosimilar or RP admixture, study authors said.

Because of this event, data for the first 6 participants were not included in the final analysis, although the AE profile for these individuals was consistent with the main analysis. Data for 18 participants in each cohort were included in the assessment (n = 36).

Multiple prior studies have served as the foundation for LAVENDER.

, trastuzumab RP and pertuzumab administered as sequential IV infusions demonstrated safety and tolerability in patients with metastatic HER2-positive breast cancer who had experienced disease progression during prior trastuzumab therapy. The objective response rate was 24.2% and the clinical benefit rate, a measure of complete response, partial response, and stable disease rates, was 50%.

 (CLEOPATRA), patients received paclitaxel plus trastuzumab RP plus pertuzumab sequentially and intravenously. The 6-month progression-free survival rate was 86%, which was well above the minimum for success of 65%.

 study, patients were administered vinorelbine in combination with trastuzumab RP and pertuzumab for the first-line treatment of HER2-positive breast cancer. This dosing was given both sequentially and via co-infusion (admixture) of trastuzumab and pertuzumab, followed by vinorelbine. There were no meaningful differences in outcome between the 2 cohorts, which LAVENDER authors said offered support for combining trastuzumab and pertuzumab in a single-bag infusion.

“The results of the LAVENDER study…demonstrate that administration of the biosimilar ABP 980 plus pertuzumab in a single 60-min IV infusion is safe and feasible,” the authors concluded. "The resulting [pharmacokinetics] of ABP 980 and trastuzumab RP were not affected by the co-infusion.”

The LAVENDER study demonstrates safety and tolerability of simultaneous intravenous (IV) administration of biosimilar trastuzumab (Kanjinti) and pertuzumab in cohorts of healthy volunteers.

Trastuzumab-Pertuzumab IV Admixture Demonstrates Safety, Tolerability

After issuing a number of directives in July targeted at lowering the cost of prescription drugs and getting biosimilars into play, President Biden has clarified his intentions with a request for Congress to take action on specific measures.

The request endorses passage of the Elijah E. Cummings Lower Drug Costs Now Act, which would enable HHS to negotiate prescription drug prices for Medicare beneficiaries and, if companies refuse to negotiate, would limit drug prices to 120% of average prices in Australia, Canada, France, Germany, and the United Kingdom.

from the House Committee on Oversight and Reform that noted steep price increases for the rheumatology drug adalimumab (Humira) and contended these were excessive and unjustifiable.

, Biden directed the FDA to set up a means by which lower-cost pharmaceuticals could be imported from Canada. It directed HHS to increase support for generic and biosimilar drugs and asked HHS to develop a comprehensive plan for combating high prescription drug prices and price gouging. It also called upon the Federal Trade Commission to ban so-called pay-for-delay tactics that originator companies use to forestall competition for their most lucrative products.

Under the timeline Biden gave HHS to submit a plan for lowering drug costs, the report would be due in about 10 days, or August 23.

“For every other type of health care service, Medicare works to get the best prices for American seniors. But for prescription drugs–and only prescription drugs–Medicare is prohibited by law from negotiating for the best deal. This needs to change,” the Biden letter to Congress 

Biden also calls for caps on out-of-pocket costs for Medicare beneficiaries and recommends a penalty for drug companies “that raise their prices faster than inflation.”

The Cummings bill, HR 3, was first introduced in 2019 and reintroduced in April 2021. It would allow HHS to negotiate with pharmaceutical companies over the prices of high-cost drugs for which there is no generic or biosimilar competition. HHS would start in 2024 by negotiating prices for 25 of the drugs with the highest spend and at least 50 more drugs “in following years.” These negotiations would include insulin products.

“If pharmaceutical companies refuse to negotiate, they would face civil and tax penalties,” according to the Center for American Progress (CAP), a liberal research and advocacy group cited by Biden in his message to Congress.

According to CAP, US drug prices are on average 2.56 times those in 32 peer counties. Under HR 3, if international prices cannot be obtained for drugs HHS wishes to negotiate, the agency would be permitted to set the price at 85% of the average manufacturer price.

The Congressional Budget Office estimates that savings from HR 3 would amount to almost $500 billion over a decade, according to CAP. Specifically, the cost for a 30-day supply of adalimumab and etanercept would be reduced by $2161 and $2086, respectively.

CAP said HR 3 would cap out of pocket drug costs for Medicare beneficiaries at $2000, down from the current $6550 out-of-pocket limit before catastrophic coverage kicks in under Medicare Part D.

The Biden letter to Congress was applauded by the Biosimilars Forum, a group of biosimilar manufacturers. We urge Congress to pass meaningful legislation that gives more patients access to lifesaving, lower-cost biosimilar therapies so we can realize the Affordable Care Act’s full potential to lowering drug costs,” said Meaghan R. Smith, executive director of the Biosimilars Forum.

For a legal perspective on Biden's pharmaceutical pricing initiatives, click 

Passage of HR 3 is shaping up as a centerpiece of President Biden's effort to bring pharmaceutical prices under control. If drug companies won't negotiate prices, international reference pricing would kick in. 

Biden Asks Congress for Support on Pharmaceutical Price Controls

Most payers tend to adopt a “wait and see” approach to promoting biosimilar switching strategies among providers, according to a 

The approach calls for watching what other payers do rather than initiating switching incentives via policy requirements, according to payers who participated in the study.

However, the payers agreed that getting providers to switch to a new biosimilar requires careful market preparation that targets physicians, health systems, pharmacists, and patients.

“Discussions with network physicians about a biosimilar switch started several months before the formulary change to reach mutual agreement across stakeholders,” according to one payer participant cited in the survey.

Physicians were given educational materials about safety, efficacy, and potential cost savings, and pharmacists and patients were called by phone and notified about the coming biosimilar switch.

Targeted education for providers about safety, efficacy, and biosimilar interchangeability data was identified as a major component to increase confidence in prescribing these agents.

There was also a 90-day prior notification of the formulary change and, authors of the study said, the prior authorization process was removed or accelerated. With these targeted initiatives, the payer group was able to reach a 90% biosimilar adoption rate among its patients.

Expediting prior authorizations was, in fact, a top recommendation of providers who participated in surveys that provided the basis for the focus group discussion. Authors said 80% of participating physicians felt expediting prior authorizations would simplify access to biosimilars and result in an uptick in biosimilar usage; 69% of managed care pharmacists (MCPs) concurred with this viewpoint.

The focus group panel consisted of 5 MCPs and 3 physician experts in rheumatology, dermatology, and gastroenterology from large managed care organizations and health care systems in the Boston region.

Two surveys involving 300 managed care and specialty pharmacy professionals and 48 providers served to inform the focus group discussion. The surveys were conducted by PRIME Education and the Academy of Managed Care Pharmacy.

“The panel agreed that removing administrative burden from prior authorization requirements was necessary to increase biosimilar adoption,” authors of the report said. Other means of incentivizing biosimilar uptake also were discussed.

The authors cited a recent study of Medicare formulary placement, which showed prescription drug plans tend to place biosimilars and their reference products on the same cost-sharing tiers and require prior authorization at the same frequency, “providing little incentive for biosimilar adoption.”

Providers also reported the need to understand the
incentives attached to prescribing biosimilars and expected deeper discounts for biosimilars in comparison with the reference product.

More communication with payers is essential to facilitate biosimilar adoption, the focus panel concluded. This includes transparent pricing information about formulary placement and biosimilar pricing, along with point-of-care information on cost savings.

“These strategies could drive provider’s willingness to prescribe biosimilars and support conversations with patients about biosimilar switches,” the authors wrote. Cost-benefit transparency would also boost trust among providers, payers, and patients, they said.

Other strategies for biosimilar adoption that scored high on the approval tree among providers and MCPs were educational programs for prescribers that focused on evidence for switching to biosimilars (MCPs, 91%; providers, 92%) and educational programs covering real-world evidence from postmarketing studies, including in the European Union (MCPs, 86%; providers, 88%).

“For biosimilars, postmarketing surveillance studies are pivotal in establishing the safety, efficacy, and immunogenicity profile compared with the reference product,” the authors wrote. For example, the NOR-SWITCH study of patients with immune-mediated inflammatory diseases has been of great value because it demonstrated the noninferiority of switching from originator infliximab to its biosimilar compared with remaining on the originator product, they wrote.

Although physicians ought to be reassured by confirmatory surveillance studies and long-term real-world safety data, surveys suggest physicians’ biosimilar prescribing confidence remains low, the authors said. “At the focus group meeting, there was consensus regarding the substantial need for provider education about biosimilar use in clinical practice.”

Providers who participated in the focus group said biosimilar education would be best delivered by clinical pharmacists from the same institutions as providers. They said this education should be provided in grand round or small group presentations, and they recommended that it be tailored to physician specialties with clinical data provided for each disease condition.

Another means of incentivizing the use of biosimilars that survey participants strongly favored was adjusting fee schedules for biosimilars (MCPs, 68%; providers, 62%) and reducing cost sharing for patients using biosimilars (MCPs, 80%; providers, 79%).

“In fact, focus group providers believed that switching to biosimilars should be associated with tangible benefits to their practices [eg, higher reimbursement, money for additional staff hires] and patients,” the authors wrote.

“These steps require ongoing collaborative initiatives among multiple stakeholders to optimize use of biosimilars,” they concluded.

When it comes to their willingness to use biosimilars, providers and managed care pharmacists prefer greater transparency on formulary placement and costs, according to a focus group study based on health care surveys. 

Study: Payers Play Wait-and-See Game of Biosimilar Preference

Specialty drug spending grew at a slower pace from 2019 to 2020, marking the first time in 5 years that the trend of rising specialty drug costs moderated, according to a report from Artemetrx.

The report said the slower increase in specialty drug spending was likely due to delayed or deferred diagnostic care during the COVID-19 pandemic, increased biosimilar use, and the availability of more generic products.

“On a per-member-per-year basis [PMPY], specialty drugs across both the medical and pharmacy benefits spectrum averaged $959 [in 2020, up 11.8%], an average increase of $101 compared with an increase of $111 in the prior year,” according to the report.

However, the report’s authors said specialty spending varied widely by plan sponsor, ranging from $587 to $1065 PMPY.

Between 2019 and 2020, there was no increase in the percentage of plan members using specialty drugs. This rate, representing the percentage of members taking at least 1 specialty drug, stayed level at 4% for both years. In 2018, the rate stood at 3.7%.

Authors of the report noted that specialty drug costs can quickly escalate if the percentage of specialty drug users increases. An increase of 0.1% can result in a $2.4 million overall spending increase, based on a population of 100,000 plan members.

Although there was no increase in the percentage of specialty drug users, there was an increase in the number of specialty drug claims per user: 5.2 claims in 2020 vs 4.8 claims in 2019. This represented an 8.3% increase.

“Increases in the number of specialty drug utilizers and the average number of specialty claims per utilizer could result in an exponential trend in the coming years,” authors of the report said.

As the pandemic raged in 2020, the number of claims for home infusion treatment spiked, they said. The increase was 8.8% for the year, but there was unevenness during 2020, and the highwater mark was an 18.3% spike in home infusion claims in the second quarter of 2020. The low was in the first quarter, when home infusion claims rose just 3.1%.

The report noted significantly higher average costs per claim for specialty drugs administered in the outpatient hospital setting vs home infusion or the physician’s office, with the physician office being the most economical venue.

The outpatient hospital annual cost for infliximab (Remicade) was $94,525 and for pegfilgrastim (Neulasta), $109,825. The comparable costs for the home infusion vs physician office settings were $54,222 and $72,317 vs $48,844 and $61,103, respectively. Remicade and Neulasta are originator products and are generally considered more costly than biosimilar forms of infliximab and pegfilgrastim.

“The average plan could save between $77,811 and $94,403 by shifting these 2 medications from outpatient hospitals to home infusion or physician office sites of care,” the authors said.

The report anticipated a continuing increase in specialty drug spending PMPY over the next 2 years of about $100 or slightly above each year. The authors anticipated “low double-digit” year-over-year increases, which they said would likely be prompted by increased drug use and offset by cost management efforts, more use of biosimilars, and a trend toward greater use of the pharmacy drug channel. New products expected to reach market will also contribute to this effect, the authors predicted.

In terms of 2020 specialty drug spending, the following categories of drugs were at the top of the list 

For every plan member who shifts to a biosimilar for inflammatory disorders, the potential annual savings is $9973, the report said.

Biosimilars are taking a lot of market share from originator drugs, the authors said. For example, claims for the originator product Neulasta dropped roughly 35% from 2018 to 2020. Claims for Herceptin, the originator trastuzumab product, have dropped 40%, the study said.

Steep, but less impressive, biosimilar gains were seen in the bevacizumab, rituximab, and infliximab markets.

Infliximab biosimilars represented just 18% of infliximab claims in 2020, “but the downward effect on average sales price [ASP] is apparent. Since January 2019, the ASP per unit for Remicade has declined from nearly $75 per unit to $45 per unit at the close of 2020.”

Per-unit costs of Neulasta, an originator product, declined from $4500 in January 2019 to under $3500 in December 2020, a reflection of an increasing number of biosimilar options in this market.

The authors of the report modeled the potential savings in inflammatory disorders and oncology for patients receiving biosimilars, and they found the reduced cost would be significant.

“For a plan with 100 members taking infliximab, shifting 20% of members to a biosimilar would save nearly $200,000 per year, and shifting 50% of members would save nearly $500,000 dollars,” they said. The comparable savings for shifting 20% of 100 patients to pegfilgrastim biosimilar would be $87,780 and $219,450, respectively.

In some cases, manufacturer rebates for reference product use are highly competitive with rebates offered for biosimilars. The report said Remicade rebates averaged $9, which is within the rebate range for Inflectra, Renflexis, and Avsola ($10, $9, and $6, respectively).

Rebates for the originator pegfilgrastim Neulasta were $431, vastly higher than available for Udenyca, Fulphila, and Ziextenzo ($19, $70, and $45, respectively).

A report from Artemetrx details 2020 changes in demand for biosimilars and other specialty drugs, according to health plan spending. Dynamics that could affect future spending are also explained.

Report: Specialty Drug Cost Increase Eased a Little in 2020

Not quite a year old, Viatris, the company 

by the merger of Mylan and Pfizer’s Upjohn division, is banking heavily on its biosimilars portfolio and pipeline, which contain approved and marketed products as well as various product candidates in clinical development or under regulatory review.

The Canonsburg, Pennsylvania, company made headlines in July 2021 when the FDA upgraded its insulin glargine product (Semglee) to biosimilar and interchangeable status, meaning pharmacists could dispense Semglee without first obtaining physician clearance.

The product will be the first test of the FDA’s interchangeable designation, and biosimilar stakeholders will be watching to see whether interchangeability serves to boost uptake for Semglee, which was first approved in June 2020 as a nonbiosimilar rival to Lantus.

“Semglee is not the only [product] in our pipeline this quarter. With regard to our biosimilar and complex products pipeline, we're making steady progress across multiple programs,” Michael Goettler, CEO, said in an 

In the second quarter 2021 earnings conference, Viatris officials said they also have confidence in their aflibercept product candidate, which they hope to get through the FDA review process ahead of rival companies.

“There are a number of competitors going through this. We’re leading right now. We’re the first ones to finish a [phase 3] clinical trial,” Goettler said.

$333 million in combined biosimilar and complex generics sales for the quarter just ended, down 5% from $351 in the comparable 2020 quarter; however, biosimilar sales were up 40%. The overall sales decline in this combined category was attributed to generic drug competition.

The company, formed in November 2020, reported total sales of $4.56 billion, up from $4.35 billion in the (adjusted) year-ago quarter, a 5% improvement.

Viatris also reported complex generic and biosimilar sales by global region. In North America and the European Union, biosimilar sales for the quarter just ended were $309 million. The company is far less active in terms of biosimilar and complex generic sales in South and Central America, Africa, the Middle East, and Russia. The company reported second quarter 2021 sales of $14 million for these zones.

In Australia, Japan, and New Zealand, biosimilar and complex generic sales were $10 million, up 16%; and, so far, Viatris’ sales of biosimilars have not penetrated China.

Viatris has regulatory approvals for etanercept (Nepexto) and adalimumab (Hulio) biosimilars. In February 2021, Viatris launched Hulio in Canada and Japan. Hulio was launched in the European Union in 2018. The company’s etanercept product was launched in the European Union in 2020. Viatris is currently seeking regulatory approval for bevacizumab and insulin aspart biosimilar candidates.

Viatris has another insulin glargine product in preclinical development (referencing Toujeo; Sanofi), as well as an onabotulinumtoxin biosimilar (referencing Botox) in preclinical stage development.

The aflibercept biosimilar candidate is on the cusp of FDA regulatory submission, and this is scheduled for the fourth quarter of 2021, according to Rajiv Malik, president of Viatris.

For an article on expert views of the insulin market and biosimilars, click 

Semglee (insulin glargine) will be the first test of the FDA's interchangeability concept for biosimilars, but Viatris aims to grow its biosimilar revenues with multiple products.

Viatris Expresses Faith in Its Biosimilars Lineup

It all began in 2018 when, on prompting from former President Donald Trump, CMS 

 and allowed Medicare Advantage plans to use step therapy for Part B drugs—those that are administered in a doctor’s office. Step therapy, also known as fail-first therapy, entails payers requiring use of less costly therapeutics before patients are prescribed costlier medicines.

The policy most recently has been blamed for spurring a domino effect of policy changes among payers requiring eye physicians to prescribe the off-label use of bevacizumab for ocular conditions before significantly more costly FDA-approved products (ranibizumab, Lucentis; aflibercept, Eylea) can be used. The American Academy of Ophthalmology (AAO) has called this a de facto 

 in which patients are unwitting guinea pigs who face the risk of being prescribed ineffective or unsafe drugs.

Avastin, the bevacizumab reference product, has been used by eye doctors for 15 years based on what the AAO calls sound and ample clinical evidence, but bevacizumab biosimilars (Mvasi, Zirabev) have not been subjected to the same rigorous clinical testing in ocular disorders, and they ought to be, because there may be problems associated with their use in ophthalmology, the AAO contends. 

Further, many payers now treat bevacizumab biosimilars as equivalent to Avastin in their step therapy policies, and this is wrong, the AAO says.

The factors in favor of off-label Avastin use in such eye conditions as age-related macular degeneration, diabetic retinopathy, and retinal vascular occlusions are indeed clinical experience with this product and the cost advantage, according to Sonia Oskouei, vice president of Biosimilars for Cardinal Health. “It is a fraction of the cost of other current anti–vascular endothelial growth factor [VEGF] options.”

However, Avastin must be sent to compounding pharmacies to create the different dosage units required for intravitreal (in eye) injections, which Oskouei said can contribute to some providers preferring not to use it. The repackaging of bevacizumab has given rise to concerns about impurities that could be introduced during the process, sterility, and dosage consistency.

In addition, the off-label use remains a concern for some. “You typically have 2 camps of providers in this space—ones who feel comfortable using Avastin off-label and others who prefer only on-label use of FDA-approved treatment options (eg, Lucentis, Eylea),” she said.

At least one company, however, is attempting to bring a bevacizumab version to market that would be specifically indicated for ophthalmologic treatment. Outlook Therapeutics' bevacizumab candidate ONS-5010/Lytenava is undergoing evaluation in NORSE TWO, a phase 3 study (N = 228) of safety and efficacy in patients with neovascular age-related macular degeneration (wet AMD). The trial involves a comparison of ONS-5010 with ranibizumab.

Earlier this month, investigators said NORSE TWO met the 

 for the proportion of patients who demonstrated minimum improvement in best corrected visual acuity (BCVA) after 11 months of treatment. The percentage of patients in the intent-to-treat cohort who gained at least 15 letters in BVCA was 23% with ranibizumab and 41% with ONS-5010 (

One patient reported ocular inflammation in 3 trials: NORSE ONE, NORSE TWO, and NORSE THREE. In NORSE TWO, there was just 1 serious adverse event (AE) associated with the trial drug, and this was successfull

“No unanticipated safety signals were detected,” the authors wrote.

on AE was intravitreal injection–related hemorrhage in tissues on the surface of the eye, and these were successfully resolved. “The ONS-5010 safety database continues to be consistent with previously published results for bevacizumab, such as in the 2011 CATT clinical trial,” authors of the study wrote.

Outlook plans to file a biologics license application (BLA) with the FDA under the Public Health Service Act 351(a) regulatory pathway for biologics and innovator biologics in the first quarter of 2022. “If the BLA is approved, it is expected to result in 12 years of marketing exclusivity for ONS-5010 as the first and only ophthalmic formulation of bevacizumab approved by the FDA to treat wet AMD,” according to an Outlook 

. However, it would not be considered a biosimilar.

Off-label bevacizumab repackaged at compounding pharmacies is estimated by the National Eye Institute to account for roughly 50% of all wet AMD prescriptions in the United States.

The AAO has alleged that multiple payers are now recommending bevacizumab biosimilars as alternatives to Avastin for the treatment of ophthalmologic conditions.

In a statement, Horizon Blue Cross Blue Shield of New Jersey disputed its inclusion on the list. The payer said it 

 biosimilar use in ophthalmic settings and has been collaborative with physicians, contrary to the AAO's position. 

“Horizon works closely with New Jersey’s ophthalmologists and has formed collaborative relationships with many of the leading retina practices in New Jersey to jointly develop more effective protocols to treat wet AMD and diabetic retinopathy," Horizon told The Center for Biosimilars

. "These cooperative relationships are helping ophthalmologists deliver better quality care and improve the cost and experience for our members. Horizon’s policy concerning the use of an approved biosimilar for Avastin applies only to its use for patients who have certain cancers and who are new to treatment. As it relates to ophthalmic use for treatment of eye disease, the academy got it wrong—there is no policy requiring the use of a biosimilar for Avastin for any Horizon member.”

 it considers bevacizumab biosimilars to be viable treatments for multiple ophthalmic conditions and views more costly treatments, such as Eylea and Lucentis, to be “not medically necessary unless patients have a contraindication, intolerance, or ineffective response to the available equivalent alternative VEGF inhibitors: Avastin (or its biosimilars, Mvasi or Zirabev).”

Regardless of what payers are recommending, there are risks associated with use of compounded bevacizumab for ophthalmic conditions. Pfizer has published study data revealing somewhat higher risks for use of intravitreal bevacizumab vs ranibizumab. 

, updated June 17, 2021, indicates that Zirabev is not authorized for use in eye disorders and noted an observational database study of Avastin vs Lucentis that revealed an increased risk of intraocular inflammation for patients with wet AMD who received compounded bevacizumab vs authorized ranibizumab (HR, 1.82; 99% CI, 1.20-2.76) as well as a higher risk for cataract surgery (HR, 1.11; 99% CI, 1.01-1.23). The monograph also noted findings (from the same study) for increased risk of hemorrhagic stroke for patients who received intravitreal bevacizumab (HR, 1.57; 99% CI, 1.04-2.37).

for an interview with George Williams, MD, clinical spokesperson and past president of the AAO. 

Payers defend their policies on biosimilars in ophthalmic settings following allegations from the American Academy of Ophthalmology (AAO).


Payers Respond to AAO's Bevacizumab Biosimilar Contentions

When the FDA approves a biosimilar, it certifies that it is as safe and effective as the originator drug not just for the indication the biosimilar was approved for, but also for all other approved indications of the originator drug. But what about for off-label uses that the originator drug is used for?

This is a grey area where a battle is currently playing out in the field of ophthalmology. On one side is the American Academy of Ophthalmology (AAO), a group of 32,000 eye physicians and surgeons, and on the other are payers.

Through Medicare Advantage plans, payers have been encouraged to use step therapy, and when it comes to macular degeneration and other, potentially blinding diseases, many are treating bevacizumab biosimilars as equal to the bevacizumab reference product (Avastin).

The AAO contends this is putting the cart before the horse.

Based on extensive clinical studies, Avastin has been used for these eye conditions since 2005, but little-to-no clinical evidence exists for the use of bevacizumab biosimilars (Zirabev, Mvasi) for ophthalmologic treatment, and one product is produced using a substance that may be toxic to the retina, the 

For these reasons, the group is speaking out against payer policies that treat Zirabev and Mvasi as equivalent to Avastin in ocular medicine. The Center for Biosimilars

 (CfB) spoke with George Williams, MD, clinical spokesman for and past president of the AAO, about these concerns.

What follows is a partial text of Williams’ remarks. The full video interview will be published on Deep Dive, an MJH Life Sciences™ 

Editor’s note: Avastin helps control abnormal blood vessel growth and is FDA-approved in oncology. In ophthalmology, Avastin is not used in its original packaging form because the dosage requirements for intravitreal injection (eye injection) are very different. For this reason, Avastin is first sent to compounding pharmacies for conversion. It is currently the most-commonly-used compounded medication in ophthalmology.

Please could you give us an overview of the issue?

 We have a long clinical experience that's been validated by multiple national international clinical trials that demonstrate both the safety and efficacy of compounded Avastin in the management of a variety of ocular conditions, most prominently age-related macular degeneration, diabetic retinopathy, and retinal vascular occlusions. We have confidence based on those clinical trials and our cumulative experience in using compounded Avastin for over 15 years, across literally tens of millions of injections. Based on that experience, we know that compounded Avastin has a significant efficacy in these diseases.

We believe that the decision for therapy should be made between the patient and the physician, so we have this very unusual situation where payers are denying FDA-approved treatments and requiring patients to go through a "trial" with a non-FDA–approved [use] of a compounded FDA approved drug, and I believe that is without precedent.

CfB: Should it be concerning that the originator company, Genentech, has not sought an FDA decision for use of Avastin in ocular disease and there has been no FDA ruling on the safety and efficacy of Avastin for such conditions?

 The FDA hasn’t issued a ruling because they haven't been asked. Ideally, we would like to have a specific FDA approval process [for Avastin], but that’s unlikely to happen because Genentech has a similar product [ranibizumab, Lucentis] that they developed specifically for the eye that they believe has certain advantages over the compounded use of Avastin.

CfB: Could you elaborate on your concerns about the bevacizumab biosimilars?

 Neither of these products has been studied in the eye at any level. Before people tried using Avastin in the eye, there were preliminary animal studies and toxicology work to determine whether or not the eyes would tolerate it, utilizing accepted clinical models.

None of that has been done with the 2 available biosimilars. First, "do no harm." We need to establish that these drugs would be safe. Second, we have no evidence that they would be effective. There are no clinical reports that I’m aware of, and certainly no clinical trials, comparing these drugs with what we have available. I think it’s important to remember that we’re using these therapies for potentially blinding diseases, and so it’s incumbent upon physicians to be able to tell their patients that there are compelling data, both to the safety and to the efficacy of any treatment. We simply don’t have that in the biosimilar space. Additionally, we are bothered by the fact that both the companies Pfizer [Zirabev] and Amgen [Mvasi] have specifically stated that these products are not to be used in the eye.

"[Payers] are incorrectly assuming that biosimilars of bevacizumab are going to behave the same as Avastin in the eye, and they’re making that assumption with absolutely no data," contends George Williams, MD, clinical spokesperson and past president of the American Academy of Ophthalmology (AAO).