Cameron Santoro is an associate editor for The Center for Biosimilars

Cameron Santoro

Jeffrey Casberg

Jeffrey Casberg, MS, RPh, senior vice president of pharmacy at 

, discussed the FDA approvals of new drugs and what these new launches could mean for drug pricing. He also spoke to the approach pharmacy and therapeutics committees take to reviewing new pipeline drugs.

This transcript has been lightly edited for clarity. 

What is your reaction to the FDA approval of the first denosumab biosimilars?

So denosumab biosimilars, there was 2 approved; 

Wyost [denosumab-bbdz] and Jubbonti [GP2411]

. The Jubbonti is for Prolia, the Wyost is for Xgeva. One is more oncology based, one is more osteoporosis based.

They were approved, but there's no announcement on when they're going to be launched. We're thinking they might even be delayed in launch till 2025. 

With only one manufacturer coming out, Sandoz, with both of those, we'll get some discount on the brand and reference drug but it's not going to be significant. It's not going to be like the 

Humira [adalimumab] situation with 9 or 10 biosimilars.

What are your thoughts on what the launch of the first tocilizumab biosimilar means for patients with autoimmune conditions?

 is actually IV [intravenous] and sub-q [subcutaneous]. I think that the 2 products launched, 

 is both IV and sub-q, and that's from Fresenius Kabi.

For the most part, Actemra is used in rheumatoid arthritis, a couple other conditions as well. Getting biosimilars in a different therapeutic area, including Actemra, that will be a big advancement. That's 2 biosimilars, so we will get a little competition there on pricing, but I don't know if I can predict what the discounts will be—maybe, 20% to 30% off.

How are pharmacy and therapeutics committees likely to approach new pipeline drugs, considering factors like efficacy, safety data, and potential cost compared to existing options?

P&T [pharmacy and therapeutic] committees are pretty standard in their approach on how they review drugs for formulary inclusion. It really comes down to safety, cost, and efficacy.

I think in today's world, the only difference is that there's a lot of these new orphan drugs which don't have a lot of competitors, so the P&T committees have to look at a drug on its own or a small number of patients, so they really look at the efficacy opportunity—which patients should get the drug, and what the criteria can be.

It's a lot less managing 4 or 5 drugs in a therapeutic area and comparing the pros and cons of drugs that are very similar. Nowadays, we're comparing a million-dollar drug which has no competition and who the patient should be and what the criteria should be. So there is a little shift in reviewing drugs from multiple drugs in 1 therapeutic class to orphan drugs.

Videos

Jeffrey Casberg, MS, RPh, senior vice president of pharmacy at IPD Analytics, highlights new FDA approvals, the launch of the first tocilizumab biosimilar, and how pharmacy and therapeutics committees approach new pipeline drugs.

IPD Analytics' Jeffrey Casberg Discusses Recent Biosimilar Approvals

The Top 5 Biosimilar Articles for the Week of July 8

As the weather heats up for the US and Europe, so too did the 

, with clinical trial results from conferences and a study showcasing how to overcome economic and noneconomic barriers to oncology biosimilars.

 As Celltrion publishes phase 3 data on its tocilizumab biosimilar, other companies finalize partnerships, and Formycon 

 to receive approval for the American market. It was also approved with interchangeability.

FDA has approved Ahzantive (aflibercept-mrbb)

 as the third biosimilar referencing Eylea (aflibercept) for the treatment of eye conditions, including age-related macular degeneration.

 to remove switching study data for companies seeking to obtain an interchangeability designation for their biosimilars.

To read all of these articles and more, visit 

Here are the top 5 biosimilar articles for the week of July 8, 2024.

Recent data has utilized enhanced assessment of electronic patient-reported outcomes (ePROs) to identify undetected symptoms while improving symptom management for patients with various cancer subtypes. | Image Credit: Maksym - stock.adobe.com

Patients with HER2-positive breast cancer who were treated with biosimilar trastuzumab-dkst (Ogivri) experienced equivalent symptoms, adverse events (AEs), and well-being as patients treated with the originator trastuzumab (Herceptin), according to the results of a study published in 

Oncology care has benefitted significantly from biosimilars and their reference products, and these agents account for approximately 70% of the growth in costs of drugs from 2010 to 2015. Biosimilars are one way to reduce costs without affecting quality of care.

The study provided an enhanced assessment of electronic patient-reported outcomes (ePROs) that identified undetected symptoms while improving symptom management for patients with various cancer subtypes. The system has suggested improvements in well-being and awareness of AEs between outpatient visits.

The ePRO application collects patient-reported information in clinical trials, including symptoms, quality of life, treatment adherence, and treatment satisfaction. Data is accurately reported in real time and offers informed decisions when analyzing the efficacy and safety of medical interventions. The technological application allows patients to report their treatment results without the limitations of paper-based methods, with valuable insights delivered more efficiently and accurately.

There is limited research on the real-world outcomes, tolerability, and quality of life that has been performed using ePRO data collected from patients treated with anti-HER2 biosimilars.

An observational study was conducted to investigate the daily functional activity, symptoms, and therapy AEs recorded with medidux smartphone application in patients undergoing trastuzumab-dkst therapy.

In December 2017, trastuzumab-dkst was approved by the FDA as the first trastuzumab biosimilar for treatment of HER2-overexpressing breast or metastatic stomach cancer.

 Some patients experienced AEs such as fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, shortness of breath, rash, low white and red blood cell counts, and muscle pain.

Over a 20-month duration, a noninterventional, multicenter, prospective, observational study was held across 5 study sites in Switzerland.

The study enrolled patients who received an anti-HER2 treatment regimen. This regimen included an initial intravenous dose of trastuzumab-dkst at 8 mg/kg body weight, followed by maintenance doses of 6 mg/kg. The treatment could be given with or without pertuzumab, chemotherapy, and/or hormone therapy, depending on whether it was administered in a neoadjuvant (pre-surgery) or palliative (symptom management) setting.

The medidux app is a patient-centered, therapy assistance application that supports the structured, standardized, and dynamic documentation of symptoms and therapy AEs. Patients received the app and were instructed to record their symptoms, well-being, EQ-5D-5L questionnaires, cognitive capabilities, and vital parameters every day. Regular study visits were scheduled on days 1, 21, and 42 during 3 weekly chemotherapeutic interventions.

Each patient had an observational period that lasted 6 weeks and at the end, patients decided whether to continue therapy with trastuzumab-dkst or the originator trastuzumab.

The study had a primary objective to evaluate ePRO data received in the medidux app by patients with HER2-positive breast cancer treated with trastuzumab-dkst while comparing the data with ePRO findings obtained from a historical cohort treated with trastuzumab in 2 previous studies (

The well-being of patients in both cohorts and the electronically reported symptoms was considered the secondary objective.

A total of 53 patients who identify as female were enrolled in the study with an average age of 57 years in the prospective cohort and 51 in the historical cohort. Around 38.9% of patients had tumor stage 2 with fewer patients (22.2%) had palliative treatment than neoadjuvant or adjuvant treatment. Over half of the population received dual anti-HER2 blockade with trastuzumab and pertuzumab (59.3%).

Patients in the prospective cohort experienced 84 of the 92 available different symptoms entered in the app, with the average being more than 4 symptoms a day, that resulted in a total of 9680 symptoms.

There were 54 of the 82 different symptoms found in the historical cohort, with the average being more than 3 symptoms a day, that resulted in 6904 symptom entries.

Common symptoms included fatigue, taste disorder, nausea, diarrhea, dry mucosa, joint discomfort, tingling, sleep disorder, headache, and appetite loss. Most patients in the trastuzumab-dkst cohort experienced minimal (grade 0) and mild (grade 1) toxicities, followed by grade 2, 3, and 4 toxicities.

Common Terminology Criteria for Adverse Events (CTCAE) Score

The primary end point was evaluated among 50 patients who received trastuzumab-dkst and 38 patients treated with the originator trastuzumab.

The average CTCAE scores could be compared between the 2 cohorts with an estimated difference of –1.27 (95% CI, –7.24 to 4.70; 

 = .68). Notably, the adjusted average of CTCAE scores were not altered between cohorts either (2.51; 95% CI, –3.27 to 8.29).

Secondary end points were analyzed in 52 patients who received trastuzumab-dkst and 38 patients as part of the historical cohort. On average, the difference in well-being patients treated with trastuzumab-dkst and originator trastuzumab was 4.45 (95% CI, –3.53 to 12.44; 

 = .28). There were no major differences between the adjusted well-being scores (3.78; 95% CI, –4.64 to 12.19) of both groups.

Cognitive Abilities in the Prospective Cohort

Data from 37 patients (70%) who performed at least 1 cognitive test were involved in the analysis, with 767 cognitive tests entered overall. The average execution time was 42.9 seconds. However, the small sample size and limited number of cognitive tests recorded were not correlated to the cognitive abilities and treatment performed.

The study design limited the results because it neglected a prospective control group and could not be randomized. Additionally, the app was not skilled to perform questionnaires to patients and cognitive abilities were not available for the historical cohort.

Future studies are necessary to analyze data through a randomized design with real-world functions in patients with HER2-positive breast cancer who were treated with anti-HER2 biosimilars.

Ultimately, treatments of both trastuzumab-dkst and the originator expressed equal symptoms, AEs, and well-being as reported by ePRO. Results highlighted the integration of an ePRO tool into research and clinical practice can provide reliable information when investigating tolerability and safety outcomes of similar therapeutic compounds.

1. Trojan A, Roth S, Atassi Z, et al. Comparison of the real-world reporting of symptoms and well-being for the HER2-directed trastuzumab biosimilar ogivri with registry data for herceptin in the treatment of breast cancer: Prospective observational study (OGIPRO) of electronic patient-reported outcomes. 

2. The ultimate guide to ePRO: Everything you need to know. Lindus Health. Accessed July 1, 2024. 

https://www.lindushealth.com/blog/the-ultimate-guide-to-epro#:~:text=Defining%20ePRO%3A%20What%20It%20Is%20and%20Its%20Importance&text=In%20simple%20terms%2C%20ePRO%20involves

3. FDA approves Ogivri as a biosimilar to Herceptin. News release. FDA. December 1, 2017. Accessed July 2, 2024. 

https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ogivri-biosimilar-herceptin#:~:text=On%20December%201%2C%202017%2C%20the,gastric%20or%20gastroesophageal%20junction%20adenocarcinoma).

4. OGIVRI (trastuzumab-dkst). Ogivri. Accessed July 2, 2024. 

Articles

Patients with HER2-positive breast cancer treated with the biosimilar trastuzumab-dkst experienced similar adverse events and well-being as those treated with the originator drug (Herceptin), according to a study using a smartphone app to track symptoms.

Trastuzumab-dkst Matches Herceptin's Safety, Well-Being for HER2-Positive Breast Cancer

Here are the top 5 biosimilar articles for the week of July 1, 2024. 

The Top 5 Biosimilar Articles for the Week of July 1

 for the treatment of inflammatory conditions, including plaque psoriasis and ulcerative colitis.

, 1 in Crohn disease (CD), and 1 in ulcerative colitis (UC), found 

 in patients treated with the subcutaneous formulation of infliximab biosimilar CT-P13 (Remsima, Inflectra; Celltrion) compared with placebo as maintenance therapy following an induction phase of intravenous CT-P13.

Key findings showed that there continues to be a lack of understanding and/or confidence in biosimilars 

, leading to diminished provider willingness to prescribe biosimilars and patient perceptions about the safety of switching to a biosimilar.

Here are the top 5 biosimilar articles for the week of July 1, 2024.

Jeffrey Casberg Q3

Jeffrey Casberg, RPh, MS, senior vice president of pharmacy at 

, considers the top 3 promising biosimilars currently coming down the pipeline. He addresses the significance  of each and the specific areas of health they treat.

He also touches on the FDA Advisory Committee and speaks about the obstacles that have delayed approvals for these medications.

This transcript has been lightly edited for clarity.

In your view, what are the top 3 promising specialty drugs currently coming down the pipeline and why should stakeholders be keeping an eye on them?

The first one I'll talk about is donanemab for Alzheimer's disease by 

; it's an amyloid-β inhibitor for early Alzheimer's disease. It would be a little bit different than 

 from Biogen, which was fully approved more recently.

Donanemab was originally going to be approved beginning of 2023, so over a year ago, but it has had a little bit of a storied pathway to approval. We were watching for an approval here any day during this last month or so, then out of the blue, there was an announcement that the FDA has requested an 

If I'm a manufacturer, not really happy about that; you never really want extra scrutiny on your drug. I'm sure they're going to talk about the dosing regimen, the potential for shorter duration of therapy compared to Leqembi probably the ARIA [amyloid-related imaging abnormalities] side effect profile. They haven't given us a date for that FDA Advisory Committee meeting. I would anticipate a date being announced any day and I still think there's opportunity for approval before the end of 2024.

I think one of the other products that is exciting is resmetirom, or Rezdiffra. for NASH [nonalcoholic steatohepatitis]. First product approved for NASH. Again, a therapeutic area we've been waiting for therapies now for maybe 10 years. Finally we do have an approval. Congratulations to 

 on that, getting their product over the finish line.

A once daily, oral product. It showed signs of efficacy and NASH resolution and fibrosis improvement. Prescribing information did not include discussion of the need for biopsy in diagnosis. So, to diagnose NASH, now called MASH [metabolic dysfunction-associated steatohepatitis], the gold standard is liver biopsy, but that's pretty invasive. You can also use noninvasive therapy testing to get diagnosis of staging of NASH in the liver. They did not have that, which was a plus for Madrigal.

It would be interesting to see how the payers set up their criteria for approval. There's a whole lot of population out there that could be treated with this, so that's another big approval that just occurred. 

I'll just mention one other recent approval. It's called 

 for pulmonary arterial hypertension, sotatercept, by Merck. Winrevair is the brand name.

It's a new product for PAH, pulmonary arterial hypertension. It's a new mechanism of action, and has the potential to be more disease modifying—the other therapies out there are more symptomatic treatments—and probably early on will be used as add-on or [in the] second or third line. But I think as physicians get used to it, they could move it up in therapy.

It is pretty expensive: $240,000 for most patients, could be $480,000 for some patients. It's a weight-based dosing, so 1 vial or 2 vials. I think it's subcutaneous every 3 weeks, and it can be self-administered or professionally administered.

In an interview with Jeffrey Casberg, MS, RPh, he discusses 3 promising specialty drugs coming through the pipeline. Casberg explains these drugs offer new treatment options for major diseases and stakeholders should watch for their potential impact on the market.

Jeffrey Casberg of IPD Analytics Gives Insight on Specialty Drugs in the Pipeline

Here are the top 5 biosimilar articles for the week of June 24, 2024. 

British Columbia's Biosimilars Initiative

 successfully saved about $732 million over 5 years by switching over 40,000 patients from reference biologics to biosimilars, while maintaining equivalent health outcomes and reinvesting the savings into the province's public payer program (BC PharmaCare) to enhance drug coverage and health care services.

 Sarfaraz K. Niazi, PhD, makes suggestions for what arguments will help 

convince the FDA to waive clinical efficacy testing requirements

 has the potential to significantly reduce cancer care costs and improve patient access to more affordable treatments, benefiting both patients and payers. However, a recent review highlights that biosimilar uptake has been hindered by various economic, practical, attitudinal, and psychological factors.

 of this series installment by The Center for Biosimilars®, the role of payers, pharmacy benefit managers (PBMs), and the financial incentives that influence prescription choices are addressed as obstacles towards affordable biosimilar treatments, specifically among underserved communities.

 to its guidance on requiring switching study data for biosimilars to be granted interchangeability, citing new science that shows these studies aren’t needed to establish biosimilar safety.

Here are the top 5 biosimilar articles for the week of June 24, 2024.

The Top 5 Biosimilar Articles for the Week of June 24

IDP Analytics SVP Says IRA, PBM Legislature Reshape US Drug Costs

In an interview with Jeffrey Casberg, RPh, MS, senior vice president of pharmacy at 

, discussed policy changes and market forces that are impacting the cost of drugs. Casberg explained why he felt the Inflation Reduction Act (IRA) and pharmacy benefit manager (PBM) legislation are the most impactful.

He also touched on value-based pricing models. Although skeptical of value-based pricing being a universal solution, Casberg sees promise in its use for expensive drugs, like gene therapies, where outcomes can be more easily measured.

Do you foresee any policy changes or market forces that could significantly alter the cost landscape for both branded and generic drugs in the near future?

So policy or legislation, everything is about politics. I guess I'll mention 2 things. I'll mention the 

. Those would be the 2 hot ones on the IRA side, we just had the first release of the negotiated drugs and which drugs they are. We'll be getting 

, a new acronym for drug pricing, those will be announced coming up soon.

We're going to have the out-of-pocket cost of Part D reduced to the max of an out-of-pocket cost to $2,000. That's big for patients, impactful to manufacturers, and payers. Now they're going to have to deal with different benefit designs and how they're going to market the drug and price the drug or how payers are going to make the benefits work with the new $2,000 max, so there is something for everybody there.

Then 2025 redesign, for the Inflation Reduction Act, there's also quite a few different benefit designs changing for 2025. There's 

 so the manufacturers have to watch how much they're raising the prices of their drugs. If they go up too high, too quickly, then they get these penalties against them. The IRA has a number of different things, pretty complex, and everybody's paying attention to that.

Then on the second hand, it would be PBM legislation. I guess it depends on who you are and your feeling towards PBM legislation. I think it probably just comes down to more transparency. Every business has to make money and PBMs have done it. Somebody could argue they did it okay. Some say it was all smoke and mirrors but I think there's legislation now to have more transparency on PBMs. We'll see how that rolls out but a lot of discussion up in Washington on that these days.

Value-based pricing models are increasingly being explored. How do you think value-based pricing will impact the development, approval, and access to new drugs?

So value-based pricing, you hear a lot about it. You hear people trying to implement it, manufacturers bring proposals to payers on value-based pricing models. What we don't hear of are the results and if they are working or not.

I don't know in the long run, if value-based pricing will be the 'be all and end all' and change the way drugs are paid for in the United States. I'm going to say no but I think there's some value to value-based pricing and in how you look at drugs and evaluate them.

I think especially some of these high cost therapies have opportunities for some value-based models. As I was saying earlier, there's more and more of these high cost, really expensive products and looking at outcomes and measuring outcomes, that kind of thing are for these gene therapies and other expensive therapies.

I'm not saying value-based pricing will take over but I think there's opportunity in the future for use of them.

Jeffrey Casberg, RPh, MS, from IPD Analytics, explains why he believes policy changes and market forces are impacting the cost of drugs, including the Inflation Reduction Act (IRA) and pharmacy benefit manager (PBM) legislation.

IPD Analytics' Jeffrey Casberg Says IRA, PBM Legislation Reshape US Drug Costs

The Top 5 Biosimilar Articles for the Week of June 17

 A real-world study of children and young adults with inflammatory bowel disease (IBD) switched from the infliximab reference product to a biosimilar concluded 

 over 12 months based on stable remission rates and biochemical markers.

 with non-infectious uveitis from originator adalimumab to biosimilar adalimumab-atto was safe and effective, but some patients experienced the nocebo effect, where negative adverse events are caused by patients’ poor perception of the drug rather than the medication itself.

European Hematology Association’s (EHA) 2024

 annual meeting in Madrid, Spain, showed similar rates of transfusion avoidance between patients with paroxysmal nocturnal hemoglobinuria who were administered reference eculizumab (Soliris) and those administered an eculizumab biosimilar (SB12).

 British Columbia's 2019 Biosimilars Initiative, which transitioned over 40,000 patients from costly branded biologics to biosimilars, saved around 

, maintained comparable health outcomes, and reinvested the savings to improve the province's public payer program.

 Sarfaraz K. Niazi, PhD, makes suggestions for what arguments will help convince the FDA to waive 

Here are the top 5 biosimilar articles for the week of June 17, 2024.

Health Equity Chart | Image Credit: leowolfert - stock.adobe.com

In the second and final part of this series installment by The Center for Biosimilars

, the role of payers, pharmacy benefit managers (PBMs), and the financial incentives that influence prescription choices are addressed as obstacles towards affordable biosimilar treatments, specifically among underserved communities.

Part 1: Unlocking the Potential of Biosimilars to Improve Health Equity

”, highlighted the medical mistrust that underserved communities have towards health care systems and professionals. Solutions to this issue included further education among patients and physicians to attempt to close knowledge gaps while gaining trust from patients.

Part 2 shifts focus onto the professional health care systems that may be imposing boundaries towards biosimilar access through a financial lens. We will continue to investigate why biosimilars are not achieving the market adoption they deserve.

Biosimilars have the potential to increase patient access to life-saving medications at lower costs but barriers from pharmacy, physician, and insurance groups limit patient access to health equity, especially for underserved communities.

Pharmacies, Physicians, and Insurance Groups

Biosimilar barriers, often perpetrated by insurance companies, affect pharmacies and physicians as well pharmacy benefit managers, health care providers, and policymakers. Prescription drug insurance benefits are usually negotiated by managed care organizations (MCOs), integrated delivery networks, and PBMs. Research found both medical and pharmacy benefits were usually managed by MCOs or PBMs (91.7%). These high-level roles offer physician practices and institutions financial incentives, awarded to them when more expensive originator biologics are prescribed over biosimilars.

In order to understand the limited uptake of biosimilars, the 340B Drug Pricing Program must be addressed. In 1992, Congress introduced the 340B Drug Pricing Program, allowing pharmaceutical manufacturers participating in Medicare and Medicaid Part B programs to begin a contract relationship with the Secretary of Health and Human Services.

 The program requires participants to apply discounts on covered outpatient drugs when purchased by specific covered entities. Covered entities include some disproportionate share hospitals, children’s hospitals, rural hospitals, critical access hospitals, rural referral centers, sole community hospitals, and free-standing cancer hospitals. However, the 340B program has quickly turned into disadvantages for patients and manufacturers, leaving insurance companies reaping all the benefits.

Under Medicare Part B programs, drug costs are unevenly allocated among doctors and 340B participating hospitals. Where doctors typically see a 16% profit margin and hospitals make an average of 140% profit, 340B hospitals make around 210% of a profit.

 This furthers the notion that profit margins seem to be a greater focus than people in these health care systems. Commercial insurance contracts and steep discounts are likely to blame for these significant differences in profit. These policies are standing in the way of patient cost savings, allowing providers to profit from contract rebates that favor more expensive products while preventing savings from being directly passed down to patients.

Pie graph representing profit margins of doctors, hospitals, and 340B hospitals. Source: American Hospital Association

Payer-created prior authorization requirements also affect the timely treatment that could be offered to patients. As a result, patients may not feel biosimilars are worth it if they must depend on slow moving prior authorizations. As patients wait days or weeks for approval, their condition could exacerbate.

The lack of biosimilar knowledge or education among physicians does not help with uptake among patients either. Countless survey studies found evidence that physician and patient knowledge of biosimilars is insufficient, likely because they are not entirely familiar with the biosimilar regulatory approval process.

 While innovator biologics rely on clinical data to establish safety and efficacy of the innovator product, the development of biosimilars has limited reliance when compared with the biosimilar and innovator. The oncology space is likely being impacted by these concerns since recently approved cancer treatment biosimilars are not receiving adoption as fast as supportive care biosimilars have.

Additionally, biosimilar development includes the idea of extrapolation of indications, where studies utilize a patient population more sensitive to attempt to find clinically meaningful differences between the originator and biosimilar products. This allows comparative clinical studies to be waived for each indication approved for the innovator product. Many oncologists and gastroenterologists have expressed concerns over the extrapolation of indications, as well as clinicians across medical specialties.

Overall, strict mandates remove patient choice and can leave them focused on negative assumptions about biosimilars that could amplify or misattribute symptoms. These restrictions must be further researched to identify PBM price negotiations that result in patient access to expensive biologic treatment therapies.

Common obstacles patients and physicians face when attempting to achieve health equity through biosimilar access. 

Payers and PBM policies that favor more expensive reference products affect the accessibility and affordability of biosimilars, blocking biosimilars from being able to help achieve health equity. To address these systemic issues, all stakeholders will need to take action to help ensure access to biosimilar treatments.

Robert Popovian, PharmD, MS, a health economist and founder of Conquest Advisors, said in an interview with The Center for Biosimilars regarding current solutions, “We have done some policy work to shape the [biosimilar] environment but it's not enough. As you see, there's a significant struggle that the Humira biosimilars are having with regards to market penetration.”

When adalimumab (Humira) biosimilars hit the market in 2023, the assumption was competition among various similar biologic drugs would drive down prices.

 For some companies, this has been the case after choosing a dual-pricing strategy that launched the adalimumab biosimilars at 2 wholesale acquisition costs (WACs) or those that launched both branded and unbranded biosimilars at different price points.

 The idea was to ensure companies could convince PBMs to add their products on formularies (high WAC) while allowing patients without insurance to access the product at an affordable price (low WAC).

However, adalimumab biosimilars and the reference product do not guarantee cheaper costs. While some adalimumab biosimilars have steep discounts from the current price of the reference product, they are often more expensive than the originator. When the drug cost is more expensive for patients, PBMs receive a larger profit because they are awarded a portion of the drug’s list price.

A lot of adalimumab biosimilars are priced significantly lower than Humira, and some companies have launched their biosimilars with 2 wholesale acquisition costs. However, if payers and PBMs aren't willing to add these medications to formularies, the savings won't get passed to the patients. 

Pharmacy benefit managers need to be more transparent about their role, negotiation processes, and disclosure of rebate retentions to build trust from stakeholders, health care providers, and policymakers. 

The “big 3” PBMs (Express Scripts, OptumRx, and CVS Caremark) all have adalimumab biosimilars listed on the high-list price formularies.

 Market penetration can take years to show effective results so the issue surrounding adalimumab biosimilars should be addressed as soon as possible to ensure cost effectiveness later down the line and promote health equity. Samsung Bioepis reported a 53% market share after the first 3 years of the initial launch of an adalimumab biosimilar but found uptake speed differed overall among treatment spaces.

Across other companies, the uptake of biosimilars over the past 3 years ranged from 8% for drugs like insulin lispro to 82% for bevacizumab.

Near the end of 2023, adalimumab biosimilars reached only 2% of market volume. It is possible the reason for low adoption rates is based on the contracts the originators have with insurers, as well as the formulary differences of the citrate-free high potency form of the originator.

Step therapy, also known as health plan-imposed coverage exclusions, play a role in restricting access to biosimilars for patients in need. Ironically, biologics generate an average of $120 billion in drug net spending and 93% of the overall growth in total drug spending for 10 years. However, biologics account for only 2% of all patient prescriptions.

In a database analysis, 19.4% of biosimilars were restrictedly covered compared with their reference products.

 The study focused on a total of 17 health plans and found 6 plans had step therapy restrictions on biosimilars for less than 10% of all coverage decisions and 5 plans restricted biosimilars for more than 30% of all coverage decisions offered. Results found more restrictions on biosimilars if they were for diseases that had prevalence greater than 1,000,000 patients in the US. However, less restrictions were placed on biosimilars that could generate savings greater than $15,000.

The idea of penetrating health care providers with policy changes may seem impossible. However, in some instances, it has already been done and shown success. Kaiser Permanente, a large-scale insurer, has removed what most experts find to be a major issue in biosimilar uptake, known as rebate contracting.

Popovian commented, “Kaiser Permanente has made it possible to negotiate with pharmaceutical companies without using rebate contracting, proving it is possible. The insurer can gain all the savings upfront and pass it on to patients from an out-of-pocket cost perspective without using a PBM to negotiate contracts.”

The only downside to this solution is the decision to remove contract rebates lies in the hands of PBMs, which are unlikely to go along with these changes.

To combat this issue, Popovian suggested to, “delink the fees from the price of the medicine, that means to create a flat fee for any kind of services that the PBM may provide.” Another possible solution surrounds addressing benefit design for biopharmaceuticals, leaving patients unaware of the drug costs in generics and brands because it is a flat rate.

Fortunately, legislature is arising as a possible solution, suggesting portions of rebate savings to be passed through payers or patients in favor of underserved communities.

Ha Kung Wong, JD, an intellectual property attorney and partner at Venable LLP, spoke to The Center for Biosimilars on government policy, stating “[Congress] could eliminate the separate categories of biosimilar and interchangeable [products] to eliminate confusion for patients and prescribers and to allow for automatic substitution at the pharmacy level.”

Wong goes on to explain how effective this process was in Europe and how it could potentially “provide better awareness and better avenues for biosimilars to be listed higher up in insurance formularies such that patients will have access to better coverage for biosimilars.”

These examples provide evidence that policies surrounding biosimilars in the health care space can and should be changed to unlock their full potential.

In an interview, Chiara Gasteiger, PhD, of Stanford University’s Mind and Body Lab researching as a postdoctoral scholar, suggested that to combat trust issues among patients, providers, and physicians “there needs to be more transparency on the role of PBMs, their negotiation processes and disclosure of rebate retentions to build trust and understanding from stakeholders, health care providers and policymakers. Existing regulations should also ensure that PBMs comply with laws that protect patients and encourage fair pricing.”

Aside from financial and political challenges, biosimilar education remains a barrier to uptake. With some health care providers still not confident in their knowledge about biosimilars, patients are less likely to have access to these medications. Without access, biosimilars can’t aid in the fight to achieve health equity.

“More education, such as on testing and manufacturing, needs to be integrated into medical training curriculums and all providers should have access to comprehensive training programs that are regularly updated with new designations, guidelines, and policies,” Gasteiger suggested.

In addition, the introduction of electronic health records allows real time data to be exchanged among health care teams, payers, and providers because prior authorization requirements often influence timely treatment among patients. Gasteiger stressed the importance of these groups attempting to collaborate to share resources, improve ongoing communication about prior authorization, and streamline processes. The reduction of administrative complexities to be less frequent and expedited can assist with further uptake and adoption. 

Profit exceeds the amount of biosimilars prescribed. 

Insurers pose threats towards biosimilar accessibility, often for their own financial benefit, while physicians and pharmacies struggle with the limited power they hold. It is up to all health care stakeholders to work together to create a more accessible health care system and participate in frequent discussions where concerns can be addressed in a supportive environment with evidence-based policies.

Gasteiger commented, “Encouraging more research and providing research grants that enable providers to share experiences with interchangeability may also provide reassurance for some prescribers and help build trust. Research may also help professional medical organizations and other relevant organizations develop consensus statements.”

Low patient awareness and unfavorable perceptions of biosimilars stem from their physicians’ and pharmacies’ lack of awareness. Aside from overall unfamiliarity of biosimilars, providers have the power to transfer their negative expectations to patients. A study found less than 50% of the survey polled patients had heard of biosimilars and among them, 50% worried about the biosimilar being less effective than the innovator and 46% expressed concerns about the biosimilar safety profile.

A multi-pronged approach that tackles financial incentives, education, and communication is necessary to dismantle these barriers and unlock the full potential of biosimilars for improved patient access and affordability.

Despite offering substantial cost savings and improved access to treatment, particularly for underserved communities, biosimilars face hurdles within the healthcare system. Addressing these challenges through policy changes, increased education for both patients and providers, and improved communication among all stakeholders is essential to unlocking the full potential of biosimilars and expanding access to affordable treatment.

 Evolving perceptions, utilization, and real-world implementation experiences of oncology monoclonal antibody biosimilars in the USA: Perspectives from both payers and physicians. 

2. Krishnamurthy B, Kuhlman A. New error-ridden 340B study misses the mark. American Hospital Association. www.aha.org. February 7, 2024. Accessed June 3, 2024. 

https://www.aha.org/news/blog/2024-02-07-new-error-ridden-340b-study-misses-mark#:~:text=They%20examine%20the%20difference%20between

3. Boccia R, Jacobs I, Popovian R, de Lima Lopes G Jr. Can biosimilars help achieve the goals of US health care reform?. 

4. Shubow S, Sun Q, Nguyen Phan AL, et al. Prescriber perspectives on biosimilar adoption and potential role of clinical pharmacology: a workshop summary. 

5. Yu T, Jin S, Li C, Chambers JD, Hlavka JP. Factors associated with biosimilar exclusions and step therapy restrictions among US commercial health plans. 

6. Dashevsky J. The rise of Humira biosimilars and the battle for market share. Healthcare Huddle. January 28, 2024. Accessed June 3, 2024. 

Part 2 of this series dives into the health care system, revealing financial hurdles that limit biosimilar access and ultimately hinder health equity.