Upon admission to hospital, patients who had been taking insulin degludec (iDeg) at home may receive inappropriate dosing when switched to another insulin, and this is because physicians tend to have a poor understanding of the pharmacodynamics (PD) and pharmacokinetics (PK) of iDeg, investigators concluded in a study presented at the American Diabetes Association 80th Scientific Sessions online conference.

Lead investigator Jing H Chao, MD, and Irl B. Hirsch, MD, observed widely variable practice in transitioning patients from iDeg to insulin glargine U100 (iG100) upon admission, but for various reasons, patients with type 1 diabetes were found to be at much higher risk of developing hypo- and hyperglycemia than patients with type 2 diabetes.

A key reason for the complexity of transitioning patients from iDeg to iG100 is that iDeg has a half life of 25 hours, more than twice that of iG100, meaning it remains in the body at higher concentrations for longer, up to 42 hours versus 24 for iG100, Chao explained. Hospital-based physicians may not understand this and give patients too much or too little iG100 to maintain insulin levels following home dosing. “Physicians should judiciously determine the amount of insulin to be given,” Chao said.

Part of the reason for the knowledge deficiency may be that iDeg, a Novo Nordisk product, was FDA approved just 5 years ago. An advantage of IDeg is that it enables physicians to achieve a more stable background level of insulin in the body relative to insulin glargine, which “waxes and wanes,” Chao said.

So, when switching to iG100 upon admission, it is important to take into account the different rate at which iDeg is excreted from the body. “By the 24th hour, there is still 50% of the background degludec on board. By contrast, when you have glargine, most of the glargine has already been washed out,” Chao said. “If patients were to receive a 100% glargine dose at the 24-hour mark, that would raise their basal [or background] insulin to 150% of the basal insulin that’s on board at that point.”

In the study, Chao and Hirsch noted that clinicians gave iG100 at 0% to 100% of the home-based iDeg dose anytime between 24 hours and 72 hours after the last iDeg dose, “demonstrating a general lack of understanding of the PK and PD of iDeg and a great need to standardize this transition.”

“Physicians are giving 100% of the glargine at the 24th hour, leading to over-basalization of the insulin,” she said.  Excessive insulin can lead to hypoglycemia and, consequently, altered mental status and potential cardiovascular events, including heart attack.

“Not only do physicians vary the time at which they give the first dose of glargine, they also vary the amount of the glargine they give as compared to the home dose. That part was not surprising to us,” Chao said.

“What is surprising to us is that despite such variable practice, we did not see hypoglycemia in patients with type 2 diabetes, and the reason is that compared with type 1 diabetes, patients with type 2 diabetes have a better buffer in that they continue to secrete a small amount of insulin and continue to secrete some glucagon. These are countering hormones that buffer them and help prevent them from getting hypoglycemia as much as patients with type 1 diabetes,” she said.

Mild hypoglycemia was observed in 2 patients with type 1 diabetes, or 28.6%. there were no cases of hypoglycemia in the type 2 group (n = 32).

Another factor to consider is that patients when admitted tend to be under higher levels of physiologic stress, which causes them to require increased amounts of insulin. So, the tendency on the part of physicians to provide too much iG100 is counterbalanced by the body’s need at this point for more insulin than usual, Chao said. “For these reasons we don’t see hypoglycemia in patients with type 2 diabetes.”

“We found that, to counter the amount of stress-induced hyperglycemia, when patient receives 50% to 75% of the glargine at the 24-hour mark, which leads to total of 100% to 125% background basal insulin level at that time, their blood sugar is actually better controlled,” she said.

“If you give anything up to 49%, that gives them less than their home dose, and is insufficient to cover their basal insulin requirement during a stressful hospitalization.”

Chao and Hirsch are hoping that their study prompts physicians to think more carefully about the PD and PK of iDeg and carefully assess other factors when determining follow-up dosing, such as meals taken, stress from hospitalization, renal function, and whether patients were on a sufficient home dose of insulin to begin with. Renal considerations are key with iDec, because it is not excreted via the kidneys.

The investigators also would like to see further studies conducted, leading to the development of guidelines.

“We’re hoping that prospective trials can be conducted to take a better look at the transition to determine the recommendations on how much insulin glargine to give at what point of their patients’ hospitalization that will ensure patients safety during this complicated transition,” Chao said.

For more about insulin degludec, see these stories about 

Chao JH, Hirsch IB. degludec-to-glargine transition: the first real-world study. Poster presented at: American Diabetes Association 80th Scientific Sessions; June 12-16, 2020. Poster 1025-P.

Articles

There is much inconsistency in the way physicians transition patients from insulin degludec to insulin glargine upon hospital admission, leading to higher risk especially for patients with type 1 diabetes, according to a study presented at the American Diabetes Association 80th Scientific Sessions online conference.
 

Doctors Manage Insulin Degludec-to-Glargine Transition Poorly, ADA Study Says

Hi, I’m Skylar Jeremias for The Center for Biosimilars®, your resource for clinical, regulatory, business, and policy news in the rapidly changing world of biosimilars.

The European Hematology Association recently held its 25th Annual Congress, EHA25 Virtual, from June 11 through June 21. The meeting was conducted on a digital platform due to the coronavirus disease 2019 (COVID-19) pandemic and featured some key study findings and presentations on the up-and-coming world of hematology biosimilars.

The following is a summary of our biosimilar coverage from this event:

Investigators produced what they described as the 

 the use of biosimilar erythropoiesis-stimulating agents (ESAs) in patients with myelofibrosis (MF)-related anemia.

Investigators said ESAs are used to manage anemia in hematological malignancies, but scarce evidence exists for the use of these agents in the treatment of MF, and available results are divergent: Response rates range from 23% to 69%, according to the abstract presented at EHA25 Virtual. Until this study, there were no data on the use of biosimilar ESAs in this setting, investigators said.

Investigators reported an 88% overall response rate for a Sandoz rituximab biosimilar in combination with chemotherapy in patients with CD20-positive diffuse large B-cell lymphoma. At the end of treatment, the complete response was 57% and partial response was 31%. Investigators said 61% and 29% of patients experienced enlarged lymph nodes and disease-related pain, respectively.

 presented this month at EHA25 Virtual confirmed findings from the REFLECT study released in 2019, which was the first prospective postapproval study to evaluate a rituximab biosimilar in this context.

 that a rituximab biosimilar developed by Celltrion Healthcare (Truxima) in combination with lenalidomide and acalabrutinib (R2A) in patients with relapsed or refractory aggressive B-cell lymphoma was tolerable and effective.

The addition of rituximab, a targeted therapy, to chemotherapy agents can improve patient outcomes but adds to the financial burden of treatment. Investigators said that exploring the use of biosimilar rituximab may be an avenue to bring down costs.

To read all of these articles, visit our EHA 

Videos

Here is a summary of our coverage from EHA25 Virtual, the annual meeting for the European Hematology Association (EHA).

EHA25 Virtual Roundup

Although adalimumab and etanercept biosimilars have been approved in the United States, these have not yet been brought to market, owing to exclusivity 

. However, European studies investigating real-world applications of these agents are well along, based on presentations at the EULAR 2020 Congress, the virtual meeting of the European League Against Rheumatism.

An Italian study at Padova University Hospital evaluated the rate of switching from originator versions of these drugs to biosimilars in patients with rheumatoid arthritis (RA), psoriatic arthritis (PSA), and axial spondyloarthritis (axSpA). Investigators also evaluated survival for patients who switched to biosimilars versus those who didn’t.

The study enrolled 1208 patients, of whom 560 (46.3%) switched to biosimilars: etanercept (n = 391) or biosimilar adalimumab (n = 169). The mean disease duration was 16 years, and the mean duration of the biologic disease-modifying antirheumatic drug (bDMARD) was 96.3 months.

Investigators said factors associated with switching were longer disease duration, shorter duration of previous bDMARD treatments, and diagnosis. Patients with RA had an almost 3-fold higher likelihood of being switched to biosmilars compared with patients with PSA or axSPA, according to the study. Investigators said the difference between PSA and axSPA in this context was not significant.

A longer drug survival was observed in patients who switched versus those who continued with originator drugs (HR 1.38; 95% CI, 1.2-1.58); however, investigators concluded that switching from the reference biologic to the biosimilar “does not affect the survival of the treatment. Indeed, it provides sustained effectiveness particularly if undertaken in patients with stable disease activity.”

They said longer drug survival was associated with longer disease duration, longer mean duration of previous bDMARDs, and diagnosis.

Investigators also concluded that “patients with longer disease duration and longer bDMARD duration were most likely to be switched successfully to biosimilars.”

In a second switching study, also conducted in Italy, investigators sought to evaluate the safety and retention rate for patients switched from the originator etanercept to the biosimilar (SB4, Benepali).

The study enrolled 220 patients with RA, PSA, and ankylosing spondylitis (AS), juvenile idiopathic arthritis (JIA), and other rheumatic diseases treated with originator etanercept for at least 6 months. Investigators collected data on adverse events, loss of efficacy, and persistence on treatment. The rate of retention, reason for discontinuation, and other management data were collected at 6, 12, and 18 months.

Investigators said the originator biologic was used in various dMARD treatment lines: first, 76.8%; second, 17.7%; third, 3.2 %; and fourth, 2.3%. At a median follow-up of 12.1 months, 50 patients (22.7%) presented with at least 1 nonserious adverse event, with 36 (16.4%) instances of disease re-activation, and 30 (13.6%) interruptions of SB4 treatment, mostly related to safety and efficacy.

They said the retention rates were 99.1% (210/212) at 6 months, 90.9% (150/165) at 12 months, and 81.5% (53/65) at 18 months, respectively.

Of the 30 interruptions in biosimilar treatment, 17 patients were switched back to the originator product; the remaining patients were given a different drug regimen. Investigators said age was the only significant predictor of interruption at 6 months.

Retention rates at 6, 12, and 18 months were not influenced by disease, bDMARD line, conventional synthetic DMARD combination, gender, disease duration or originator etanercept duration.

“Our real-life data confirm the safety profile of switching from ETN to SB4. In our patients, the data show a higher retention rate, when compared to other-real life registries data,” investigators wrote.

Astorri D, Ometto F, Friso L, Raffeiner B, Botsios C, Doria A. Use of TNF-inhibitors biosimilars in chronic inflammatory arthritides: a three-year experience in a large monocentric cohort of patients from the North-East Italy. Presented at: EULAR 2020 Congress; June 3-August 31, 2020. Abstract AB0274.

Bruni C, Gentileschi S, Capassoni M, et al. Safety and retention rate after switching from etanercept originator (ETN) to etanercept biosimilar (SB4) in inflammatory joint diseases: data from real life. Presented at EULAR 2020 Congress; June 3-August 31, 2020. Abstract AB0281.

EULAR

Studies on switching and retention for adalimumab and etanercept biosimilars yielded positive data, according to abstracts presented at the EULAR 2020 Congress.
 

EULAR Studies Explore Value of Biosimilar Switching

A survey of rheumatologists in France concluded that they generally have a good understanding of biosimilars but lack the confidence to use them, according to data presented at the EULAR 2020 Congress, the virtual meeting of the European League Against Rheumatism.

The study concerned the use of subcutaneously applied tumor necrosis factor inhibitor (SC TNFi) biosimilars, which have been available in France since 2015 at lower cost than reference products. There is no requirement in France that rheumatologists prescribe biosimilars or switch patients to them.

The findings mirror the results of a similar US-based study 

 last year in which rheumatologists expressed hesitancy about switching to biosimilars and extrapolating to uses beyond those the biosimilars were approved for.

French investigators surveyed 101 rheumatologists, 47.1% of whom were younger than 40 years and 92% of whom had authorization to prescribe TNFi.

According to the findings, 53.2% always prescribe biosimilars when prescribing TNFi for the first time, and 78.5% prescribe TNFi biosimilars 90% of the time.

Investigators said 30.6% of French rheumatologists never switch patients from originator drugs to biosimilars. Those who switch patients to biosimilars do it more than 75% of the time.

In the survey, 96.5%, 87.1%, and 91.8% agreed that biosimilars are as efficient, are as safe, and have the same immunogenicity profile as originator products, respectively.

Among rheumatologists who prescribe biosimilars in more than 90% of cases, 77.4% correctly answered no to the question “biosimilars and originators have to be compared in phase III studies for each indication for which the originators received marketing approval.”

Among those who prescribe biosimilars less than 90% of the time, just 31.2% answered this question correctly, indicating to the investigators that those who prescribe biosimilars as initial treatments tend to be equipped with better knowledge of biosimilars. Investigators said this finding was significant (

Rheumatologists were also asked whether there is enough experience with biosimilars. Most rheumatologists who switch to biosimilars more than 75% of the time answered this question in the affirmative, and just 25.4% in this group said there isn’t enough experience with biosimilars.

The same question was asked of those who switch to biosimilars less than 75% of the time. Investigators said a majority of them (57.7%) answered that there isn’t enough experience with biosimilars. This finding also was significant (

De Chateaubriant A, Ingrand P, Gervais E. Anti-TNF biosimilars: how knowledge and belief influence prescription. Presented at: EULAR 2020 Congress; June 3-August 31, 2020. Abstract AB1162.

A study presented at the European League Against Rheumatism conference suggested that French rheumatologists have good knowledge of biosimilars but lack the confidence to use them.

French Rheumatologists Lack Confidence in Biosimilars, Study Says

A rituximab biosimilar (Truxima) in combination with lenalidomide and acalabrutinib (R2A) in patients with relapsed or refractory aggressive B-cell lymphoma was tolerable and effective, according to findings 

at EHA25 Virtual, the annual meeting of the European Hematology Association.

In 13 patients who underwent disease assessment following treatment with the R2A regimen, the overall response rate was 69% and the complete response rate was 31%. The 6-month progression-free survival rate was 83%. Just 1 patient experienced disease progression after an initial objective response.

The rituximab product was developed by Celltrion Healthcare and study participants were enrolled in the Republic of Korea.

“By incorporating biosimilar rituximab into combination therapies alongside new drugs, the overall cost burden can be reduced, enhancing patient access,” said Youngil Koh, PhD, associate professor at Seoul National University Hospital and lead researcher for the trial in a statement.

Diffuse large B-cell lymphoma (DLBCL) is a subtype of non-Hodgkin lymphoma that accounts for about 30% to 40% of adult cases. Although global epidemiological data are limited, DLBCL’s estimated incidence is 7 cases per 100,000 individuals. B-cell lymphoma is aggressive and often diagnosed in late stage.

About 30% to 40% of patients who have had B-cell lymphoma relapse, and 10% have refractory disease. Without treatment, patients with relapsed or refractory disease have a life expectancy of 3 to 4 months.

Investigators said 73% of patients enrolled had non-germinal center B-cell—like (non-GCB) DLBCL. Patients received rituximab 375 mg/m

 daily intravenously, lenalidomide 20 mg once daily on day 1 to day 21, and acalabrutinib 100 mg twice daily on day 1 to day 28. Each cycle of treatment was delivered over 4 weeks, and each patient received 6 cycles. Responders received acalabrutinib maintenance for up to one year.

The phase 2 study ran from July 2019 to February 2020, and median follow-up was 3.2 months for 22 patients enrolled. Dosage was reduced in 3 and 1 patients for lenalidomide and acalabrutinib, respectively, due to hematological toxicity. During a total of 61 treatment cycles, 3 patients experienced higher than grade 2 toxicity for neutropenia, thrombocytopenia, and skin toxicity, which was the most common adverse event reported and occurred in 4 (18%) patients.

“The data indicate that the R2A regimen was therefore well tolerated in Korean relapse/refractory B-cell lymphoma patients, with initial analysis in non-GCB DLBCL patients showing a promising response,” investigators wrote.

 a prequalification to Truxima, making it the first rituximab biosimilar to be certified for use by the organization.

Truxima is currently marketed in the United States under the name Rituxan and in the European Union as MabThera. It 

Truxima is a monoclonal antibody that works by binding to CD20 cells on the surface of B-cells and mediates the destruction of cancer cells.

Koh Y, Park C, Byun Jm et al. Rituximab, lenalidomide and acalabrutinib (R2A) for relapsed/refractory aggressive B-cell lymphoma: interim analysis reporting good tolerability and potential durable response. Presented at EHA25 Virtual; June 11-21, 2020. Abstract EP1272.

A rituximab biosimilar developed by Celltrion Healthcare demonstrates safety and efficacy in patients with relapsed or refractory aggressive B-cell lymphoma, in findings presented at EHA25 Virtual, the annual meeting of the European Hematology Association.
 

Celltrion Biosimilar Shows Efficacy in DLBCL Combination

In studies presented this month at the European E-Congress of Rheumatology 2020, investigators revealed 

 for the infliximab biosimilar CT-P13 (Inflectra, Remsima), which is developed by Celltrion of Incheon, Republic of Korea.

The studies concerned the influence of body mass on response for CT-P13 subcutaneous (SC) in patients with active rheumatoid arthritis (RA), the correlation between antidrug antibody (ADA) positivity and clinical outcomes in patients with RA, and the potential savings in a market scenario where patients are treated with CT-P13 SC.

The post-hoc study of body mass on clinical response to CT-P13 SC demonstrated no statistically significant differences in response between patient cohorts stratified into under/normal weight (<25kg/m

), based on World Health Organization criteria.

Investigators said the mean change from baseline in disease activity score 28-joint count C reactive protein was —3.3, –3.1, and –3.3 at week 54, respectively. The duration of low disease activity up to week 54 was 26.2, 29.2, and 27.9 weeks, and the good or moderate European League Against Rheumatism responder rates were 84.1%, 80.3%, and 90.2% at week 54, respectively.

Patients in each cohort received at least 1 full dose of CT-P13 SC following intravenous induction in the initial treatment stage prior to week 30.

“The post-hoc results showed that there was no impact of [body mass index] BMI on the clinical responses of CT-P13 SC 120 mg biweekly in RA patients. Therefore, Remsima SC could be a promising therapeutic option regardless of BMI in RA patients,” said Rene Westhovens, a rheumatologist and one of the lead investigators in the trial.

In a second study, data from a multicenter, randomized, controlled trial demonstrated that ADA positivity and titer, or solution concentration, helped to predict pharmacokinetic profile and clinical response. Investigators said CT-P13 SC administration did not lead to a higher incidence of ADA compared with CT-P13 IV and no clinical differences between the formulations were observed.

In a third study, investigators concluded that self injection of CT-P13 could significantly reduce the burden on health care delivery. Their study suggested potential cost savings of $49.7 million over 5  years in the United Kingdom from the use of CT-P13 SC. They said the money saved was equivalent to the cost of CT-P13 treatment in an additional 4466 patients.

In a second scenario, investigators estimated potential savings of $350.7 million over 5 years based on real-world dose escalation up to 5 mg/kg. This, they said, would make it possible for an additional 30,839 patients to receive treatment with the SC formulation.

“With the pressure of meeting patient need and the increasing burden on health care systems, there is a greater demand than ever to deliver new and innovative treatment options that enable patients to live more independently, reduce the time spent in hospitals and in turn, lessen the pressures put on health care systems,” said Martin Perry, a consultant rheumatologist in the Department of Rheumatology at Royal Alexandra Hospital in Paisley, United Kingdom.  

Read more about CT-P13 and a recent study that may have helped to allay concern among gastroenterologists that there is not enough evidence to support use of the agent in 

The infliximab biosimilar CT-P13 delivered positive results in studies presented at the European League Against Rheumatism's European E-Congress of Rheumatology 2020.

Celltrion's Infliximab Demonstrates Value in Trio of Studies

The overall response rate (ORR) was 88% in an interim analysis study of a Sandoz rituximab biosimilar evaluated in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with CD20-positive diffuse large B-cell lymphoma (DLBCL), according to data presented at EHA20 Virtual, the 25th European Hematology Association (EHA) Congress.

The international REFLECT trial was the first prospective postapproval study to evaluate a rituximab biosimilar in this context. The study employed Sandoz’s rituximab biosimilar Rixathon (SDZ-RTX), which is approved in Europe, Japan, Australia, and Switzerland, among more than 20 countries and regions, for all indications of reference rituximab.

The efficacy and safety data presented this month at EHA20 Virtual confirmed 

from REFLECT released in 2019 at meetings of the American Society of Clinical Oncology and EHA, investigators said.

The primary end point was complete response (CR) and secondary end points were overall response and progression-free survival at 24 months, safety, and quality of life. Of the patients enrolled (N = 170), 38% completed the first 12 months of observation, 41% were ongoing, and 21% discontinued by the data cutoff (8% discontinued because of progressive disease).

At the end of treatment, CR was 57% and partial response was 31%. Investigators said 61% and 29% reported enlarged lymph nodes and disease-related pain, respectively.

They said 32% of patients had nodal lesions >15 mm. Most had an Eastern Cooperative Oncology Group functional performance score of 0 (35%) or 1 (46%), and for 70%, the Karnofsky performance scale score for functional impairment was ≥70%.

Early-stage (I-IIB) disease, low-to-intermediate disease risk (International Prognostic Index 0-2), and known DLBCL symptoms were reported for 55%, 50%, and 30% of patients, respectively.

Treatment-related adverse events (AEs) were reported for 28% of patients, and the rates of serious AEs and treatment-related serious AEs were 37% and 7%, respectively. Investigators said 2.5% of patients died on treatment.

The most common AEs were organ related (83%), general disorders and administration site conditions (40%), blood and lymphatic system disorders (38%), gastrointestinal (33%), and nervous system (32%). Among these, 21% experienced fatigue; 24%, anemia; 12%, nausea; and 15%, polyneuropathy.

Investigators concluded their findings reconfirm the safety and efficacy profile for this treatment combination in patients with DLBCL treated in a real-world setting. No new safety concerns were observed.

Welslau M, Marschner N, Otremba B, Topaly J, Bittencourt da Silva L. REFLECT real-world evidence: non-interventional, prospective study update on the efficacy and safety of Sandoz biosimilar rituximab for the treatment of diffuse large b-cell lymphoma (DLBCL). Presented at: EHA25 Virtual; June 11-21, 2020. Poster EP1245. library.ehaweb.org/eha/2020/eha25th/293734

Investigators reported an 88% overall response rate for a Sandoz rituximab biosimilar in combination with chemotherapy in patients with CD20-positive diffuse large B-cell lymphoma.

Sandoz R-CHOP Combination Confirms Findings in REFLECT

Biosimilars face many barriers to uptake in the United States, but the federal government is working to change things, said Michael Kolodziej, MD, vice president and chief innovation officer at ADVI Health, who presented at the National Comprehensive Cancer Network’s 2020 Virtual Conference.

“The federal government is the largest purchaser of cancer care services in the world, and the Feds want biosimilars to be successful,” Kolodziej said. ADVI health is a business development service based in Washington, DC.

Kolodziej said that an executive order signed 2 years ago allowed Medicare Advantage programs to use 

, including biosimilars, and encouraged commercial payers to do the same.

“The idea was that payers had a lot of experience using step therapy. And when there’s a legitimate rationale for therapeutic equivalence and an opportunity to use market forces to reduce prices of drugs, Medicare Advantage plans will do it,” Kolodziej said.

However, step therapy requirements are often accomplished through the use of prior authorization.

Still, Kolodziej said it became “absolutely crystal clear how biosimilars fit into a step therapy strategy.” Supportive care drugs and anti-inflammatory drugs were the first to be included.

Kolodziej said that 75% of commercial health plans now use step therapy in some form and several health plans implemented it immediately after it was allowed in Medicare Advantage plans.

Another uptake barrier the administration attempted to fix was the rebate system. Rebates prevent biosimilars from gaining market share and protect the interests of reference drug manufacturers by undercutting the sticker price discounts of biosimilars, Kolodziej said.

Kolodziej mentioned that Medicare’s inability to negotiate drug prices further undercuts the potential savings from biosimilars.

“It's fair to say that the commercial health plans only care about the net cost of the drug, which means that whatever the sticker price is, which is what Medicare pays, doesn’t matter much to them if they can get a better deal,” said Kolodziej.

In 2018, the Trump administration proposed getting rid of rebates applied a the point of sale, meaning that better deals generated by rebates would go to the patient instead of health plan providers. The draft rule was “shot down” over concerns that removing rebates would make the net cost of drugs go up, Kolodziej said, adding there are congressional champions still fighting to resolve the problem.

“Don't give up on it yet. We have seen commercial payers continue to play this rebate game. We’ve seen it in the supportive care space in oncology, where if you have commercial health insurance, you might prefer the reference product. But give it some time. This is just too politically sensitive to go away,” said Kolodziej.

The International Pricing Index and CAP Program

Establishment of an international pricing index was proposed by the current administration to set certain drug prices in the United States based on international benchmarks. The policy also included a second component: the Competitive Acquisition Program (CAP).

CAP would replace buy-and-bill drug purchasing by physicians with a system under which the payer purchases the drug and provides it to the physician for administration, a process known as “white bagging.” It transfers control over drug purchases from physician to the payer.

“The mechanism only works, it only becomes lucrative for the health plan and good for the government, if they can select certain drugs and negotiate around those drugs. If you can’t do that, the CAP program really doesn’t generate any significant savings,” Kolodziej said.

Kolodziej doesn’t believe that CAP would be beneficial for cancer care. “In fact, it would be a catastrophy,” he said. “But CAP really is designed to manage formulary, and if you want to manage formulary, you use biosimilars.”

Kolodziej said that those who argue that lower prices won’t be enough to drive market uptake for biosimilars are wrong, citing the response to generic drugs as a key reason why.

“It turns out that generic drugs certainly come in at a discount, but it takes a while to get to that discount. [Data] show that until you get a fourth or fifth generic competitor, the price doesn't really go down,” he said.

Recently, therapeutic biosimilars have started to launch on the market at a 25% discount, which Kolodziej sees as promising for patient and physician acceptance despite 30% of oncologists reporting that they are skeptical about using biosimilars. “Twenty-five percent of a big number is a big number, and health plans have noticed,” he said.

 “We're at a very interesting point in this story, because I would say that it's clear that supportive care biosimilars have really made their way into a common usage,” said Kolodziej.

More from the NCCN 2020 Virtual Conference can be found 

NCCN  Virtual Annual Conference

Although biosimilar uptake has been slow in the United States, the current administration has enacted several policies to help speed up the process, according to Michael Kolodziej, MD, who presented at the National Comprehensive Cancer Network (NCCN) 2020 Virtual Conference.
 

Part 2: Kolodziej Discusses Biosimilar Support at NCCN Conference

A retrospective study of patients with anemia in myelofibrosis (MF) treated with biosimilar erythropoiesis-stimulating agents (ESAs) demonstrated this to be an effective and well-tolerated option, according to data to be presented at the EHA20 Virtual, the 25th European Hematology Association Congress.

The Italian study enrolled patients (N = 40) with MF who received biosimilar ESA (B-ESA) for at least 1 month to treat anemia (hemoglobin [Hb] ≤10 g/dL). B-ESA was given off label with patient consent.

Investigators reported anemia response (AR), without significant toxicities, and concluded that patients who achieved AR demonstrated a significant survival advantage compared with those who had no response (NR).

They also concluded that transfusion dependency at baseline was a negative predictor for AR, suggesting that outcomes could be improved via earlier B-ESA treatment in patients with MF.

AR included complete and partial responses (CR and PR, respectively). PR was defined as a transfusion decrease of more than 50% or sustained Hb increase between 1 and 2 g/dL.

The study included slightly more male than female patients and 21 patients with primary MF and 19 with secondary MF. Median age at baseline was 73 years. At start of treatment, 17.5% of patients were at high risk and 70% and 12.5% of patients at intermediate-2 and intermediate-1 risk MF, respectively.

Patients began treatment with B-ESA at a median of 8.5 months from MF diagnosis, and the median dose of B-ESA was 40,000 U/week subcutaneously. Investigators said 29 patents (72.5%) received B-ESA before, at start of, or during ruxolitinib treatment.

The median Hb level at baseline was 9.2 g/dL (range, 8.2-10.0), and just 3 patients were transfusion dependent.

Investigators said 34 patients (85%) achieved an AR, with 28 CR (70%), 6 PR (15%), and 6 NR (15%). The median time to response was 1.7 months, and median B-ESA exposure time was 12.4 months. Six patients (17%) lost response to therapy after a median 12.9 months.

“The only significant predictor of poor response rate was transfusion dependency at baseline (Fisher’s exact test, 

Inzoli E, Pugliese N, Renso R, et al. Use of biosimilar erythropoiesis stimulating agents for anemia in myelofibrosis: a multicenter real-life experience on 40 patients. Presented at: EHA25 Virtual; June 11-21, 2020. Abstract EP1119. library.ehaweb.org/eha/2020/eha25th/293608/elena.inzoli.use.of.biosimilar.erythropoiesis.stimulanting.agents.for.anemia.html?f=listing%3D0%2Abrowseby%3D8%2Asortby%3D1%2Asearch%3Dbiosimilar

Investigators produced what they described as the first evidence supporting the use of biosimilar erythropoiesis-stimulating agents (ESAs) in patients with myelofibrosis-related anemia.

Biosimilar ESA Is Effective in Myelofibrosis Anemia

An extension study of a trastuzumab biosimilar (SB3, Ontruzant) versus reference trastuzumab (TRZ) supports a hypothesis that a downward "drift" in antibody-dependent cell-mediated cytotoxicity (ADCC) contributed to lower event-free survival (EFS) and overall survival (OS), according to data 

at ASCO20 Virtual, the annual meeting of the American Society of Clinical Oncology.

The study, an extension of a phase 3 trial, assessed long-term cardiac safety and efficacy in patients with HER2-positive early or locally advanced breast cancer treated with biosimilar or TRZ.

 (N = 875), 13 were classified as having a drift in ADCC activity, and the remainder were considered to have ADCC activity in the normal range. Investigators in this study had previously observed that ADCC appears to correlate with EFS.

“ADCC is thought to be an important contributor to the efficacy of trastuzumab, and amplification of ADCC activity could be a promising area of research,” the investigators noted in the October 2019 report.

In the extension study, 367 patients were enrolled from the main study after completing neoadjuvant-adjuvant therapy, 187 on the SB3 arm and 181 on 1 of 2 reference product arms: nondrifted TRZ (n = 55) and drifted TRZ (n = 126).

The investigators reported that the incidence of asymptomatic significant left ventricular ejection fraction (LVEF) decrease was comparable between the biosimilar and TRZ groups. “All of the patients recovered with LVEF above 50%.” There were no instances of congestive heart failure, cardiac death, or other significant cardiac conditions during the follow-up.  

Further, there was no statistically significant difference in EFS or OS between SB3 and TRZ. The 4-year EFS rates for SB3 and TRZ were 83.4% and 80.7% (HR, 0.77; 95% CI, 0.47-1.27), respectively; and the 4-year OS rates were 94.4% and 89.6% (HR, 0.53; 95% CI, 0.24-1.16).

With regard to EFS between SB3 and nondrifted TRZ, an ad-hoc analysis revealed no difference (HR, 1.60; 95% CI, 0.58-4.40; 

 = .362). There also was no difference in OS between SB3 and nondrafted TRZ (HR, 0.97; 95% CI, 0.11-8.50; 

However, between drifted TRZ and nondrifted TRZ, differences were observed for EFS (HR, 5.50; 95% CI, 1.81-16.65; 

 = .003) and OS (HR, 15.35; 95% CI, 1.78-132.69; 

The Investigators concluded that “comparable long-term cardiac safety and survival at the 4-year follow-up supports biosimilarity between SB3 and TRZ,” but “ad-hoc analysis results by ADCC status suggest a possible correlation between ADCC and clinical efficacy,” meriting further study.

For further biosimilars coverage of ASCO20 Virtual, click 

ASCO

Downward “drift” in batches of reference trastuzumab shed more light on the importance of antibody-dependent cell-mediated cytotoxicity on survival, investigators reported at ASCO20 Virtual, the annual meeting of the American Society of Clinical Oncology.
 

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