Biosimilars Updates

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Evidence-Based Oncology, December 2018, Volume 24, Issue 13

Community Oncologists Divided on the Value of Biosimilars

During the Community Oncology Alliance (COA) Payer Summit, held October 29-30, 2018, The Center for Biosimilars® had the opportunity to sit down with several oncologists to discuss their opinions on and experiences with biosimilars.

When asked how he feels about the upcoming availability of anticancer biosimilars as treatment options, Lalan Wilfong, MD, executive vice president of Quality Programs at Texas Oncology, was hopeful. “I think most practices are looking forward to the development of biosimilars, similar to the generic market1 when generics were introduced, that’s when prices actually started falling for cancer therapy,” Wilfong said at the event.

Kashyap Patel2, MD, CEO of Carolina Blood and Cancer Care echoed Wilfong’s statement, but also explained that he believes biosimilars have a central role to play in the US healthcare system as a whole, not just in cancer care. Patel speaks from personal experience; he presented data at ASCO’s Quality Care symposium that found that “7% of total savings of the Oncology Care Model came from switching to biosimilar [granulocyte colony-stimulating factor] G-CSF, [filgrastim]” in his own health system.

However, not all oncologists were in agreement about the value of biosimi- lars. When asked if she believes biosimilars have a role in bringing down drug costs, Kavita Patel, MD, nonresident senior fellow at the Brookings Institution, said, “No. I think that there are limited numbers of biosimilars, and I don’t think that the biosimilars are priced at such a degree that—when you have drugs that cost hundreds of thousands of dollars to millions of dollars—having a biosim- ilar even for something with a large clinical indication, it’s like a fraction of the overall drug spend.”

Although biosimilars have the potential to bring down costs, she conceded, some factors in the marketplace need to be addressed first before they begin generating significant savings.

“I think we need more biosimilars, which the FDA has signaled, and we need more biosimilars that are priced at such a delta to make an appreciable difference,” she said. “There are some pretty ‘hot’ oncology drugs that have a biosimilar available, but then the way the practice might have already set up their pharmacy or their network, they’ve already kind of locked in to certain manufacturers, making the biosimilar less attractive.”

One specific need reiterated by each oncologist was that, in order for physicians to feel more comfortable prescribing biosimilars in their own practice, education on the safety and efficacy data associated with the products is key going forward.

REFERENCES:

1. Cate Lockhart, PharmD, PhD: similarities between biosimilars and generics. The Center for Biosimilars® website. www.centerforbiosimilars.com/interviews/cate-lockhart-pharmd-phd-similarities-between-biosimilars-and-generics. Published June 25, 2018. Accessed November 9, 2018.

Biosimilars Can Play a Key Role in Value-Based Care, Review Says

2. Dr Kashyap Patel: biosimilars and value. The Center for Biosimilars® website. www.centerforbiosimilars.com/ interviews/dr-kashyap-patel-biosimilars-and-value. Published December 7, 2017. Accessed November 9, 2018.Given the high burden associated with cancer in the senior population, and given the increasingly high cost of cancer care, there is a growing interest in value-based oncology care payment models, particularly within CMS.

A recent review1, authored by The Center for Biosimilars® advisory board member Kashyap Patel, MD2, and colleagues, provides an overview of value-based care models and discusses the role of biosimilars in meeting these models’ objectives.

The review, appearing in Cancer Management and Research, notes that US spending on cancer care grew from $27 billion in 1990 to $124 billion in 2010, with spending levels expected to reach $157 billion by 2020. Globally, spending on oncology and supportive care reached $100 billion in 2014. Among the fastest-growing drug classes in oncology are monoclonal antibodies—many of which are targeted by biosimilar developers—which account for 35% of US oncology spending.

To help address skyrocketing costs, CMS has developed value-based care programs that reward providers with incentives for improving the quality of care they provide to Medicare beneficiaries. These programs seek to move away from the fee-for-service (FFS) model that incentivizes high-quantity (although not necessarily high-quality) care.

In 2016, CMS implemented the Quality Payment Program, which offers payment to providers either through the Merit-based Incentive Payment System or through Advanced Alternative Payment Models, one of which is the Oncology Care Model (OCM).

The OCM is a voluntary program that seeks to provide higher-quality care at the same or lower cost to Medicare than traditional FFS payments. The OCM links payments to provider performance based on meeting quality metrics and making practice reforms.

Biosimilar therapies offer increased affordability and access—as well as improved outcomes and improved health-related quality of life—to patients treated in the OCM model; using lower-cost biosimilar granulocyte colony-stimulating factor therapies,3 for example, can reduce the incidence of neutropenia, allowing for increased dose administration of patients’ primary treatments and improved survival.

Not only may biosimilars, themselves, be offered at more affordable prices than biologics—as has been demonstrated in experience with biosimilar filgrastim—but they also may drive down overall prices in a given class as a result of market competition, producing substantial US cost savings. These savings, which have the potential to grow with upcoming availability of biosimilar epoetin alfa and biosimilars of targeted therapies, could help physicians to meet the OCM objective of improving patient care while reducing costs.

However, write Patel and colleagues, “Realization of cost savings possible from biosimilars...will require that biosimilars are utilized.” Current gaps in physician education4 on biosimilars have limited the use of these agents, making the need for provider education all the more pressing.

REFERENCES:

1. Patel KB, Arantes LH Jr, Tang WY, Fung S. The role of biosimilars in value-based oncology care. Cancer Manag Res. 2018;10:4591-4602. doi: 10.2147/CMAR.S164201.

2. Davio K. Patient-administered biosimilar and follow-on filgrastim pose opportunity for savings. The Center for Biosimilars® website. www.centerforbiosimilars.com/news/patientadministered-biosimilar-and-followon-filgrastim-pose-opportunity-for-savings. Published August 13, 2018. Accessed November 1, 2018.

3. Davio K. Despite educational efforts, providers still lack knowledge on biosimilars. The Center for Biosimilars® website. www.centerforbiosimilars.com/conferences/acr-2018/despite-educational-efforts-providers-still-lack-knowledge-on-biosimilars. Published October 18, 2018. Accessed November 1, 2018.

As Reassuring Data on Anticancer Biosimilars Grow, ESMO Ups Its Biosimilar Education

The European Society for Medical Oncology (ESMO) 2018 Congress, held October 19-23, 2018, in Munich, Germany, featured multiple presentations on biosimilars in oncology, all of which are contributing to the body of evidence that points to the safety and efficacy of these products.

Specifically, one study1 closely investigated the efficacy of the trastuzumab biosimilar SB3, approved in the European Union and sold as Ontruzant, with the reference product in patients with early breast cancer (EBC).

The study enrolled 800 total patients, with 402 given the biosimilar and 398 given the reference trastuzumab. Patients were treated for 8 cycles concurrently with chemotherapy. Patients underwent surgery, and then 10 more cycles of SB3 or the reference.

The primary endpoint was breast pathologic complete response (bpCR) rate, which was measured at 51.7% for SB3, and at 42.0% for the reference, with an adjusted difference of 10.7% (95% CI, 4.13-17.26).

Overall, the researchers found that the analysis results of bpCR, total pathologic response rate, and overall response rate leaned toward greater efficacy in patients treated with SB3 compared with the reference product.

In another study,2 researchers conducted a systematic literature review to examine whether demonstrating bioequivalence in terms of efficacy is different in EBC versus metastatic breast cancer (MBC) when patients are treated with a biosimilar trastuzumab, Ogivri (trastuzumab-dkst), versus the reference product.

In total, researchers identified 8 phase 3 clinical trials for 6 proposed biosimilars. Of these, 4 were conducted in EBC, and 4 were in MBC. In all trials, the proposed biosimilar was found to be equivalent to the reference in terms of efficacy. Two biosimilars showed equivalent efficacy in both the EBC and MBC settings.

Regardless of clinical setting, all biosimilars analyzed demonstrated equivalent efficacy to reference trastuzumab.

Despite such reassuring data for biosimilars, however, many stakeholders have noted that lack of provider education on biosimilars is holding back progress with uptake of these products.

Concurrently with the meeting, ESMO published a new paper3 on the integration of biosimilars into routine oncology practice. The paper reports that, when questioned about their knowledge of and comfort with biosimilars, many oncologists exhibited only “moderate confidence” in their understanding of key concepts related to biosimilar drug development and use. Nearly 87% of respondents said that they need more educational activities on the subject.

The paper also found that extrapolating the use of a biosimilar to all indications approved for the reference product seemed to be the most common misunderstanding among physicians, nurses, and patients alike.

“It is a very difficult concept to explain outside of the regulatory setting,” said Elena Wolff-Holz, MD, of the European Medicines Agency. “This is what educational activities should focus on—not just for oncologists, but for all healthcare professionals and for patients,” said Josep Tabernero, MD, PhD, MSc, president of ESMO.

Among ESMO’s attempts to provide such education are its position paper on using biosimilars and its multistakeholder discussion forums held both at this year’s congress and previously at the 2017 meeting.

REFERENCES:

1. Castan JC, Pegram M, Pivot X, et al. Subgroup analyses of efficacy from a phase III study comparing SB3 (trastuzumab biosimilar) with reference trastuzumab in early breast cancer patients. Presented at: European Society for Medical Oncology 2018 Congress; October 19-23, 2018; Munich, Germany. Abstract 217P. https://cslide. ctimeetingtech.com/esmo2018/attendee/confcal/session/calendar?q=217P&c=abs.

FDA Approves Celltrion's Rituximab Biosimilar, Truxima

2. Rugo HS, Curigliano G, Cardoso F, et al. Settings-based efficacy comparison of trastuzumab biosimilars in breast cancer: a systematic literature review. Presented at: European Society for Medical Oncology 2018 Congress; October 19-23, 2018; Munich, Germany. Abstract 324P. https://cslide.ctimeetingtech.com/esmo2018/attendee/ confcal/session/calendar?q=217P&c=abs. 3. Wolff-Holz E, Garcia Burgos J, Giuliani R, et al. Preparing for the incoming wave of biosimilars in oncology. ESMO Open. 2018;3(6):e000420. doi: 10.1136/esmoopen-2018-000420.The FDA has approved Celltrion and Teva’s rituximab biosimilar, Truxima (rituximab-abbs). The biosimilar, referencing Rituxan, has been approved to treat adults with CD20-positive, B-cell non-Hodgkin lymphoma (NHL) either as monotherapy or in combination with chemotherapy.1

Like its reference product, Truxima has a label that carries a boxed warning alerting providers and patients to the risk of fatal infusion reactions, skin and mouth reactions, hepatitis B reactivation, and a rare but serious brain infection.

In a statement, FDA Commissioner Scott Gottlieb, MD, hailed approval of the drug as an example of the success of the agency’s Biosimilar Action Plan. “The Truxima approval is our third biosimilar approval in the past month. The growing pipeline of biosimilars is encouraging,” he said. “We’re seeing more biosimilar drugs gain market share as this industry matures. We’ll continue to make sure biosimilar medications are evaluated efficiently through a process that makes certain that these new medicines meet the FDA’s rigorous standards for approval.”1

Truxima’s approval follows a unanimous recommendation of approval by the FDA’s Oncologic Drug Advisory Committee (ODAC) in October 2018. In a vote on whether the totality of the evidence supported the licensure of the biosimilar, all 16 committee members voted yes, for reasons some voters enumerated as “overwhelming biosimilarity and clinical trial evidence” that “really sealed the deal.”2

The committee heard a review of data presented from various speakers, including advisory officials for the FDA who analyzed the drug’s data prior to the presentation. According to the FDA, although there were minor differences in clinically inactive compounds, the totality of the evidence suggested Truxima is highly similar to the reference product with no clinically meaningful differences.

Notably, while the reference rituximab also carries indications for inflammatory diseases including rheumatoid arthritis, Celltrion sought approval only for indications in oncology; when ODAC members asked about the reasoning behind only seeking an indication in NHL, a Celltrion representative stated that “We are only seeking approval in 3 [NHL] indications given the patent and exclusivity landscape at this time.”

Truxima, which is also approved and widely used in the European Union, is the 15th biosimilar, and the first rituximab biosimilar, approved by the FDA.

REFERENCES:

1. FDA approves first biosimilar treatment for adults with non-Hodgkin’s lymphoma [press release]. Silver Spring, MD: FDA newsroom; November 28, 2018. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ ucm627009.htm. Accessed November 29, 2018.

2. DiGrande S. ODAC unanimously recommends Celltrion’s biosimilar for rituximab for FDA approval. The Center for Biosimilars® website. centerforbiosimilars.com/news/odac-unanimously-recommends-celltrions-biosimi- lar-rituximab-for-fda-approval. Published October 10, 2018. Accessed November 29, 2018.