Safe Biologics

On April 27th, the journal Digesitve Diseases and Sciences published a editorial by Frank I. Scott, MD entitled “Infliximab Versus Biosimilars for IBD: Is It Better to Fight Than Switch?. Dr. Scott heads the Crohn’s and Colitis Center, Division of Gastroenterology and Hepatology, Department of Medicine, at the University of Colorado.

In the editorial, Dr. Scott discusses a study appearing in the April issue of Digestive Diseases and Sciences which presents the most comprehensive review to date of data supporting non-medical switching between infliximab and CT-P13 (marketed as Inflectra).

Forty-nine randomized controlled trials, observational studies, and conference abstracts were included in the authors’ review. Of these, only three of the reviewed studies were randomized controlled trials, including NOR-SWITCH and two as-yet-unpublished IBD-specific trials. From the article:

Collectively, these studies demonstrated no significant difference in sustained clinical response between bio-originator infliximab and its biosimilars.

Despite these reassurances, significant questions remain regarding the long-term safety of non-medical switching strategies. While the summarized data in their review, for the most part, suggest that switching between bio-originator infliximab and CT-P13 is safe, the data quality is limited. As noted previously, only one randomized controlled trial has been published, with two additional studies included which are pending publication. Significant heterogeneity among existing observational studies limits their interpretation as well. Further, while non-medical switching policies have been enacted, there has been incomplete pharmacovigilance reporting on the patient level and pharmacoepidemiologic evaluation at the population level. Lastly, since the available data pertain to single switches from originator compound to CT-P13, they incompletely reflect the multi-directional switching that may occur in practice with non-medical switching.\

Unfortunately, loss of response to therapies in both CD and UC is well described, obscuring the differentiation of loss of response due to expected rates versus that which can be attributed to the switch itself. Accurately measuring this risk will be vital in considering the true medical, ethical, and financial burdens related to non-medical switching. Further, it is unlikely that such risk–benefit balances are identical across different biologics, as accumulating data suggest that specific agents are preferable in UC versus CD and vice versa.

In conclusion, the review by [the authors] summarizes the current state of the evidence with regards to non-medical switching for bio-originator infliximab and CT-P13. While the totality of evidence appears reassuring, significant questions remain regarding the quality of and comparability of these data. Further prospective research is required before non-medical switching can be widely adopted, and long-term observation is requisite when it does occur to ensure the safety and effectiveness of such strategies.

Read the study here and the accompanying editorial here. 

On April 6th, ASBM submitted comments on the FDA’s recently published draft guidance outlining its current thinking on presenting data and information in a truthful and non-misleading way about biosimilars and reference products in FDA-regulated promotional materials.

It addresses questions companies may have when developing these kinds of materials and provides examples that can help with specific situations biosimilar and reference product companies may encounter.

The Draft Guidance is among the deliverables in the FDA’s Biosimilars Action Plan (BAP) that outlines four key strategies to accelerate biosimilar competition, including supporting market competition and providing clearer direction to industry on the development of promotional materials for medical products.

ASBM’s comments reflected observations from ASBM Chair Madelaine Feldman, MD; Advisory Board Chair Philip Schneider MS, FASHP, FFIP; and Steering Committee Member Andrew Spiegel, executive director of the Global Colon Cancer Association. From the comments:

One thing we’ve seen across Europe is that as more and more biosimilars are launched in a given product class, competition drives prices downward, discounts increase substantially, and biosimilar market share goes up. So we know what to expect, and what things to look for.

Thankfully we are seeing this happening in the US. Here we have a biosimilar filgrastim that launched with a relatively low 15% discount over its reference product. Today, with increased competition, that product has attained a majority share of the US market in its class with 55%. Late last year we saw the first rituximab biosimilar launch at a 10% discount over the reference product, and only a few months later the second launched at a larger, 24% discount.

We have every reason to believe this pattern will continue as we see it becoming routine for 3, 4, or 5 biosimilars approved for a reference product, and as these come on the market, manufacturers will continue to compete on price- moving from low discounts, to higher discounts.

ASBM representatives participated in a joint FDA/FTC Public Workshop held on March 9th at the FDA’s headquarters to discuss the guidance; as well as a related half-day event sponsored by the Hatch Center, Pfizer, and the Biosimilars Forum the following day, entitiled “Biosimilars: Breaking through the Barriers’.

Read ASBM’s comments in full here.

View all submitted comments here. 

On March 25th, the Journal of the Generics and Biosimilars Initiative (GaBI Journal) published a whitepaper entitled Policy recommendations for a sustainable biosimilars market: lessons from Europe. The paper was authored by ASBM Executive Director Michael Reilly and Advisory Board Chair Philip Schneider.

1. Physicians should have the freedom to choose between off-patent originator biologicals and available biosimilars and to act in the best interest of their patients based on scientific evidence and clinical experience.
2. Tenders should be designed to include multiple value-based criteria beyond price, e.g. education, services, available dose strengths, and provide a sufficient broad choice (multi-winner tenders versus single-winner tenders) to ensure continuity of supply and healthy competition.
3. A level playing field between all participating manufacturers is the best way to foster competition; mandatory discounts which place artificial downward pressure on manufacturers do not engender a sustainable market environment.

The paper will also appear in Volume 9, issue 2 of the Gabi Journal 2020 print edition to be published in June.

Read the whitepaper here. 

On March 9th and 10th, two major meetings were held in the nation’s capitol to discuss the barriers to the success of biosimilars in the U.S. marketplace.

The first meeting was a joint FDA/FTC Public Workshop held on March 9th at the FDA’s headquarters. The second was a half-day event sponsored by the Hatch Center, Pfizer, and the Biosimilars Forum the following day and featured a keynote address from Health and Human Services (HHS) Secretary Alex Azar.

ASBM representatives participated in both events. Dr. Feldman, Dr. Schneider, and Andrew Spiegel provided comments at the FDA/FTC meeting and posed questions to the panelists at the Hatch/Pfizer event.

A key theme at both meetings was the importance of educating physicians and patients about biosimilars, as well as addressing commercial barriers to biosimilar uptake posed by patent litigation, insufficient price transparency, and the PBM rebate system.

One presenter identified the chief barriers to biosimilar uptake as physicians (who needed educational outreach to increase their familiarity and comfort with biosimilars) and payers (whose policies can sometimes impede utilization, and need to be addressed). ASBM Advisory Board Chair Philip Schneider addressed these concerns in his remarks at the FDA/FTC workshop:

Our recent survey of 579 European biologic prescribers show high knowledge and high confidence in biosimilars. Depending on country, between 82% and 93% of prescribers considered themselves familiar or very familiar with biosimilars. Between 80% and 99% would feel comfortable prescribing a biosimilar to a new treatment-naïve patient. Between 46-76% would be comfortable switching a stable patient.

if the premise behind today’s proceedings is valid – that biosimilar uptake is strongly tied to physician confidence, the high physician confidence in biosimilars across the board should correlate with a consistently high uptake across the board.

Yet if we look at the biosimilar market shares across the six countries we surveyed, there is a very wide variation, and variation among biosimilars in different product classes. For example, market share for the Epoetin biosimilar ranged from 6-84%.  There are similar ranges for other biosimilars.

Clearly there are other factors besides physician confidence, which is uniformly high across the countries. These factors likely include differences between each country’s payer policies, differences in the length of time a biosimilar has been on the market, the number of biosimilars in a given product class, the discount of each product relative to the originator product, and other factors.

ASBM Steering Committee Member Andrew Spiegel, who attended both events, characterized the U.S. biosimilars market as “a success story” in his remarks at the Hatch/Pfizer event. In addition to the Zarxio example, Spiegel also cited the example of the first rituximab biosimilar launched last year by Teva with a 10% discount. The second one, he pointed out, launched last month by Pfizer, has a 22% discount.

“As we look to Europe as a model, we see the key is many different products competing and putting downward pressure on price. The greater the discounts, the greater the market share- it’s encouraging to see this beginning to happen in the U.S. as well,” said Spiegel.

Read the comments submitted to the FDA/FTC by Dr. Feldman, Dr. Schneider, and Mr. Spiegel.

On March 9th and 10th, two major meetings were held in the nation’s capitol to discuss the barriers to the success of biosimilars in the U.S. marketplace.

The first meeting was a joint FDA/FTC Public Workshop held on March 9th at the FDA’s headquarters. The second was a half-day event sponsored by the Hatch Center, Pfizer, and the Biosimilars Forum the following day and featured a keynote address from Health and Human Services (HHS) Secretary Alex Azar.

ASBM representatives participated in both events. Dr. Feldman, Dr. Schneider, and Andrew Spiegel provided comments at the FDA/FTC meeting and posed questions to the panelists at the Hatch/Pfizer event.

A key theme at both meetings was the importance of educating physicians and patients about biosimilars, as well as addressing commercial barriers to biosimilar uptake posed by patent litigation, insufficient price transparency, and the PBM rebate system.

One presenter identified the chief barriers to biosimilar uptake as physicians (who needed educational outreach to increase their familiarity and comfort with biosimilars) and payers (whose policies can sometimes impede utilization, and need to be addressed). ASBM Advisory Board Chair Philip Schneider addressed these concerns in his remarks at the FDA/FTC workshop:

Our recent survey of 579 European biologic prescribers show high knowledge and high confidence in biosimilars. Depending on country, between 82% and 93% of prescribers considered themselves familiar or very familiar with biosimilars. Between 80% and 99% would feel comfortable prescribing a biosimilar to a new treatment-naïve patient. Between 46-76% would be comfortable switching a stable patient.

if the premise behind today’s proceedings is valid – that biosimilar uptake is strongly tied to physician confidence, the high physician confidence in biosimilars across the board should correlate with a consistently high uptake across the board.

Yet if we look at the biosimilar market shares across the six countries we surveyed, there is a very wide variation, and variation among biosimilars in different product classes. For example, market share for the Epoetin biosimilar ranged from 6-84%.  There are similar ranges for other biosimilars.

Clearly there are other factors besides physician confidence, which is uniformly high across the countries. These factors likely include differences between each country’s payer policies, differences in the length of time a biosimilar has been on the market, the number of biosimilars in a given product class, the discount of each product relative to the originator product, and other factors.

ASBM Steering Committee Member Andrew Spiegel, who attended both events, characterized the U.S. biosimilars market as “a success story” in his remarks at the Hatch/Pfizer event. In addition to the Zarxio example, Spiegel also cited the example of the first rituximab biosimilar launched last year by Teva with a 10% discount. The second one, he pointed out, launched last month by Pfizer, has a 22% discount.

“As we look to Europe as a model, we see the key is many different products competing and putting downward pressure on price. The greater the discounts, the greater the market share- it’s encouraging to see this beginning to happen in the U.S. as well,” said Spiegel.

Read the comments submitted to the FDA/FTC by Dr. Feldman, Dr. Schneider, and Mr. Spiegel.

From March 2-4, ASBM representatives led multiple sessions at the World Biosimilar Congress USA, part of the Festival of Biologics USA 2020 held in San Diego, CA.

ASBM Steering Committee Member Andy Spiegel, executive director of the Global Colon Cancer Association, participated in an opening “fireside chat” with Leah Christl, PhD. Dr. Christl formerly led the FDA’s Therapeutic Biologics and Biosimilars Staff (TBBS) in the Office of New Drugs (OND). Mr. Spiegel also moderated a panel discussion on “How to build a sustainable biosimilars market.”

ASBM Advisory Board Chair Philip Schneider, MS, FASHP moderated a panel discussion on “What do policymakers need to address for biosimilars to become more accessible?” and chaired a session on “Biosimilars in healthcare policy.” Topics examined in these sessions included: “Do biosimilars create real competition?” “Reimbursement in biosimilars;” and “Originators and biosimilars: getting the balance right.”

Following the conference, Dr. Schneider offered the following observations on the various discussions:

• The US is catching up to the EU in the approval of both biologics and biosimilars, despite Europe’s nearly 10-year lead.
• Biosimilars are beginning to place downward pressure on the prices of biologics; both reference products and biosimilars.  Metrics for success are prices, not market share.
• There is agreement on the importance of sustainability in the biologics and biosimilars market to promote innovation and competition. Multi-product tenders are one way to support this.
• Prescriber choice remains an important issue among most players.

Learn more about the World Biosimilar Congress USA 2020 Meeting here.