Safe Biologics

In the podcast, Spiegel explains how biologic medicines have extended the life expectancy of cancer patients, and how biosimilars can bring these patients new treatment options at reduced cost.

He also details concerns among the physician and patient community surrounding “non-medical switching“- forced switching by third parties such as insurance companies, for financial reasons rather than the health of the patient.
Download/Listen to the podcast here. 

Learn more about non-medical switching here. 

On January 25th, the American Hospital Association (AHA) joined the ever-growing ranks of those opposing the Most Favored Nation (MFN) model interim final rule. The rule should be withdrawn immediately, the American Hospital Association (AHA) said in a letter to CMS.
The MFN model reduces Medicare Part B payments for certain drugs and biologicals to no more than the lowest price the drug manufacturers receive in countries with a similar level of economic development. The AHA contends that the rule is not a serious attempt at drug pricing reform because it does not directly address the cost of drugs. Instead, the rule places financial burden on provider organizations and forces them to divert resources to purchase drugs necessary for patient care, the AHA said.

Opposition to the MFN rule has been broad and come from many quarters, including physicians, patient advocacy organizations, the pharmaceutical industry, hospital associations, and others.

Read more about the AHA letter here.

On January 19th, ASBM submitted comments on Draft Guidance issued November 19, 2020 by the FDA entitled “Biosimilarity and Interchangeability: Additional Draft Q&As on Biosimilar Development and the BPCI Act”
The document offers insights into how FDA will handle certain aspects of submissions and labeling for interchangeable biosimilars.

These include how an applicant may seek FDA review for licensure for an interchangeable biosimilar, and how a 351(a) BLA holder should proceed if it seeks licensure of its biological product under section 351(k) as biosimilar to or interchangeable with another biological product licensed under section 351(a) (a “reference product”). In addition, the document discusses recommendations for labeling of interchangeable biosimilars.

ASBM’s comments reiterated support for the FDA interchangeability standard, and for transparent labeling that facilitates informed treatment decision-making by healthcare providers and patients:

It is ASBM’s view that biosimilars and interchangeable biosimilars are two separate classes of medicines. The statutory requirements to achieve the designation of interchangeability are appropriately designed to necessitate a higher burden of proof, with a greater focus on the individual patient.

To meet these standards, ASBM believes a robust clinical program is required, such that it can be demonstrated, with near certainty, that the biosimilar product will produce the same clinical result as the reference product in any given patient, AND in the case of a biological product administered more than once to a patient, the risk in terms of safety or diminished efficacy of alternating or switching between use of the biosimilar product and the reference product is not greater than the risk of using the reference product without such alteration or switch.

Regarding Q.I.27 (Labeling of interchangeable biosimilars), ASBM believes that transparent labeling for biosimilar and interchangeable biosimilar products is critical for building physicians’ confidence in the safety of these medicines. Inclusion of approval and safety information generated by the biosimilar sponsor and transparency concerning studied versus extrapolated indications would provide a more comprehensive label to inform physician and pharmacist decisions regarding their patients.

Once finalized, FDA will move the questions and answers from the draft guidance to its companion Final Questions and Answers Guidance on biosimilar development.
Read the Draft Guidance here.
 

ICYMI: US Biosimilar Market on Pace with Europe
In January, the ASBM-authored whitepaper “US Biosimilars Market on Pace with Europe” was published in the print edition of GaBI Journal 2020 Issue 4. The paper is co-authored by ASBM’s Chair Madelaine Feldman and Executive Director Michael Reilly.

The paper demonstrates FDA is moving at approximately the same pace as EMA based on the number of approvals at the same time after implementation of its regulatory pathway:

• As of September 2020, approximately 10 years after implementation of the biosimilar approval pathway, 28 biosimilars have been approved by FDA, with 18 of those approvals granted in the last 2 years. (Note: this figure has since risen to 29 approvals with the  December 17 approval of Rianbi (rituximab-arrx), which launched January 2021). 
• For comparison, in the 10-year time period following the creation of Europe’s biosimilar regulatory pathway, EMA approved just 13 biosimilar products (some of which were marketed under several different brand names)
• Currently, there are 46 biosimilars approved in Europe; however, this fall to 35 when products approved in the US as follow on biologicals via the 505(b)(2) pathway, e.g. somatropin, insulin, teriparatide, or abbreviated new drug application (ANDA) are excluded. Furthermore, Europe’s filgrastim biosimilar Tevagrastim®/Ratiograstim® was approved as Granix® (tbo-filgrastim) in the US via a Biologic License Application (BLA) prior to the implementation of a biosimilars approval pathway and is not included in the US biosimilar count.

In addition, US biosimilars have gained significant share in the majority of therapeutic areas in which they have been introduced, ranging on average from 20% to 25% within the first year of launch, with some projected to reach greater than 50% within the first 2 years:

• As expected, first-to-market biosimilars tend to capture a greater portion of the segment compared to later entrants. Filgrastim biosimilars have been on the market the longest at 5 years and have achieved a 72% share.
• Bevacizumab and trastuzumab biosimilars, launched in 2019-2020 have approximately 40% share.
• Rituximab and infliximab have had the most limited adoption, with approximately 20% market share.

Read the full whitepaper here. 

Missed last month’s ASBM Newsletter? Read it Here.

DIA Latin America Regulatory Conference

Virtual – February 22-23, 2021

World Biosimilar Congress USA 2021

Virtual – March 29-31, 2021

WHO 72nd INN Consultation

Geneva, Switzerland/Virtual – April 13, 2021

Biologics Europe Online (Webinar)

Virtual – April 26-27, 2021

The paper examined biosimilar substitution policies across Europe, looking for commonalities among them which led to successful and sustainable biosimilar markets. The paper found that across Europe, biosimilars have:

• Increased competition
• Reduced unit cost of both originator and biosimilars compared to price levels prior to the arrival of biosimilars
• Increased volume consumption of molecules with biosimilar competition thus expanding market access and optimizing patient dosing
• Alleviated budget pressures by providing headroom to fund novel treatment solutions

While the policies by which this has been achieved vary somewhat between countries, the paper reveals that all major European markets share the following features:

• Automatic substitution for biologicals is forbidden
• All approved biologicals, i.e. originators and their biosimilars, are available on the market and are reimbursed when prescribed
• Reimbursement decisions on novel treatment solutions are independent from biosimilar use and uptake
• The time from market approval to first product sales for biosimilars is shorter than the time to first sales of novel medicines

Read the whitepaper here. 

The World Health Organization (WHO) recently released the results of a 20-country survey which identified barriers to biosimilar adoption, the Center for Biosimilars reports. Entitiled “Regulatory challenges with biosimilars: an update from 20 countries”, the survey was a follow-up to one conducted ten years prior. While most of the issues identified in the earlier survey have been resolved, the authors report, a few remain including the lack of a consistent international standard for biologic naming. “There is still no consensus among countries on the naming and labeling of biosimilars,” they observe, and the WHO does not provide specific nomenclature for biosimilars.

Some countries including Canada and those in Europe, use the brand name and international nonproprietary name (INN) that latter of which is shared between the reference biologic and all its biosimilars. Other countries, including the United States and Japan use a suffix or other identifier as part of the name.

The authors stressed that naming and labeling are important for good pharmacovigilance, which they call “essential for establishing the safety and efficacy of interchangeability of biosimilars.” There are concerns, they say, about “prescription mix‐ups, unintentional switching, and questions on traceability.” To address these concerns, the authors recommended biosimilars be clearly identifiable, using a unique brand name with the international proprietary name, and the lot number be provided.

Following years of study on the issue including findings from the first 20-country survey, in 2014 the WHO’s INN Expert Group in fact proposed a voluntary naming standard which would address these concerns.

Under the proposed system, all biologics sharing an INN be assigned a unique four-letter suffix called a “biological qualifier” or BQ, tied to the marketing authorization holder (MAH). Advantages of such a system include increased transparency, decreased likelihood of inadvertent or inappropriate substitution, improved traceability including more accurate attribution of adverse events to the correct product, and increased manufacturer accountability for their products.

While initially recieving strong support from many national regulatory authorities including the FDA, Health Canada, and Australia’s Therapeutic Goods Administration (TGA), the BQ proposal has not yet been implemented. In the absence of WHO making this system available, in 2015 the FDA adopted its own BQ-like suffix system.

In 2018, Australia adopted the European approach citing lack of WHO progress on implementation of the BQ system. Similarly, until 2019 Health Canada was in conversations with FDA about harmonizing distinct nomenclature systems regionally, but ultimately went with the brand+INN approach used in Europe, again citing lack of WHO action on distinct naming as a reason. However, both Canada and Australia have expressed their willingness to harmonize with the WHO standard were it to be made available.

Learn more about the BQ proposal here.

Read a summary of the paper’s findings here.

Read the paper here. 
 

FDA Approves 29th Biosimilar, Third for Rituximab
On December 17th, the US Food and Drug Administration (FDA) approved Rianbi (rituximab-arrx). Rianbi (rituximab-arrx) is manufactured by Amgen and the third FDA-approved biosimilar to Genentech’s Rituxan (rituximab). It is the third biosimilar FDA has approved in 2020 and the 29th approved in the past 5 years.

Read more about the successes FDA’s of the biosimilar program here.

Rianbi (rituximab-arrx) is indicated to treat adult patients with non-Hogkin’s lymphoma, chronic lymphocytic leukemia, granulomatosis with polyangiitis and microscopic polyangiitis.

Rianbi (rituximab-arrx) will launch in January 2021. According to the manufacturer, its wholesale acquisition cost (WAC) will be 23.7% lower than the originator, 15.2% lower than Truximab (rituximab-abbs) and comparable to that of Ruxience (rituximab-pvvr). At launch its average sale price (ASP) will be 16.7% lower than the originator.

Learn more about the approval here. 

Read the label/packaging insert for Rianbi (rituximab-arrx) here. 

On December 9th, ASBM Advisory Board Chair Philip Schneider presented virtually to the Saudi Society for Rheumatology. The presentation was carried live to gatherings of rheumatologists in Riyadh, Saudi Arabia; Kuwait City, Kuwait; and Baghdad, Iraq.

Entitled “Lessons from European Biosimilar Markets”, the presentation was based on the whitepaper “Policy recommendations for a sustainable biosimilars market: lessons from Europe” published February 2020 in the GaBI Journal and co-authored by Reilly and Schneider.

The paper examined biosimilar substitution policies across Europe, identifying factors which led to their successful and sustainable biosimilar markets.

The analysis identified six principles the authors refer to as the “Gold Standard”: 

• Policies should be designed to incentivize and reward innovation in all types of biologicals.
• Healthcare financing must take into account societal benefits derived from biological medicines, as well as the unique characteristics of biologicals.
• Procurement practices must provide for multiple suppliers and a minimum term of 12 months.
• Physicians must have autonomy to choose the most appropriate medicine for their patient, including making decisions on switching, which must also be consented to by the patient; no automatic substitution.
• Mandatory brand-name prescribing to avoid unintended switches and a robust pharmacovigilance system to report adverse drug reactions (ADRs).
• Policies with potential to undermine sustainability, such as measures which induce biosimilar uptake or promote preferential treatment, thereby limiting physician choice, should be avoided.

The paper also identified three “Must-Haves” for a sustainable biosimilar market:

• 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.
• 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.
• 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.

Read the whitepaper here. 

On November 19th, the US Food and Drug Administration (FDA) issued new Draft Guidance entitled “Biosimilarity and Interchangeability: Additional Draft Q&As on Biosimilar Development and the BPCI Act”
The document offers insights into how FDA will handle certain aspects of submissions and labeling for interchangeable biosimilars.

These include how an applicant may seek FDA review for licensure for an interchangeable biosimilar, and how a 351(a) BLA holder should proceed if it seeks licensure of its biological product under section 351(k) as biosimilar to or interchangeable with another biological product licensed under section 351(a) (a “reference product”). In addition, the document discusses recommendations for labeling of interchangeable biosimilars.

When finalized, FDA will move the questions and answers from the draft guidance to its companion final questions and answers guidance on biosimilar development.
Comments will be accepted on the Draft Guidance until January 19, 2021.

Read the Draft Guidance here. 
Comments may be submitted here. 

Missed last month’s ASBM Newsletter? Read it Here.

ASCO Gastrointestinal Cancers Symposium

Virtual – January 15-17, 2021

DIA Latin America Regulatory Conference

Virtual – February 22-23, 2021

World Biosimilar Congress USA 2021

Virtual – March 29-31, 2021

WHO 72nd INN Consultation

Geneva, Switzerland – April 12, 2021

The paper examined biosimilar substitution policies across Europe, looking for commonalities which led to successful and sustainable biosimilar markets. The analysis identified six principles the authors refer to as the “Gold Standard”:

• Policies should be designed to incentivize and reward innovation in all types of biologicals.
• Healthcare financing must take into account societal benefits derived from biological medicines, as well as the unique characteristics of biologicals.
• Procurement practices must provide for multiple suppliers and a minimum term of 12 months.
• Physicians must have autonomy to choose the most appropriate medicine for their patient, including making decisions on switching, which must also be consented to by the patient; no automatic substitution.
• Mandatory brand-name prescribing to avoid unintended switches and a robust pharmacovigilance system to report adverse drug reactions (ADRs).
• Policies with potential to undermine sustainability, such as measures which induce biosimilar uptake or promote preferential treatment, thereby limiting physician choice, should be avoided.

The paper also identified three “Must-Haves” for a sustainable biosimilar market:

• 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.
• 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.
• 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.

Read the whitepaper here. 

FDA Issues Draft Guidance on Biosimilarity and Interchangeability

On November 19th, the US Food and Drug Administration (FDA) issued new Draft Guidance entitled “Biosimilarity and Interchangeability: Additional Draft Q&As on Biosimilar Development and the BPCI Act”
The document offers insights into how FDA will handle certain aspects of submissions and labeling for interchangeable biosimilars.

These include how an applicant may seek FDA review for licensure for an interchangeable biosimilar, and how a 351(a) BLA holder should proceed if it seeks licensure of its biological product under section 351(k) as biosimilar to or interchangeable with another biological product licensed under section 351(a) (a “reference product”). In addition, the document discusses recommendations for labeling of interchangeable biosimilars.

When finalized, FDA will move the questions and answers from the draft guidance to its companion final questions and answers guidance on biosimilar development.
Comments will be accepted on the Draft Guidance until January 19, 2021.

Read the Draft Guidance here.
Comments may be submitted here. 
 

On November 18, the Biologic Prescribers Collaborative, along with the Institute for Patient Access and the Alliance for Patient Access hosted its fifth annual National Policy & Virtual Summit on Biologics. As part of the Summit, ASBM Chair Madelaine Feldman, MD, FACR, was interviewed by AfPA’s Gavin Clingham about ASBM’s new whitepaper “US Biosimilars Market on Pace with Europe”; published in GaBI Journal. The paper is co-authored by Dr. Feldman along with ASBM’s Executive Director Michael Reilly.

As Dr. Feldman explains, the paper demonstrates FDA is moving at approximately the same pace as EMA based on the number of approvals at the same time after implementation of its regulatory pathway:

• As of September 2020, approximately 10 years after implementation of the biosimilar approval pathway, 28 biosimilars have been approved by FDA, with 18 of those approvals granted in the last 2 years. For comparison, in the 10-year time period following the creation of Europe’s biosimilar regulatory pathway, EMA approved just 13 biosimilar products (some of which were marketed under several different brands)
• Currently, there are 46 biosimilars approved in Europe; however, these estimates fall to 35 when products approved in the US as follow on biologicals via the 505(b)(2) pathway, e.g. somatropin, insulin, teriparatide, or abbreviated new drug application (ANDA) are excluded. Furthermore, Europe’s filgrastim biosimilar Tevagrastim®/Ratiograstim® was approved as Granix® (tbo-filgrastim) in the US via a Biologic License Application (BLA) prior to the implementation of a biosimilars approval pathway and is not included in the US biosimilar count.

In addition, US biosimilars have gained significant share in the majority of therapeutic areas in which they have been introduced, ranging on average from 20% to 25% within the first year of launch, with some projected to reach greater than 50% within the first 2 years:

• As expected, first-to-market biosimilars tend to capture a greater portion of the segment compared to later entrants. Filgrastim biosimilars have been on the market the longest at 5 years and have achieved a 72% share.
• Bevacizumab and trastuzumab biosimilars, launched in 2019-2020 have approximately 40% share.
• Rituximab and infliximab have had the most limited adoption, with approximately 20% market share.

Watch Dr. Feldman’s interview here.

Read the full whitepaper here. 

View the entire National Policy & Virtual Summit on Biologics here.

On November 15th, ASBM submitted comments on the United Kingdom’s Medicines and Healthcare products Regulatory Agency’s (MHRA’s) guidance intended to help developers of biosimilars more clearly understand the requirements for biosimilar products in the UK.

• UK reference products
• the lack of requirement for in vivo studies in animals
• the changes in the requirement for a comparative efficacy trial in most cases

Among the elements addressed in ASBM’s comments was the language surrounding the need for comparative efficacy trials. The MHRA Guidance stated “In most cases, a comparative efficacy trial is not considered necessary.” From ASBM’s comments:
Given that it is not possible to create a structurally identical copy of a reference product, ASBM believes that a comparative clinical study will generally be warranted to rule out the existence of any clinically meaningful differences between the proposed biosimilar and the reference product. While there are cases in which a comparative efficacy trial is not warranted (ie, when structure, physicochemical characteristics, and biologic activity can be well characterized and clinically relevant PD parameters are available), we believe this will be a minority of biosimilar products and recommend the language in the guidelines be amended to state,

“In some cases, a comparative efficacy trial is not considered necessary”.

With regard to biosimilar substitution practices, however, MHRA’s guidance states:

The decision rests with the prescriber in consultation with the patient, who needs to be aware of the brand name of the product received. Substitution at the pharmacy level without consulting the prescriber is not permitted for biological medicines, including biosimilars.
This provision is constent with subsitution practices throughout nearly every European country, and with ASBM’s position. From ASBM’s comments:

Around the world, substitution decisions are largely handled at the local government level; in the US, the decision of whether a biosimilar is substitutable is made at the state level. In Canada, this decision is made at the provincial level, while within the European Union, the decision is made by individual Member States. ASBM believes that patients and their physician should remain in control of their treatment decisions, rather than an insurer, government, pharmacy, or other third party. We support MHRA’s position on the prohibition of automatic substitution.

On November 5th and 6th, ASBM exhibited virtually at American College of Rheumatology (ACR) Convergence 2020. The virtual conference took place ran from November 5 – 9, with dedicated exhibit hours on November 5th and 6th. More than 15,000 attendees from 106 countries attended the meeting.

ASBM’s virtual booth promoted recent ASBM whitepapers and posters, including a poster presented at the June 2020 EULAR E-Congress which drew from ASBM’s 2019 survey of rheumatologists across six Western European countries. Among the issues the survey covered are prescriber attitudes toward prescribing biosimilars to new patients, switching patients to biosimilars, and toward third party-initiated substitutions for nonmedical reasons. Key findings included:

• Rheumatologists were the most with familiar with biosimilars among the practice areas surveyed (99% familiar).
• They had a higher than average comfort level prescribing biosimilars to new patients: 60% of rheumatologists were “very comfortable” doing so, while the average figure across the ten specialties surveyed was 34%.
• Rheumatologists were also the least comfortable with a third party switching their patient for non-medical reasons (e.g. cost): 49% were “very uncomfortable” with this practice, compared to an average of 29% across all specialties.

Read more about ACR Convergence 2020 here. 

View the EULAR 2020 poster here. 

Missed last month’s ASBM Newsletter?

Read it Here.

Saudi Gastroenterology Association Conference

Virtual – December 9, 2020

DIA Latin America Regulatory Conference

Virtual – February 22-23, 2021

World Biosimilar Congress USA 2021

Virtual – March 29-31, 2021