Posts – Safe Biologics

Medicare Price “Negotiations” Will Jeopardize Patient Access to New Medicines, Result in Worse Health Outcomes

September 11, 2023

The Centers for Medicare & Medicaid Services (CMS) recently announced the first 10 drugs selected under its Medicare drug price “negotiation” plan, authorized by the Inflation Reduction Act (IRA) signed in to law last year. Over the next 4 years, Medicare will set prices for up to 60 drugs covered under Medicare Part D and Part B. This shortsighted move won’t control costs and threatens to limit patient access to new medicines, ultimately resulting in worse health outcomes for U.S. patients, warns ASBM.

IRA Changes Break a Successful Program
Michael Reilly, ASBM Executive Director and former Associate Deputy Secretary in the U.S. Department of Health and Human Services, worked on the development and implementation of the Part D prescription drug benefit during his six years in the Secretary’s Office. While proponents of government price-setting in Medicare claim this will create savings and lower costs, Reilly disagrees:

“Part D was designed following two decades of experience seeing government price-setting fail to control Medicare costs for services and healthcare provider rates. To avoid this happening with the new prescription drug benefit, we created a new model. Contrary to what many believe, under Part D, drug price negotiations do occur- they are conducted by pharmacy benefit managers (PBMs), and the law specifically forbid government interference in price-setting or formulary selection. As we intended, this approach has been incredibly successful in controlling costs: the Congressional Budget Office projected drug spending between 2004-2013 to be $770 billion; actual expenses were 45% lower- at $421 billion. It has a 90% approval rating among beneficiaries^[1], premiums have held steady around $32/month since 2006, and it holds the distinction of being the only major federal program to ever come in under budget.”

A Better Reform: Ensuring Savings Are Passed Onto Patients
While price-setting proponents say beneficiaries will start to see lower drug prices beginning in 2026, there’s no evidence that this is true, and there are better ways to lower out-of-pocket costs- and much faster, Reilly explains. “Part D has been hugely successful in lowering costs- but these savings are not always being passed on to the patient by the PBMs. Thankfully, there is a broad bipartisan effort underway in Congress to rectify this and provide immediate relief for patients- this year, not in 2026.” No fewer than eight bills have been introduced or advanced out of committee this session, with bipartisan support, to address PBM rebate and pricing policies that result in higher drug prices for patients.

The Consequences of European-style Drug Price-Setting Policies

Not only will it fail to control costs, imposing European-style price controls on Medicare Part D will spell disaster for American patients in the coming years. Reilly remarks, “The U.S. leads the world in drug innovation and patient access precisely because we’ve rejected the kind of price controls that stifle R&D and delay drug availability in Europe and Asia.” For example:

In the 1970s, European companies developed most new drugs; however, since the implementation of price controls in Europe, U.S. companies now produce 60% of new drugs, while European countries often have percentages in the single digits.^[1]
90% of new cancer drugs are available in the U.S. within the first year, whereas fewer than half are available to cancer patients in Germany, the UK, France, and Canada^[2]
European cancer death rates are 1.7 times higher than in the U.S.^[3]

Reilly describes what European-style health outcomes might look like in the U.S: “Imagine if the U.S. had European cancer death rates. That would translate to an extra 420,000 cancer deaths annually. Europe’s drug price-setting is simply not a policy worth emulating, and American patients should be aware of its public health consequences.”

ASBM Leading Education Efforts
ASBM has submitted comments to CMS critical of the policy and is conducting an educational campaign about the policy’s harmful effects. On July 26^th, ASBM hosted a webinar with the Generics and Biosimilars Initiative (GaBI) to examine the price-setting policy’s impact on drug development and reduced patient access to new medicines. The event featured three former government officials who were instrumental in the development of Medicare Part D’s prescription drug benefit; as well as experts from the fields of cancer drug research and patient advocacy, each of whom voiced their strong concerns with the policy individually and in a panel discussion.

ASBM also maintains an educational microsite for the patient community at IRAPatientInfo.org

The Alliance for Safe Biologic Medicines (ASBM) is a diverse group of stakeholders that includes physicians, pharmacists, patient advocates, researchers, and biopharmaceutical manufacturers. Since 2010, ASBM has worked closely with regulators worldwide as they develop and implement health policies, to ensure that these reflect the best interests of patients.

^[1] “Europe negotiates a poor vaccine rollout”; Forbes, April 2021

^[2] IQVIA Analytics, FDA, EMA, PMDA, TGA, & Health Canada data, April 2021.

^[3] “Democrat plan on drug costs will stifle innovation”, San Antonio Express-News, May 12, 2021

^{^[1]} https://www.usatoday.com/story/onpolitics/2012/10/03/poll-medicare-prescription-drug-program-popular/1609995/

Analysis Finds Misinformation About Interchangeable Biosimilars Undermining US Health Policy, Physician Confidence, and Patient Health

July 16, 2024

WASHINGTON, July 16, 2024 – The Alliance for Safe Biologic Medicines (ASBM) announces the publication of a paper underscoring the critical role of the FDA’s interchangeable biosimilar data requirements in maintaining the safety and efficacy of biosimilar substitutions. Titled “Misinformation about interchangeable biosimilars undermines US health policy, physician confidence, and patient health,” the paper discusses the successes of the FDA’s data-driven approach in building physician and patient confidence in biosimilars and provides an analysis of the potential risks associated with weakening these proven standards.

In the U.S., as in most advanced nations, a prescribing physician may substitute any biosimilar for its reference product. However, substitution of biosimilars at the pharmacy level is controversial, opposed by majorities of physicians worldwide, and banned in many countries including most of Western Europe. In the U.S., only biosimilars deemed “interchangeable” by the FDA may be substituted by a pharmacist. Thirteen of the 53 approved biosimilars have earned that designation by providing additional data to the FDA demonstrating no loss of safety or efficacy even following multiple switches between a reference biologic and the biosimilar. This data may or may not include a switching study; several interchangeables have been approved without them.

ASBM Chairman and paper co-author Ralph McKibbin, MD: “All FDA-approved biosimilars are safe and effective, but treatment plans are not one-size-fits-all. Each is uniquely tailored, and patients frequently try several products before finding one that best stabilizes their condition. Physicians need to be confident that a substitution by a pharmacy or insurance company won’t disrupt the patient’s treatment stability. The interchangeable standard’s data requirements provide that assurance.”

ASBM Executive Director and paper co-author Michael S. Reilly: “While 89% of U.S. physicians are confident in the safety and efficacy of biosimilars, 69% believe only the physician and patient should determine which biologic to use, not a third-party such as a pharmacy or insurance company. These views are shared by physicians worldwide. But when a biosimilar carries an interchangeable designation, the majority (58%) of U.S. physicians are more comfortable with a pharmacy-level substitution because of the additional safety and efficacy data. The FDA’s standards are working, and any effort to lower them could compromise the progress we’ve made in building physician and patient confidence in biosimilars.”

The publication of this paper comes at a critical time as the FDA seeks public comment on recent draft guidance that proposes to lower the data requirements for demonstrating interchangeability, and the U.S. Senate is considering a bill that would deem all biosimilars interchangeable and severely restrict the FDA’s ability to ask for additional data. The paper critically examines the recent meta-analysis often cited by proponents of lowering these standards. Focusing on safety but neglecting efficacy impacts and extrapolating multi-switch safety from mostly single-switch studies, McKibbin and Reilly argue the data do not support the proposed policy change.

Reilly attributes the push to weaken the current standard to widespread misconceptions and misinformation about interchangeability: “Some incorrectly believe switching studies are mandated by the FDA for a biosimilar to be deemed interchangeable, when in fact the FDA has flexibility and approved several without switching studies. Others confuse European Medicines Agency’s definition of “interchangeable” (meaning physician-substitutable) with the U.S. definition (meaning pharmacist-substitutable) and incorrectly believe the proposed policy change would bring the U.S. in line with Europe. In reality, pharmacy substitution of biosimilars is rare in Europe and frequently banned by EU member states. Accurate information and education are critical to avoid policy missteps that will undermine the FDA’s success in building physician confidence in biosimilars and protecting patients’ health.”

The full paper can be accessed in the latest issue of the Journal of the Generics and Biosimilars Initiative (GaBI Journal) here.

April 2024 Newsletter

May 21, 2024

ASBM’s Michael Reilly: Preserve the US Interchangeable Standard that Has Helped Drive Physician and Patient Confidence in Biosimilars
In an April interview with EndpointsNews, an FDA official called on Congress to eliminate the distinction between biosimilars (which can be prescribed in place of their reference products by a physician) and “interchangeable” biosimilars, which can be substituted by pharmacists the way generics are. Doing so would undermine physician confidence in biosimilars and jeopardize treatment stability for many patients, according to ASBM’s Executive Director, Michael Reilly in a r esponse published in GaBI Journal. The FDA comments echo language in the Administration’s FY2025 HHS Budget which alleges the interchangeable standard creates “confusion” among healthcare providers. On the contrary, Reilly explains, it creates confidence: The interchangeable standard, through its additional data requirements, reassures physicians that switching won’t reduce treatment efficacy: 59% are more comfortable with an interchangeable being substituted at the pharmacy. “Biosimilars, while safe and effective, aren’t generics and shouldn’t be treated as such. 50 U.S. state legislatures were not confused when they passed legislation limiting pharmacy substitution only to interchangeable biosimilars”, says Reilly. “These were supported by state medical societies conditional on these assurances. Breaking this commitment to physicians would be an unconscionable bait-and-switch by policymakers.” Moreover, while the Administration claims eliminating the distinction would bring the U.S. more into line with European substitution practices, in fact the opposite is true: The EMA does not weigh in on pharmacy substitution of biosimilars; this is reserved for member states and nearly every Western European country has decided (like U.S. states) that this is not acceptable. A 2019 survey revealed a strong majority (73%) of Europe’s physicians, like their U.S. counterparts, oppose third-party biosimilar substitution. Finally, biosimilar uptake is largely determined by insurer and PBM formulary design, not a biosimilar’s interchangeable designation, Reilly explains. “CVS Caremark, which controls 34% of the market, recently dropped the reference adalimumab in favor of its own co-branded biosimilar version. Within a week, adalimumab biosimilar market share rose from 5% to 36%, lack of automatic-substitutability by a pharmacist posed no obstacle”. Cigna, a PBM controlling 24% of the U.S. market, has announced plans to make a similar move in June. “The interchangeable biosimilar standard is working as intended: building physician confidence through data and providing a biosimilar option physicians can be certain will not jeopardize the treatment stability of a patient for whom maintaining it is a critical concern.There are several promising bipartisan legislative efforts underway in Congress bring more transparency to PBM formulary design and rebate practices. These represent a far more productive -and medically appropriate- target for reform efforts for those seeking to boost biosimilar uptake.” Read the article in GaBI Journal here.

ASBM Comments Urge EMA Not to Abandon Clinical Data in Biosimilar Approvals
On April 30, ASBM submitted comments to the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) as part of a public consultation periodon the Agency’s “Concept paper for the development of a Reflection Paper on a tailored clinical approach in Biosimilar development”. The document expresses the EMA’s intent to streamline biosimilar development by re-evaluating the role of clinical safety and efficacy data. Read the concept paper here. Read ASBM’s comments here.

FDA Celebrates 50th Biosimilar Approval On April 25, the FDA approved its 50^thbiosimilar. Its announcement was accompanied by a statement touting the many successes of the U.S. biosimilar program since the first approval in 2015, including savings to the U.S. health system and increased access to biologic treatments for patients. From the FDA statement: According to a 2023 report by the Association of Accessible Medicines, FDA-approved biosimilars have saved the health care system $23.6 billion since the first biosimilar product was approved in 2015. Collectively, patients have used biosimilars for almost 700 million days of therapy, 344 million days of which patients received care they otherwise may not have received. The impact and potential of biosimilars are significant not only in terms of savings to the health care system, but also for health equity and helping improve patients’ access to medications that were previously beyond their reach.
Read the FDA’s statement on this milestone here.

ASBM Chairman Urges State and Federal Lawmakers to Help Ensure Patient Access, Treatment Choice In early April ASBM Chairman Ralph McKibbin joined with the Pennsylvania Nonmedical Switching Coalition to meet with members of the Pennsylvania House of Representatives Insurance committee to answer questions and advocate regarding the impact of nonmedical switching on patients in the state. PA State Senate bill 348 amends the Unfair Insurance Practices Act to prevent nonmedical switching and a House companion bill is pending. Dr. McKibbin also participated as part of the American College of Gastroenterology Board of Governors in their legislative action session April 17-19 in Washington, DC. Meetings were held with both U.S. Senate and House members to advocate for patient access to care. During the educational session, Dr. McKibbin presented on the importance of the leadership provided by stakeholder organizations.

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

UPCOMING EVENTS ASCO Annual MeetingChicago, IL – May 31-June 4, 2024 BIO International Meeting
San Diego, CA – June 3-6, 2024 DIA Global Annual Meeting
San Diego, CA – June 16-20, 2024 ACR Convergence 2024
Washington, DC – November 14-19, 2024

March 2024 Newsletter

May 10, 2024

Biden Administration HHS Budget Would Permit Third-Party Substitution of All Biosimilars
On March 11th, the Biden Administration released its FY25 HHS Budget. In response, ASBM Executive Director Michael Reilly published a blog post sharing his concerns with the Administration’s proposal to permit widespread automatic (pharmacy-level) substitution of all biosimilars in place of their reference products; without physician approval or FDA evaluation as current law requires. From the post: The HHS Budget in Brief document describes the policy objective simply enough: “Permit Biosimilar Substitution without Prior FDA Determination of Interchangeability” and clarifies that this means “deem all approved biosimilars to be interchangeable with their respective reference products”.
It justifies the policy by claiming “this change makes the U.S. biosimilar program more consistent with the approach adopted by other major regulatory jurisdictions such as the European Union where biosimilars are interchangeable with their respective reference products upon approval.”
In the U.S. and Europe alike, prescribers can already substitute any biosimilar for its reference product. What is at stake and where the two regions differ somewhat in policy is when and how pharmacies can substitute biosimilars. The confusion stems from the fact that the term “interchangeable” has different meanings in the U.S. and Europe:
In Europe,“Interchangeable” means prescriber-substitutable:
The European Medicines Agency (EMA) has stated all biosimilars it approves are “interchangeable” in that they “may be prescribed interchangeably” and that this does not refer to pharmacy substitution: “Member States will continue to decide…whether automatic substitution is allowed at the pharmacy level.” In the U.S., however, “interchangeable” refers to a biosimilar which under state law may be substituted at the pharmacy level without physician approval because its manufacturer has provided additional data to the FDA demonstrating a patient can be switched between the biosimilar and reference product and expect the same result. Currently there are 10 biosimilars that can be substituted by U.S. pharmacies in this manner, with more on the way. 69% of US physicians surveyed consider it “very important or critical” that patients and physicians decide the most suitable biologic to use- be it the reference product or one of the biosimilars to that product. However 59% of physicians are more comfortable with an interchangeable being substituted in place of the prescribed originator product. The Biden budget proposal would undermine this hard-won confidence by eliminating the FDA’s science-based data requirements for permitting pharmacy-substitution of biosimilars, and declaring by fiat that all biosimilars substitutable by the pharmacy, despite the opposition from U.S. physicians. And it does so based at least in part on a serious misunderstanding of what the health systems of other advanced countries permit. Read more here. View ASBM’s educational fact sheet “Interchangeability: US vs EU” here.

Biden’s SOTU: 500 Drugs To Be Subject to Medicare Drug Price Controls
On March 7th, President Biden gave his State of the Union address to Congress, wherein he laid out upcoming policy priorities for a potential second term. Among these was an expansion of the Medicare Drug price setting provisions passed in 2022 as part of the Inflation Reduction Act (IRA). Biden seeks to dramatically increase the number of drugs subject to Medicare price negotiations, said President Biden in the address:This year Medicare is negotiating lower prices for some of the costliest drugs on the market that treat everything from heart disease to arthritis. Now it’s time to go further and give Medicare the power to negotiate lower prices for 500 drugs over the next decade. CMS is currently working to set prices for 10 drugs, with the final prices set to be announced by Sept. 1 and go into effect in 2026. Without a change, the number of eligible drugs will increase to 15 in 2027 and 2028 and to 20 every year thereafter. ASBM recently hosted a webinar in which former government health officials who worked on Medicare Part D, the program’s prescription drug benefit, discuss the harmful impacts of the IRA’s price setting policies. Read more about how IRA Medicare Drug price setting will negatively affect patient access to new medicines at ASBM’s microsite IRAPatientInfo.org.

ASBM Presents at World Health Organization’s 78th INN Consultation
On March 19th, ASBM presented to the World Health Organization International Nonpropretary Names (INN) Expert Group at the 78th Consultation on International Non-proprietary Names for Pharmaceutical Substances (INN), held in Geneva, Switzerland on October 18th, 2023. ASBM was represented at the session by Executive Director Michael Reilly, Esq., and Advisory Board Chair Philip Schneider, MS, FASHP. The proceedings of the INN Consultation are bound by confidentiality pending the publication of the Executive Summary by the WHO. However, the recently-released Executive Summary from the 77th INN Consulation (held October 19, 2023) lays out the benefits for a distinct nomenclature standard, and highlights the ongoing support for such a standard, both from ASBM as well as from regulators. From the Executive Summary: The ASBM has supported the INN Group’s Biological Qualifier (BQ) scheme since its inception in 2012, and since then has doggedly presented data on the importance of a BQ to enhancing patient safety and pharmacovigilance (PV). However, they have also learned that WHO moves slowly, has many global health issues to deal with and has many stakeholders. Almost 10 years after the inception of the BQ, with no further action ensuing, a WHO report in 2021 highlighted that a lack of consistency in naming biosimilars had caused concern in prescribing, prescription mix-ups, unintended switching and traceability, and concluded that naming and labelling was important for product identification, PV and prescribing. When the BQ was first proposed, ASBM noted that several global regulatory agencies supported the scheme, including the US FDA which eventually adopted its own not dissimilar system comprising a random four-letter suffix. Other supporting agencies await the WHO implementing a global system. In the EU, the EMA has stated that it does not need a BQ as it has an alternative system in place but recognises the value of a unified system. Several arguments have been raised by stakeholders opposed to a BQ; however, in each case these have proven to be unfounded. For example, it had been stated that distinguishable names may imply inferior products, but this has not been the case in USA. In addition, surveys have shown that a supposed lack of support by physicians and global regulators was incorrect. Over these years also, the ASBM has surveyed and met with many global regulators and physicians and the vast majority support distinct nomenclature. The lack of action with the BQ has forced many regulators, either assigning the same non-proprietary name to biosimilars or in some cases to adopt their own system. However, most of them are willing to support a WHO system if it is implemented. The ASBM made a proposal to quantify support for the BQ. . It acknowledged support for a BQ system and with the debate having continued for 10 years now it strongly encourage the WHO to take a leadership role. Dr Balocco noted that the department had a new ADG and that WHO was soon to have a new Director-General. The WHO has been asked to work on a Global Substance Identifier (GSID) and there may be an opportunity to bring in the BQ as part of this. The INN Programme is in fact ready to implement a BQ. Dr Balocco expressed hope that a decision would be taken soon as the INN by itself is not sufficient for PV. Read the full Executive Summary of the 77th INN Consultation here.

Reminder: EMA Seeks Public Comment on Re-evaluating the Need for Clinical Safety and Efficacy Data in Biosimilar Development; Comments Due April 30
On January 25, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) released a document entitled “Concept paper for the development of a Reflection Paper on a tailored clinical approach in Biosimilar development”. The document expresses the EMA’s intent to streamline biosimilar development by re-evaluating the role of clinical safety and efficacy data; it also announces a three-month public consultation period running from February 1 to April 30, 2024. From the announcement: Constantly striving for scientifically sound yet efficient processes, the Biosimilar regulatory framework has constantly been evolving towards increasingly tailored developments, starting from smaller and “simpler” biologics, such as recombinant Granulocyte-Colony Stimulating Factor (rG-CSF), insulins or somatropin where the need for comparative clinical efficacy trials is in general not required any more. With growing knowledge and the increasing possibilities of analytical and functional characterisation, revisiting the need for clinical efficacy trials for biosimilars (especially recombinant proteins and mAbs) is considered the next important step in order to keep the Biosimilar pathway attractive for developers and, at the same time, guarantee future access to safe and efficacious biologics for European patients. The CHMP recognizes that there may be the potential to waive certain clinical data requirements even for complex biosimilars such as mAbs based on solid evidence of quality comparability. When the biosimilar demonstrates a high degree of similarity to the RMP at the analytical and functional level, it may be possible to justify the omission of dedicated CES. Comments may be submitted here until April 30, 2024. Read the concept paper here.

How IRA Price Setting Disccourages Biosimilar Development
In a recent op-ed in USA Today, Rutgers University professor Sandip Shah, argues that the price-setting provisions of the Inflation Reduction Act (IRA) are unintentionally disincentivizing biosimilar development:The IRA permits Medicare officials to impose price controls on certain brand-name drugs, including many biologics. But the government does not have to reveal which medicines will be subject to price caps until just two years prior to the lower prices taking effect.As a result, a firm could hypothetically spend nearly a decade and hundreds of millions of dollars developing a biosimilar — only to find out that the original brand-name biologic will suddenly be much cheaper, courtesy of government price controls. In such a scenario, the biosimilar developer would be unable to gain enough market share to break even on its R&D investments, let alone earn a modest return.Lawmakers can restore incentives for biosimilar drug makers by automatically — and permanently — exempting from price controls any biologic for which there is a biosimilar competitor in development.Unless and until that happens, the legacy of the Inflation Reduction Act will be reduced access to low-cost biosimilars — ultimately leading to higher drug spending. Read the op-ed here.

FDA Approves Three Interchangeable Biosimilars in First Quarter of 2024
During the first quarter of 2024, the FDA approved three additional interchangeable biosimilars, bringing the total number of approved interchangeable biosimilars to 10, and the total number of biosimilars to 48. On February 24th, the FDA approved Simlandi (adalimumab-ryvk), a biosimilar to Humira (adalimumab). The TNF alpha inhibitor was approved for treating plaque psoriasis, Crohn’s disease, ulcerative colitis, rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, hidradenitis suppurativa, and uveitis. On March 5th the FDA approved two interchangeable biosimilars: Jubbonti (denosumab-bbdz), interchangeable for Prolia (denosumab), and Wyost (denosumab-bbdz), interchangeable for Xgeva (denosumab). Jubbonti was approved for increasing bone mass in men and women and breast cancer, for osteoporosis (induced by glucocorticoid treatment or otherwise) in men and women, and for preventing fracture in post-menopausal women with osteoporosis. Wyost was approved for treating patients with multiple myeloma and solid tumor bone metastases, giant cell bone tumors, and treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy. Read more about the approvals here and here.

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

ASBM’s Michael Reilly: Preserve the US Interchangeable Standard that Has Helped Drive Physician and Patient Confidence in Biosimilars

May 10, 2024

In an April interview with EndpointsNews, an FDA official called on Congress to eliminate the distinction between biosimilars (which can be prescribed in place of their reference products by a physician) and “interchangeable” biosimilars, which can be substituted by pharmacists the way generics are. Doing so would undermine physician confidence in biosimilars and jeopardize treatment stability for many patients, according to ASBM’s Executive Director, Michael Reilly in a r esponse published in GaBI Journal. The FDA comments echo language in the Administration’s FY2025 HHS Budget which alleges the interchangeable standard creates “confusion” among healthcare providers. On the contrary, Reilly explains, it creates confidence:

The interchangeable standard, through its additional data requirements, reassures physicians that switching won’t reduce treatment efficacy: 59% are more comfortable with an interchangeable being substituted at the pharmacy. “Biosimilars, while safe and effective, aren’t generics and shouldn’t be treated as such. 50 U.S. state legislatures were not confused when they passed legislation limiting pharmacy substitution only to interchangeable biosimilars”, says Reilly. “These were supported by state medical societies conditional on these assurances. Breaking this commitment to physicians would be an unconscionable bait-and-switch by policymakers.”

Moreover, while the Administration claims eliminating the distinction would bring the U.S. more into line with European substitution practices, in fact the opposite is true: The EMA does not weigh in on pharmacy substitution of biosimilars; this is reserved for member states and nearly every Western European country has decided (like U.S. states) that this is not acceptable.

A 2019 survey revealed a strong majority (73%) of Europe’s physicians, like their U.S. counterparts, oppose third-party biosimilar substitution. Finally, biosimilar uptake is largely determined by insurer and PBM formulary design, not a biosimilar’s interchangeable designation, Reilly explains. “CVS Caremark, which controls 34% of the market, recently dropped the reference adalimumab in favor of its own co-branded biosimilar version. Within a week, adalimumab biosimilar market share rose from 5% to 36%, lack of automatic-substitutability by a pharmacist posed no obstacle”. Cigna, a PBM controlling 24% of the U.S. market, has announced plans to make a similar move in June. “The interchangeable biosimilar standard is working as intended: building physician confidence through data and providing a biosimilar option physicians can be certain will not jeopardize the treatment stability of a patient for whom maintaining it is a critical concern.

There are several promising bipartisan legislative efforts underway in Congress bring more transparency to PBM formulary design and rebate practices. These represent a far more productive -and medically appropriate- target for reform efforts for those seeking to boost biosimilar uptake.”

Read the article in GaBI Journal here.

ASBM Chairman Urges State and Federal Lawmakers to Help Ensure Patient Access, Treatment Choice

April 30, 2024

In early April ASBM Chairman Ralph McKibbin joined with the Pennsylvania Nonmedical Switching Coalition to meet with members of the Pennsylvania House of Representatives Insurance committee to answer questions and advocate regarding the impact of nonmedical switching on patients in the state. PA State Senate bill 348 amends the Unfair Insurance Practices Act to prevent nonmedical switching and a House companion bill is pending. Dr. McKibbin also participated as part of the American College of Gastroenterology Board of Governors in their legislative action session April 17-19 in Washington, DC. Meetings were held with both U.S. Senate and House members to advocate for patient access to care. During the educational session, Dr. McKibbin presented on the importance of the leadership provided by stakeholder organizations.

ASBM Comments Urge EMA Not to Abandon Clinical Data in Biosimilar Approvals

April 30, 2024

On April 30, ASBM submitted comments to the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) as part of a public consultation period on the Agency’s “Concept paper for the development of a Reflection Paper on a tailored clinical approach in Biosimilar development”. The document expresses the EMA’s intent to streamline biosimilar development by reevaluating the role of clinical safety and efficacy data. From ASBM’s comments:

We believe that clinical data, including comparative effectiveness studies
(CES), have played a critical role in building physician and patient
confidence in biosimilars and should continue to be required for complex
biosimilars such as monoclonal antibodies. CES are critical because they
provide direct evidence of how a biosimilar works in humans. They
demonstrate real, not merely theoretical safety and efficacy in a wide
variety of patients. CES also helps address individual patient variability.
Replacing the current, highly successful approval standards could
undermine this success, potentially causing physicians to be less accepting
of newer biosimilars approved under the lower standard, and instead
preferentially prescribe the reference product or earlier biosimilars
approved under the previous, more robust standards.

Similarly, the change may have unforeseen negative effects on patient
confidence in biosimilars. Knowing that a biosimilar has undergone
thorough clinical test-ing to demonstrate its safety and effectiveness can be
reassuring for patients, especially those switching from a well-established
biologic therapy. It is conceivable that a mass nocebo effect could be
produced across many patient populations by these regulatory changes,
stemming from patient uncertainty over reduced clinical testing
requirements and lowered approval standards driven by cost-cutting and
desire for speedier approval.

Read the concept paper here.

Read ASBM’s comments here.

February 2024 Newsletter

April 12, 2024

ASBM Joins ICAN, other Patient Advocacy Organizations to Oppose Government Use of “March In Rights” In February, ASBM joined 33 other patient advocacy organizations led by the International Cancer Advocacy Network (ICAN) in a letter to U.S. Congressional leadership, urging them to oppose the use of “march-in rights” to break pharmaceutical patents for drugs developed with federal funds. In December, the U.S. Department of Commerce’s National Institute of Standards and Technology (NIST) released for public comment its Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights, a tool to help agencies evaluate when it might be appropriate to require licensing of a patent developed with federal funding. From the letter: On behalf of the patients we represent who are fighting lethal diseases, rare diseases, and chronic conditions, the 34 groups below are writing to express our concern regarding the National Institute of Standards and Technology proposed guidance, Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights. The proposal seeks to expand the federal government’s authority to use the Bayh-Dole Act’s march-in rights provision to re license patents based on price objections. While well intended, this jeopardizes the essential purpose and success of the Bayh-Dole Act, and threatens the biopharmaceutical investment and future innovation that we rely on to improve, extend, and save patients’ lives. The United States plays the leading role in the drug discovery that is at the core of the world’s success in making extraordinary progress in reducing mortality from lethal diseases, and alleviating pain and suffering from chronic conditions. This progress was accelerated, in large part, by the bipartisan Bayh-Dole Act framework that incentivized a complementary and collaborative relationship between the public and private sectors in the drug development pipeline. Before the Act, less than five percent of 28,000 patents owned by the federal government had been licensed.1 In other words, innovation that could have benefitted patients sat on the shelf. While we commend President Biden’s goal to make prescription drugs more affordable for American patients, this proposal does not address the underlying cost drivers that result in high out-of-pocket burdens for patients. Dismantling intellectual property protections could, however, initiate a long-term degradation of the drug discovery and development ecosystem in the United States. We are concerned for the potential harm to our patients—and all patients – that could result. Read the full letter here. Read the Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights here.

Reminder: EMA Seeks Public Comment on Re-evaluating the Need for Clinical Safety and Efficacy Data in Biosimilar Development; Comments Due April 30 On January 25, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) released a document entitled “Concept paper for the development of a Reflection Paper on a tailored clinical approach in Biosimilar development”. The document expresses the EMA’s intent to streamline biosimilar development by re-evaluating the role of clinical safety and efficacy data; it also announces a three-month public consultation period running from February 1 to April 30, 2024. From the announcement: Constantly striving for scientifically sound yet efficient processes, the Biosimilar regulatory framework has constantly been evolving towards increasingly tailored developments, starting from smaller and “simpler” biologics, such as recombinant Granulocyte-Colony Stimulating Factor (rG-CSF), insulins or somatropin where the need for comparative clinical efficacy trials is in general not required any more. With growing knowledge and the increasing possibilities of analytical and functional characterisation, revisiting the need for clinical efficacy trials for biosimilars (especially recombinant proteins and mAbs) is considered the next important step in order to keep the Biosimilar pathway attractive for developers and, at the same time, guarantee future access to safe and efficacious biologics for European patients. The CHMP recognizes that there may be the potential to waive certain clinical data requirements even for complex biosimilars such as mAbs based on solid evidence of quality comparability. When the biosimilar demonstrates a high degree of similarity to the RMP at the analytical and functional level, it may be possible to justify the omission of dedicated CES. Comments may be submitted here until April 30, 2024. Read the concept paper here.

Cardinal Health Releases 2024 Biosimilar Report Cardinal Health has released its 2024 Biosimilars Report, which describes the state of the U.S. biosimilar market and identifies major developments over the past year. From the report’s introduction:As of 2023, there were 46 FDA-approved biosimilars, seven of which have interchangeability designations. As more biosimilars enter the marketplace, adoption increases which leads to greater patient access. The expected cost savings of biosimilars continue to be a key area of interest for the government, payers, providers and patients. According to the recent 2023 U.S. Generic and Biosimilar Medicines Savings Report from the Association for Accessible Medicines (AAM), biosimilars generated savings of $9.4 billion in 2023. Since 2015, savings have now climbed to $23.6 billion. This is likely due in part to increased competition bringing the cost of a reference biologic down by 25%.7 This is an exciting product landscape, with new approvals, launches and regulatory action underway.Among the most important developments in biosimilars of 2023, were the launches of no fewer than nine biosimilars for Humira® (adalimumab) in 2023, and the increased role of the interchangeable biosimilar designation in policy discussions:As the top-selling drug in the world with annual sales of $20 billion in 2022, the potential monetary impact of increased market competition cannot be overstated. Of the nine FDA-approved Humira® biosimilars launched in 2023, two have interchangeability designations from the FDA. When a biosimilar has an interchangeability designation, it may be used instead of the biologic reference product by a pharmacist without a new prescription, like the current process for switching a brand-name drug to a generic drug. Per our research, providers prefer products with an interchangeability designation. However, obtaining an interchangeability designation is costly and time-consuming. Accordingly, many manufacturers have not pursued an interchangeability designation for their products. Read the full 2024 Biosimilars Report here.

IRA Price-Setting Adds New Barriers to Curing Rare Diseases On February 19th, The Hill published an op-ed by Eric Dube, president and CEO of Travere Therapeutics, which argues that government price-setting provisions in the Inflation Reduction Act (IRA) discourages development of new drugs to treat rare diseases, and the law must be amended. The IRA’s drug-pricing program allows the federal government to dictate the price Medicare pays for certain brand-name drugs. Recognizing that this policy would likely discourage investment, lawmakers took care to exempt rare disease therapies, also known as “orphan drugs,” from government price setting.
Unfortunately, this exemption only applies to medicines approved for a single disease. Any orphan drug approved for two or more diseases — even if it is a rare disease with no treatment — becomes eligible for government-mandated price setting. It’s this feature of the law that is so destructive.
One common reason companies can decide to pursue rare disease treatments is the promise that a successful drug might prove effective for multiple conditions. For instance, a treatment that successfully defeats one type of rare cancer might work on another type of tumor, or a drug that addresses one autoimmune condition might prove similarly effective on others. When a disease is rare, scientific progress that saves lives often depends on this approach.Drug innovation is a highly risky enterprise, after all. It can cost billions of dollars to develop a new drug, particularly when you take into account the cost of unsuccessful programs. And only about 12 percent of new medicines that enter clinical trials ultimately earn approval.
The possibility that a line of research might produce a treatment for more than one disease helps reduce some of that risk, making it easier to attract investors. So by discouraging work on multiple rare diseases, the IRA creates significant new obstacles to developing innovative new medicines. The author urges Congress to reform the IRA by passing theORPHAN Cures Act, which enjoys broad, bipartisan support. The bill would ensure that all orphan drugs — and not just single-disease therapies — are exempt from the law’s pricing program. Read the op-ed here. Read more about the ORPHAN Cures Act here.

FDA Approves First Interchangeable, High-Concentration, Citrate-Free Adalimumab Biosimilar On February 26, the U.S. FDA announced the approval of the SIMLANDI (adalimumab-ryvk) injection as an interchangeable biosimilar to Humira (adalimumab), for the treatment of adult rheumatoid arthritis, juvenile idiopathic arthritis, adult psoriatic arthritis, adult ankylosing spondylitis, Crohn’s disease, adult ulcerative colitis, adult plaque psoriasis, adult hidradenitis suppurativa and adult uveitis. SIMLANDI is the first high-concentration, citrate-free biosimilar to Humira that has been granted an interchangeability status by the FDA, and will qualify for interchangeable exclusivity for the 40mg/0.4ml injection. While both low-concentration and high-concentration strength biosimilars of Humira are marketed in the U.S. today, nearly 88 percent of U.S. prescriptions for adalimumab are for the high-concentration presentation. An interchangeable biosimilar may be substituted at the pharmacy without consulting the prescriber, much like generic drugs are routinely substituted for brand name drugs. As the only interchangeable adalimumab biosimilar with the high-concentration formulation, SIMLANDI can be substituted for Humira at the pharmacy level, subject to state pharmacy laws. Read more about the approval here.

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

UPCOMING EVENTS WHO 78th INN ConsultationGeneva, Switzerland – March 19, 2024 ASCO Annual MeetingChicago, IL – May 31-June 4, 2024 BIO International Meeting
San Diego, CA – June 3-6, 2024 DIA Global Annual Meeting
San Diego, CA – June 16-20, 2024

Biden Budget Would Allow Automatic Pharmacy Substitution of ALL Biosimilars, Misunderstands US and EU Substitution Policy

April 11, 2024

by Michael Reilly, ASBM Executive Director

The Biden Administration’s FY25 Budget, unveiled on March 11, 2024, takes aim at prescription drug costs but misses the mark and hurts rather than helps patients. Again. (Read my concerns with the Administration’s Medicare Part D price-setting system here).

This latest proposal would loosen the review criteria for some biologics and shift treatment decisions out of the hands of doctors. This proposal is built on a misunderstanding surrounding substitution of medicines and in particular the definition of the word “interchangeable” as it is used with biologic medicines.

These are very different in the US and Europe – similar to how asking for a torch in Europe will get you what we call a flashlight rather than an open flame.

This conceptual error is then used to argue for an inappropropriate expansion of automatic pharmacy-level substitution for all biosimilars- without prior FDA evaluation or physician approval, as current law requires.

The HHS Budget in Brief document describes the policy objective simply enough: “Permit Biosimilar Substitution without Prior FDA Determination of Interchangeability” and clarifies that this means “deem all approved biosimilars to be interchangeable with their respective reference products”.

Skipping over what that means, it justifies the policy by claiming “this change makes the U.S. biosimilar program more consistent with the approach adopted by other major regulatory jurisdictions such as the European Union where biosimilars are interchangeable with their respective reference products upon approval.”

First: in the U.S. and Europe alike, prescribers can already substitute any biosimilar for its reference product. What is at stake and where the two regions differ somewhat in policy is in when and how pharmacies can substitute biosimilars. The confusion stems from the fact that the term “interchangeable” has different meanings in the U.S. and Europe:

In Europe, “Interchangeable” means prescriber-substitutable.
The European Medicines Agency (EMA) has stated1all biosimilars it approves are “interchangeable” in that they “may be prescribed interchangeably” and that this does not refer to pharmacy substitution: “Member States will continue to decide…whether automatic substitution is allowed at the pharmacy level.”

European physicians (73%) strongly oppose substitution of biosimilars by someone other than the doctor for non-medical reasons (e.g. cost).2 Accordingly, this controversial practice is extremely rare in Western Europe and banned in many countries. Some resource-constrained Eastern European countries (e.g Latvia and Estonia) do permit it, however.

In the U.S., “Interchangeable” means pharmacy-substitutable.

In the U.S. “interchangeable” refers to a biosimilar which under state law may be substituted at the pharmacy level without physician approval because its manufacturer has provided additional data to the FDA demonstrating a patient can be switched between the biosimilar and reference product and expect the same result. Currently there are 8 biosimilars that can be substituted by the U.S. pharmacies in this manner, with more on the way.

Like their European counterparts, most U.S. physicians (58%) strongly oppose substitution of biosimilars by someone other than the doctor for non-medical reasons (e.g. cutting costs or increasing insurance company profits ).3 But this isn’t because physicians feel biosimilars are unsafe or ineffective; it’s because treatment plans aren’t one size fits all and many patients try several safe and effective products before they find one that best stabilizes the patient’s condition. Physicians don’t like to change medicines unnecessarily or inappropriately, and they believe the physician and the patient should make this decision, not the pharmacy or the insurance company.

While 89% of U.S. prescribers have high confidence in the safety and efficacy of biosimilars, a majority (58%) oppose third-party switching of a patient’s biologic medicine for non-medical reasons.
69% of US physicians surveyed consider it “very important or critical” that patients and physicians decide the most suitable biologic to use- be it the originator or one of the biosimilars to that product.

However, the extra data currently required to receive an “interchangeable” designation from the FDA increases physician confidence: most physicians (57%) are more comfortable prescribing an interchangeable, and with an interchangeable being substituted in place of the prescribed originator product (59%)3.

The Biden budget proposal would undermine this hard-won confidence by eliminating the FDA’s science-based data requirements for permitting pharmacy-substitution of biosimilars, and declaring by fiat that all biosimilars substitutable by the pharmacy, despite the opposition from U.S. physicians. And it does so based at least in part on a serious misunderstanding of what the health systems of other advanced countries permit.

ASBM Presents at World Health Organization’s 78th INN Consultation

March 21, 2024

On March 19th, ASBM presented to the World Health Organization International Nonpropretary Names (INN) Expert Group at the 78th Consultation on International Non-proprietary Names for Pharmaceutical Substances (INN), held in Geneva, Switzerland on October 18th, 2023. ASBM was represented at the session by Executive Director Michael Reilly, Esq., and Advisory Board Chair Philip Schneider, MS, FASHP. The proceedings of the INN Consultation are bound by confidentiality pending the publication of the Executive Summary by the WHO. However, the recently-released Executive Summary from the 77th INN Consulation (held October 19, 2023) lays out the benefits for a distinct nomenclature standard, and highlights the ongoing support for such a standard, both from ASBM as well as from regulators. From the Executive Summary:

The ASBM has supported the INN Group’s Biological Qualifier (BQ) scheme since its inception in 2012, and since then has doggedly presented data on the importance of a BQ to enhancing patient safety and pharmacovigilance (PV). However, they have also learned that WHO moves slowly, has many global health issues to deal with and has many stakeholders. Almost 10 years after the inception of the BQ, with no further action ensuing, a WHO report in 2021 highlighted that a lack of consistency in naming biosimilars had caused concern in prescribing, prescription mix-ups, unintended switching and traceability, and concluded that naming and labelling was important for product identification, PV and prescribing. When the BQ was first proposed, ASBM noted that several global regulatory agencies supported the scheme, including the US FDA which eventually adopted its own not dissimilar system comprising a random four-letter suffix. Other supporting agencies await the WHO implementing a global system. In the EU, the EMA has stated that it does not need a BQ as it has an alternative system in place but recognises the value of a unified system. Several arguments have been raised by stakeholders opposed to a BQ; however, in each case these have proven to be unfounded. For example, it had been stated that distinguishable names may imply inferior products, but this has not been the case in USA. In addition, surveys have shown that a supposed lack of support by physicians and global regulators was incorrect. Over these years also, the ASBM has surveyed and met with many global regulators and physicians and the vast majority support distinct nomenclature. The lack of action with the BQ has forced many regulators, either assigning the same non-proprietary name to biosimilars or in some cases to adopt their own system. However, most of them are willing to support a WHO system if it is implemented. The ASBM made a proposal to quantify support for the BQ. . It acknowledged support for a BQ system and with the debate having continued for 10 years now it strongly encourage the WHO to take a leadership role. Dr Balocco noted that the department had a new ADG and that WHO was soon to have a new Director-General. The WHO has been asked to work on a Global Substance Identifier (GSID) and there may be an opportunity to bring in the BQ as part of this. The INN Programme is in fact ready to implement a BQ. Dr Balocco expressed hope that a decision would be taken soon as the INN by itself is not sufficient for PV.

Read the full Executive Summary of the 77th INN Consultation here.

ASBM Releases Fact Sheet on Emerging Challenges to Interchangeable Biosimilars Policy

February 5, 2024

On January 31st, ASBM released a fact sheet describing a variety of proposed policy changes at the state and federal level which would weaken the interchangeable biosimilar standard, or circumvent the patient protections it provides. These include new bills and regulations at the federal level, as well as state legislation and proposals which threaten to undermine the hard-won gains of the patient and physician communities to ensure that only interchangeable biosimilars are substituted without physician approval.

Interchangeable Biosimilars: Emerging Policy Challenges

The fact sheet is the third in a series discussing interchangeable biosimilars and related policies. View the others below:

Physician Perspectives on Interchangeable Biosimilars

Interchangeable Biosimilars: Comparing Europe and the U.S.