IQVIA Report suggests US regulatory reform to fill “biosimilar void”

US President Donald Trump

New Delhi, 24 March (Chetali Rao and K M Gopakumar) – The recent report from IQVIA Institute for Human Data Sciences titled “Assessing the Biosimilar Void in the US”, proposes regulatory reform as the solution to fill the biosimilar void.

Though the report focuses on the United States, regulations on the marketing of biosimilars in developing countries also present similar obstacles to market competition and affordable biosimilars.

[Biosimilar is the non-originator version of a biotherapeutics.  Biosimilar void refers to the lack of availability of biosimilars even after the expiry of patents on the originator reference product.]

The reports states: “Biosimilar clinical trials often require study populations larger than the reference product, and retrospective analyses suggest the efficacy endpoints in comparative efficacy studies add limited scientific value to successful biosimilar development programs”.

The report proposes that the current regulatory requirements for the marketing approval of biosimilars in the US need to be simplified in the light of current experiences and information, which have shown that biosimilars are safe and efficacious.

It recommends that “regulatory requirements for biosimilars should be re-evaluated, potentially simplifying development programs”.

The current regulatory pathway for the approval of biosimilars in most jurisdictions including the United States requires comparative clinical trials, which consume time and financial resources. The Biologics Price Competition and Innovation Act, which provides the regulatory framework, mandate biosimilar developers to establish that “there are no clinically meaningful differences between the biological product and the reference product in terms of safety, purity and potency.”

Similarly, to achieve interchangeability, the biosimilar developer has to demonstrate ethe absence of any additional risk to patients.

According to the report, “This can result in large, costly clinical trials that may take an extensive amount of time to complete”. It states the development costs for biosimilars are estimated to be between USD100 million to USD250 million, and biosimilar developers andt manufacturers must be able to recoup these development costs as well as the costs of manufacturing and marketing these medicines once available to patients.

Further, the report states that biosimilar development can take six years and this long duration brings a great degree of unpredictability regarding the decision on biosimilar development. During this long development period a product with better safety and efficacy than the reference product may come into the market, and this would diminish the commercial potential of the biosimilar. Similarly, originator companies may launch a new formulation of the reference products and actively shift patients from the reference product.

The “Biosimilar Void”

The IQVIA report highlights that as of the end of 2024, only 14 out of 62 biologics without patent protection have biosimilars in the US. Over the next decade (2025–2034), 118 biologics are expected to lose patent protection and 90% do not have any biosimilar in development.  Alarmingly, at present only 12 biologics losing patent protection between 2025 to 2034, have biosimilars in development. These 118 biologics represent a significant market opportunity for biosimilars of USD 234 billion sales in invoice prices in the US, which can mean savings to the healthcare system.

The 118 biologics facing patent expiry have a median forecasted peak annual sale of USD312 million. Of these, 48 biologics are forecasted to have high sales i.e. sales of more than USD500 million annually before patent expiry, while 70 biologics have low sales of less than USD500 million annually before patent expiry.

While it may seem that biosimilar developers typically target high sale biologics, this is not always an indicator as only 23% (11) of high-sales biologics currently have biosimilars in development. This contrasts sharply to low-sales biologics where only a single molecule (1%), has biosimilars in development.

According to the report, in terms of therapy areas, biosimilars in the pipeline do not reflect diversity. The upcoming patent expiries span 13 therapy areas, while the biosimilar pipeline is heavily concentrated mainly in two therapy areas – oncology and immunology (19%), which account for 92% of molecules with biosimilar development. This is also reflected in the current biosimilar market where nine of 14 molecules with marketed biosimilars are in oncology or immunology. For therapy areas outside of immunology and oncology, like diabetes, haematology and neurology, there is a huge void.

The report also highlights that developing biosimilars for rare diseases presents a significant challenge. Of the 118 patent expiries, 53 are for rare diseases for which 98% have no biosimilar in the pipeline. Another 43 – which have non-orphan indications – 88% have no biosimilar in development.  However, only one biologic with only orphan indications, eculizumab, has biosimilars in development, and 88% of all patent-expiring biologics with at least one orphan indication do not have biosimilars in the pipeline. Of the 53 orphan-only biologics, 10 (19%) are high sales which may typically attract biosimilar developers. However, difficulties with clinical development of orphan biologics further deter biosimilar competitors.

[A “non-orphan indication” refers to a disease or condition for which a drug is being developed or marketed, but which does not meet the criteria for being designated as an “orphan drug” by regulatory agencies.

[On the definition of “orphan drug”, the US Food and Drug Administration (FDA)  Explainer states: “An orphan drug is defined in the 1984 amendments of the U.S Orphan Drug Act as a drug intended to treat a condition affecting fewer than 200,000 persons in the United States, or which will not be profitable within 7 years following approval by the FDA. An Orphan designation qualifies the sponsor of the product for:

– Seven-year marketing exclusivity to the first sponsor obtaining FDA approval of a designated drug;

– Tax credit equal to 50% of clinical investigation expenses;

– Exemption/Waiver of PDUFA application (filing) fees;

– Assistance in the drug development process;

– Orphan Products Grant funding”.]

Another challenge according to the IQVIA report is the increased barriers faced by complex biologics, such as antibody-drug conjugates, bispecific antibodies, cell therapies, and gene therapies. From 2025 to 2034, patent protection for 16 complex biologics will end, yet none currently have biosimilars in development. Half of the complex biologics set to lose patent protection are cell or gene therapies, which are exorbitantly priced with prices running as high as USD4.4 billion. Therefore, spending has been lower on these drugs representing significant access problems.

As these complex biologics represent a significant share of biologic medicines, they continue to constitute an increasing share of biologic medicines. The absence of measures to overcome or offset the inherent challenges of bringing complex biosimilars to market will further limit the sustainability of the biosimilar market.

However, the report overlooks the fact that patent thickets are one of the contributing factors in the delay to launch biosimilars in many jurisdictions. It is a well-known tactic among biologic manufacturers to file numerous patents for a single drug, a practice that can significantly stifle competition and innovation.

One of the most striking examples of this is Adalimumab (Humira), a blockbuster anti-inflammatory biologic used to treat rheumatoid arthritis, Crohn’s disease, psoriasis, and other conditions. Humira’s originator, AbbVie, had strategically filed multiple patents to extend its market exclusivity, employing what is known as a “patent thicket.” This tactic has allowed Humira to reign as the world’s best-selling drug, generating over USD14.4 billion globally in 2023.

This strategy of layering patents creates significant barriers for biosimilar manufacturers as it leads to costly and lengthy patent litigation which consequently has a chilling effect on biosimilar competition. The impact of such practices on healthcare costs and patient access to biological drugs cannot be overstated. By erecting these patent thickets, companies not only maximize their profits but also prolong the period during which patients are forced to pay exorbitant prices for these drugs, or to not have any access at all. The consequence is a healthcare system that prioritizes corporate profits over patient welfare.

Reducing redundancy in regulatory pathways and addressing the issue of patent thickets could significantly lower the development cost of biosimilars, encouraging more biosimilars to enter the market and address the identified “ biosimilar void”. – Thirs World Nwrwork