[BioNOW] The Similar Yet Different World of 'Bokje Yak'... Generics and Biosimilars

Synthetic drugs are 'Generics' and bio drugs are 'Biosimilars'
Biosimilars are 'similar'... must undergo all clinical trials

Biosimilar developers also working on 'interchangeable biosimilars' and 'biobetters'

Celltrion's world-first developed monoclonal antibody biosimilar 'Remsima'

[Asia Economy Reporter Chunhee Lee] The medicines we take orally or receive via injection are broadly divided into two types. Based on their components and manufacturing methods, they are commonly categorized as synthetic drugs, often called 'chemical' drugs, and biopharmaceuticals.

However, there is one more special concept related to medicines: the 'generic drug' of each medicine. Newly developed 'innovative drugs' are protected by patents for a certain period, safeguarding the related rights. This is to protect the enormous funds and time invested by the developing companies in new drug development.

Typically, it takes about 10 years just for the clinical process to determine how effective and safe a drug is when administered to humans, requiring significant time and funding. The high prices of expensive drugs like Zolgensma (2.8 billion KRW in the U.S.) and Kymriah (360 million KRW domestically) reflect not only the high manufacturing costs after commercialization but also the recovery of these development costs.

Once the patent expires, not only the company that developed the innovative drug but also other pharmaceutical companies can develop generic versions of the drug. Since these generics are made by analyzing already disclosed drugs to create similar ones, development costs are drastically reduced, and the drug prices recognized by the market or government also decrease.

Generics are 'the same,' but biosimilars are 'similar'?

The generic drugs of synthetic medicines and the generic drugs of biopharmaceuticals are called by different names. Generics of synthetic drugs are called 'generic' drugs, while generics of biopharmaceuticals are called 'biosimilars.'

Generics are generally considered easier to produce. For synthetic drugs, if the chemical formula of the main ingredient is known, it is relatively easy to make a drug with the same ingredient. In fact, approval can be obtained by proving this through a 'bioequivalence' test that verifies whether the original drug and the generic have the same effect in the human body. This process is known as a 'bioequivalence study.'

However, the requirements for biosimilars are quite different. Biosimilars require 'similarity,' not 'equivalence.' Because biopharmaceuticals are produced based on living organisms, it is practically impossible to make them exactly identical to the original product.

Since completely identical cells are not used from the start, and manufacturing processes such as culture conditions and purification methods differ slightly, the resulting products inevitably have slight differences, making it impossible to demand perfect identity. On the other hand, because of this, biosimilars cannot rely on abbreviated procedures like non-clinical trials or bioequivalence studies as generics do; they must undergo formal clinical phases 1 to 3, just like the original drugs, to enter the market.

Not all biosimilars are the same... 'Interchangeable' or 'better'

When generics or biosimilars are introduced, the market share of the original innovative drugs is significantly impacted. For example, the epilepsy treatment drug 'Vimpat,' known as the world's number one, saw its prescription volume nearly halved within two months after its U.S. patent expired last March. Because competitors prepared generics in advance to coincide with the patent expiration, they quickly entered the market.

The world's best-selling drug, 'Humira' (active ingredient adalimumab), generated annual sales of $32.055 billion (about 42.4729 trillion KRW) last year alone, showing that successful new drug development brings enormous profits to companies. Despite biosimilars like Celltrion's 'Yuflyma' and Samsung Bioepis's 'Imraldi' entering the market, Humira has maintained its global sales leadership for over ten years.

Therefore, companies also pursue market share defense strategies through additional research and development (R&D) on existing innovative drugs. Regeneron, which developed 'Eylea' (active ingredient aflibercept), a treatment for macular degeneration and diabetic retinopathy that generated sales of about $9.4 billion (approximately 12.455 trillion KRW) last year, recently applied to the U.S. Food and Drug Administration (FDA) for approval to double the dosing interval of Eylea.

This strategy exploits the fact that biosimilars are not exactly identical to the original drugs. Unless a biosimilar is designated as 'interchangeable,' the original drug cannot incorporate results from additional R&D. Currently, only 'Semglee,' a biosimilar of the diabetes drug 'Lantus,' and 'Siltyzo,' a biosimilar of Humira, have been approved by the FDA as interchangeable biosimilars, highlighting the difficulty of development.

There are also 'biobetters,' which are improved versions of original drugs. These improve safety, efficacy, or utility compared to previously approved drugs, with representative examples including modifications in administration methods. For instance, products initially developed only for intravenous injection (IV) have been improved for subcutaneous injection (SC) to enhance dosing convenience, or the drug's duration has been extended so that instead of weekly or monthly injections, patients can receive doses every 2 to 4 weeks or even every six months.