Note: The story will largely focus on the U.S market because of the potential opportunity it provides and the increasing focus of Biosimilar companies to gain a foothold in the market
Innovators and Copycats
In 1989, Pfizer chemists (pharmaceutical giant) in East England were trying to synthesize a simple molecule drug that they thought might treat high blood pressure and chest pain. The low priority project had pretty disappointing results initially and showed little to no promise. In 1993, during a clinical trial, researchers were trying to study the effects of the drug on a group of Welsh Mineworkers. After a disappointing review, the researcher finally asked if the participants noted anything else they might want to report. One of the men put up his hand and said, "Well, I seemed to have more erections during the night than normal," and everybody else kind of nodded and said, "So did we." On that gloomy evening in South East England, the world had finally chanced upon Viagra, the miracle drug. It took another 4 years for the FDA (Food and Drug Administration, USA) to approve the magic pill, but at the end of it all Pfizer had in its hands what is often touted as a "blockbuster drug."
The point here is that success in this market is deeply intertwined with the research and development process that characterizes the pharmaceutical industry. It might take 5 years for you to develop a new drug and you might still need another 10 years to clinically test the product and gain approval from the regulatory agencies. This is an extremely capital intensive process and the only way to remunerate the investment of the pharma company is to protect the investment through patent protection. Viagra's product patent lasts a whole 20 years (US) and no other company can sell the same compound during that time. This way the companies can be incentivised to invest more in research thereby ensuring a steady supply of new innovator drugs.
Once the patent expires, however, copycats can market their own version of the drug. These copycat drugs are called generics and companies can replicate the manufacturing process with relative ease. In order for a company to market a generic, the FDA must agree that the generic is interchangeable with the innovator product and that it contains the same active ingredient. Because of the relative simplicity involved in manufacturing generics, the industry also breeds intense competition. This increasing competition has interestingly spun off a new proxy war of its own with its own cast of complex characters.
The Need for Complexity
Ever since modern medicine started to emerge post the Industrial Revolution, simple molecules have been used to treat most diseases. While these formulations were highly effective against some illnesses, it was proving particularly ineffective against more complex diseases like cancer. Our immune system has evolved over millions of years to specifically defend against intruders by finding and destroying anything that's not supposed to be inside our bodies. But cancer isn't like most diseases. It's not caused by an invasion of a foreign pathogen. Instead, it's a byproduct of rogue cells within our body that don't necessarily act the way they should. To this end, using simple molecules to defend against a barrage of mutating versions of our own cells is an exercise in futility. In the process of killing the bad cells, these drugs will simultaneously annihilate the healthy cells too. So the cut-slash-kill method isn't particularly effective. What we instead need is a 'biologic' or a complex protein isolated from natural sources that can mimic our immune cells.
Although initial attempts to replicate and genetically modify antibodies failed quite miserably, the field of biologics has begun to show considerable promise since the turn of the century. Also, the advent of biologics isn't a particularly new phenomenon. We have had vaccines for a good half century now and considering most vaccines are complex living agents that resemble a disease-causing microorganism, they fit under the ambit of biologics pretty well. However, it's only in the last 25 years that new developments in genetic engineering/recombination techniques and targeted therapies have begun to open up new opportunities and this, in turn, has breathed new life into the field of biologics and with it, its copycats — biosimilars.
Similar but not same
Unlike small molecule drugs like Viagra that can be chemically synthesised using a straightforward approach, biologics are harvested from living cells and are often produced using complicated manufacturing processes. Most modern biologics are assembled inside vats — or bioreactors — that house genetically engineered microbes or cell cultures and can often take a whole decade of research to perfect. So replicating the process isn't exactly a cakewalk and often times the copycat version (biosimilar) can differ from the innovator biologic.
Michael Yang, President of Immunology at Janssen Biotech described it this way — "biologics are living proteins, and living proteins can't be copied, in the same way, that one oak tree is different from another, even though they are both classified as oak trees." A biosimilar is not equivalent to the original biologic, instead is highly similar in the way that it interacts with the human body. The design and creation of a biologic drug is complicated enough that a biosimilar isn't going to be precisely the same as a biologic. So the FDA has to be extremely meticulous whilst approving the drug and ensure that it acts the same way as the reference(innovator) biologic would. So in addition to the lengthier, more expensive development process, biosimilars also entail a more time-consuming approval process characterised by several phases of clinical trials. While multiple Indian companies have forayed into manufacturing and marketing generics in developed markets, only one Indian player seems to be trying to make a dent in the biosimilar space.
