Sunday, October 21, 2018

TECH SPECIAL.... Biosimilars - a lucrative business opportunity, but with many challenges


Biosimilars - a lucrative business opportunity, but with many challenges

Biological drugs are becoming an important component of modern healthcare, and more and more of new drug approvals fall into this category. Biosimilars – their generic versions – are widely viewed as a promising growth opportunity, especially by companies focussed on generic markets. Patents no longer cover the first wave of biologicals introduced about a decade ago, and these markets are up for grabs. A handful of pharmaceutical producers in India and several abroad are gearing up to cater to this opportunity, but the path to market is not as easy as for small molecules, given the significant intellectual property, clinical and regulatory challenges.
What is a biosimilar?
Simply put, a biosimilar is a biological medicine that is similar to another that has already been approved for use. While they are not exact copies of the drug from the innovator that they aim to mimic, they do have a very similar therapeutic value. This equivalence needs to be proven by a fairly arduous evaluation of quality, bioactivity, efficacy and safety – to convince regulators who grant the approvals that any differences are not clinically significant.
The market opportunity
The markets for biosimilars is reckoned to have reached $4.4-bn in sales in 2017, and is forecast to reach $25-bn by 2025, representing an impressive CAGR growth of 34%. This is still small when compared to the overall size of the global pharmaceutical industry ($1.1 trillion in 2015). The other point to be noted is that biosimilars still have a small share (2-3%) of the overall market for biological drugs, but this will rise as new drugs enter the market and regulators, prescribers, payers and patients all become more comfortable with these alternatives.
About 12 major biologicals with combined global sales of more than $67-bn currently are expected see generic competition once their patents expire by 2020. Many more will go off-patent post this period, presenting additional business opportunities.
Several companies are eyeing this market – including about a dozen companies in India. In the business for small molecule generics – the bread and butter business for all Indian generic players – competition has eroded prices and margins very significantly in recent times. This is most evident in the US market – the most important – where besides consolidation amongst buyers, regulatory scrutiny of manufacturing assets in India have also increased. This has squeezed margins for nearly all generic producers, and forced them to relook business strategies. One business some are eyeing in ther quest for better returns is biosimilars.
The growth drivers
The desire to curb healthcare costs is an important factor driving adoption of biosimilars – an aspect that assumes great significance given the high costs of most of these drugs. This is all the more so for developing countries as India, where few – even amongst the upper middle class – can afford to pay out of their pockets for drugs that cost tens of thousands of rupees for a single dose! In developed countries, with far more sophisticated markets and wide patient coverage through insurance, many payers are eagerly awaiting biosimilars for their cost effectiveness.
The competitive landscape
Most experts agree that the biosimilars business is unlikely to see the level of intense competition seen in small molecule generics, for several reasons. For one, the manufacturing of biologicals is a lot more demanding in terms of capital required; the complexity of the manufacturing process (mostly involving fermentation), and the intricacies of downstream processing & purification. The skill sets required in the business of biosimilars is very different from that widely available in the pharmaceuticals industry in India, and can be a limitation to rapid scale-up of competencies.
The players in the global biosimilars space can be broadly lumped in three broad categories: innovator companies who are keen to manage the drug through all stages of its lifecycle, including after expiry of its patent; small molecule generic players eyeing more lucrative business opportunities; and pure-play biosimilar companies.
There are only a few companies in the first category, but they do have the advantage of intimate knowledge of the product and its market. But they are handicapped by high cost structures and conflict of interest between the generic and innovator parts of their portfolios. In the second category are several Indian generic companies, whose biosimilar forays are still restricted to less semi-regulated markets (including India). While most do not have much experience with biologicals, they do understand manufacturing, have strong marketing presence, including in important overseas markets, and understand price-focussed selling that the generic business demands. The pure-play biosimilar producers include some ‘virtual’ companies, often staffed with experts from the biologics industry. These companies are likely to outsource manufacturing to contract manufacturers and even out-license products to companies with the ability to take it through to commercialisation.
Companies eyeing this opportunity must carefully evaluate several factors. The first is the competitive landscape amongst generic players themselves. There are several first- and second-generation products where a number of players jostle for market position, and margins can come under under pressure here too. The second factor to keep in mind is that innovator companies do still have some tricks up their sleeves, including the ability to slash prices to ward off competition. Another aspect to consider is the possible emergence of newer, more effective therapies that could edge out older generic versions from the market.
The regulatory challenges
Then there are the regulatory hurdles to overcome. Thanks to intense pressure from innovator companies, regulators in the all-important US market have been slower than their counterparts in Europe, for instance, to permit biosimilars. Their reluctance has been largely on the basis that unlike small molecules, for biosimilars the process, in a sense, makes the product. In other words, even minor deviations from the (often secretive) process of the innovator, as practiced by the generic supplier, could alter product characteristics and therapeutic relevance. But these concerns are exaggerated and regulators have slowly come to accept that biosimilars have merit and there is little reason to exclude them from the market.
As a result, in 2017, the US Food and Drug Administration granted a record number of approvals for biosimilars and the number of applications under consideration by the European Medicines Agency also continues to rise.
The development risks of biosimilars are also markedly higher than for small molecules. Their manufacture, almost without exception, involves living systems and cell lines, and a significant portion of manufacturing costs comes from downstream purification. The possibilities of success are in the range of 50-75%, compared to upwards of 90% in the case of small molecules.
A rewarding and growing business
But for those companies that do manage to overcome the challenges, the market can be rewarding. Price erosion for biosimilars is never likely to be as precipitous as for small molecules.
Biosimilars will also fulfil an important need for lower-cost advanced therapies and have been welcomed by countries such as India. The domestic market here will in itself offer significant opportunities for local companies operating in this space, but like in small molecules most leading players are looking to hone their skills here, test the local waters and then venture overseas. Partnerships will be one way in which they could reduce risks, make-up for lack of some competencies, and quicken the time to entry to market.

Chemical Weekly Issue date: 9th October 2018

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