Indian Company Moves To Provide Affordable Insulin Biosimilar In Europe As Patents Rise

Bangalore-based Biocon may become the first Indian company to offer a biosimilar insulin in Europe. And the patent and pricing story is interesting.

Biocon plans to apply for approval for its biosimilar in the EU, US, Australia and Canada at the end of this year and beginning of next year.

Biosimilars are copies of biological compounds, complex molecules that originate from natural sources. However, they are not thought of as generics because of their complexity. Unlike generic compounds, biosimilars can be much larger – thousands of atoms in size. And biosimilars, such as insulin, are never identical replicas of an originator biologic. That’s only possible with knowledge of the exact manufacturing process.

The applications follow Biocon’s first move into a highly-regulated market earlier this year; it received marketing approval in Japan. It signals a move to increase the number of competitors in the insulin market. Just three manufacturers (Eli Lilly, Sanofi and Novo Nordisk) control almost 90 percent of the market, worth US$20.8 billion. Yet insulin is out of the reach of many millions of people who need it; the life expectancy of a child with Type 1 diabetes in parts of rural sub-Saharan Africa can be a matter of months due to lack of access.

Several other biosimilars are in production since the originator product patents expired in 2014 in both Europe and the US; Merck and Samsung Bioepis and Eli Lilly have produced biosimilar insulins.

So far, however, only Eli Lilly’s has been approved in Europe. Abasaglar was approved in October 2014, and was based on Lantus, a multibillion-dollar insulin produced by Sanofi. The US FDA has yet to approve any biosimilar insulins either, although Abasaglar was assessed and approved as if it was a new insulin at the end of last year (it did not go through the FDA’s specially-created biosimilar regulatory pathway which is why it’s termed a “follow-on” rather than a biosimilar).

Eventually, it is hoped that biosimilars will reduce the cost of insulin, which can be up to 45 times higher than other non-communicable disease medicines and unaffordable to those on low incomes. In a number of countries, insulins cost at least 3 days’ wages according to a charity, Health Action international (HAI).

And prices are increasing dramatically according to figures in the Journal of the American Medical Association.

Indeed, Biocon says there is a massive unmet need for affordable insulins both in emerging markets and richer countries. “As the largest Asian insulins player our aim over the next 10 years is to provide our insulin products to ‘one in five’ diabetes patients in need of insulin-based therapy anywhere in the world,” said Kiran Mazumdar Shaw, chairperson and MD at Biocon.

Curiously, lack of insulin is not down to patents.

There are no patents on human insulin, a kind of insulin whose method of manufacture was developed some 40 years ago. Yet price increases reported in the US affected all insulin types, including this older cheaper form.

Those patents that do exist tend to be on analogue insulins – genetically altered versions of human insulin that make it more rapidly or slower-acting. But many are on a patent cliff.

There is no shortage of insulin either. There are 39 insulin manufacturers worldwide – including Indian and Chinese suppliers – but less than 10 percent have taken out patents.

There’s a growing demand for insulin too. The first WHO global report on diabetes, released earlier this year, showed adults living with diabetes had almost quadrupled since 1980 to 422 million.

Yet 95 years after its discovery, lack of access to affordable insulin remains a key impediment to successful treatment and results in needless complications and premature deaths says WHO.

One reason is that diabetics are increasingly prescribed more expensive analogue insulins. That’s despite evidence that they provide any significant advantages over cheaper human insulins says WHO.

Thirdly, patents may not exist for insulin, but many exist for delivery mechanisms – like pen devices – and the prices of these devices is rising. The worry is that people could be stuck with one delivery device for one particular kind of insulin, say Jing Luo and Aaron S Kesselheim of Harvard Medical School. Speaking earlier this year, Hans Hogerzeil, professor in global health at the University of Groningen, said: “It is like a printer, the printer is cheap but the ink cartridge is the same price as a new printer.”

Finally, there may be many suppliers globally, but few suppliers in any one country. Some 23 companies only supply in one country, according to a three-year global study, called Addressing the Challenge and Constraints of Insulin Sources and Supply (ACCISS). In many countries, insulin is exclusively supplied by just one or two of the big three, according to David Beran, a researcher at Geneva University Hospitals and the University of Geneva and ACCISS author. Suppliers are concentrated and buyers are fragmented and scattered.

Governments are also responsible for some of the costs.  Extensive studies of insulin prices and tariffs, carried out by ACCISS, reveal that massive taxes, duties and other mark-ups within countries can ramp up the final cost of insulin. What’s more, there are hundreds of patents on insulins in development; including on oral inhaled insulin.

The big three have industry initiatives to provide insulin to some recipients in poorer countries, although researchers say data has been lacking so far that reveals how many people actually benefit.

So, that’s why everybody’s waiting for the effect of competition from biosimilars. “I think it’s a great thing because it will increase competition. But the question is how will that translate into either a decrease in prices or a change in the market?” said Beran.

Dramatic price-drops seen when generics enter a market are not expected because biosimilars are far more expensive to make and distribute. Experts expect more modest 15 percent reductions or more.

But it’s unclear yet what other biosimilars are being produced around the world – from the Middle East to China – and how they fare in terms of quality.

Researchers also wonder whether complex biosimilar regulations in richer countries are deterring the approval of biosimilars or ensuring quality. The EU has licenced biosimilars for over a decade, for instance, but the equivalent US regulatory pathway is so complex that no biosimilar insulins have been approved by it.

Part of the US regulatory system is even dubbed the patent dance, where biosimilar manufacturers and originators must confer over which patents might be infringed before approval in a series of predetermined steps; several companies are mired in patent disputes; and there’s also much debate over the extent to which originator and biosimilar molecules must be interchangeable.

ACCISS will publish further studies on biosimilar manufacturers, regulatory pathways and insulin industry initiatives towards the end of the year.

Many, including Hogerzeil, reckon it will be new global health policy interventions, not just new biosimilars, that will lead to meaningful cost reductions for patients with diabetes who require insulin. He reckons insulins should be incorporated into the WHO prequalification system (which he helped to establish).

 

Image Credits: WHO/Tania Habjouqa