HERCEPTIN has greatly improved survival rates in breast cancer. Unlike traditional drugs like aspirin that are made using chemical processes, this lifesaver is made using biological processes directed by genetically modified cells.
Such technologically intensive drugs are called biologics and are very pricey. Herceptin, made by Genentech in Tuas, costs $3,000 to $5,000 a month.
But even when it goes off-patent, its generic replacements may not be much cheaper because of the genetic technology needed to make them. This involves engineering the DNA of host cells (bacteria or yeast or human cells) to produce proteins of specified shapes and structures that bind to unique cell targets. For example, Herceptin binds to the Her-2 “growth switch” on breast cancer cells.
In effect, such host cells make these unique proteins by following a recipe provided by their modified DNA. However, two host cells of the same type having the same recipe will make proteins that may differ slightly from one another due to prevailing environmental factors.
Why? Even if you had a celebrity chef’s recipe for his signature dish, you will never quite replicate his masterpiece. Tiny variations in time and temperature he adopts, his self-cultivated herbs or self-made yogurt and so on determine the final taste. Just as your dish will never be exactly like his, generics of Herceptin, say, will not be exactly the same.
Such follow-on versions of original biologics are not called generics but “biosimilars”, a term heard a lot at the BioPharma Asia convention held this week here as biosimilars look like a good business category for local lifescience firms to leverage on as a business opportunity.
Whereas traditional drugs like aspirin are small molecules made using well-characterised chemical processes, biologics are huge molecules (of proteins) made using less predictable biological processes that go on inside living cells.
The two classes of molecules differ greatly in size and complexity. A convention speaker, Dr Wassim Nashabeh of Genentech, likened aspirin and Herceptin to a bicycle and a private jet in size and complexity. More than just strings of atoms, protein molecules are folded in complex 3-D ways. This folding is what makes a raw egg different from a cooked one. While the two forms are chemically identical, heat changes the molecular folding, thus changing the egg’s properties.
Traditional generics of aspirin, say, are copycat versions of the actual original molecule as it can be precisely replicated using standardised chemical processes.
By contrast, because biologics are made by specially engineered living cells, their molecular shapes and structures can vary within certain limits from batch to batch even when they are made in the very same facility. Thus a biosimilar that can do the same thing as the original biologic does not have exactly the same molecular structure. Each step in a biologic’s manufacturing process contributes to its complexity and functionality.
Countries have now passed laws that lay down rules on how to determine if a biosimilar is functionally equivalent to its original biologic. In the European Union (EU), a biosimilar law came into effect in 2006. Singapore put in place rules modelled after the EU in 2009.
The United States law came into effect in 2010 while its specific regulations were only issued last week.
The EU has approved 14 biosimilars while the US has approved none yet. Singapore basically allows those approved by the EU and US to be used here.
These laws enable a biosimilar to get regulatory approval in a much shorter timeframe than the original biologic. As several original biologics are coming off-patent by 2016, biosimilars present a great business opportunity.
In fact, given that a biosimilar is somewhat different from the original biologic in its molecular composition and the biological process by which it is made, some legal experts feel it may not even infringe the original’s patents. Yet drug regulators would consider it similar enough in safety and efficacy to be approved faster.
Experts say that while an original biologic may cost US$150 million (S$190 million) to US$250 million to bring to market, a biosimilar may cost only US$25 million to US$75 million. One reason is that an abbreviated approval pathway means that large clinical trials are bypassed.
Still, their greater complexity means that biosimilars present much higher costs of entry than traditional generics. As such, economists project relatively fewer biosimilar entrants than traditional generics that sprout when a traditional best-selling chemical drug like Lipitor goes off-patent.
This means that biosimilars will not be price- discounted as steeply as traditional generics. If so, biosimilar competition with biologic originals will look less like generic versus branded, and more like branded versus branded. This means that consumers might end up paying more for biosimilars than they would if biosimilars were just chemical generics.
This is so in the current market for the off-patent growth hormone (a biologic but one less complex than Herceptin), where biosimilars are competing against the original based not on price but ease of use such as needle-less pen dispensers.
Such competitive scenarios imply that biosimilars could mean much bang for buck for a small player like Singapore.
Credits: Andy Ho, The Straits Times, Singapore, 24 March 2012