China's First Homegrown Pharma

by: Derek Lowe

The Wall Street Journal had an article on a new HDAC inhibitor from Shenzhen Chipscreen (full text here from The Australian). It's worth highlighting. Epidaza (chidamide) appears to be the first homegrown drug discovery and development effort to reach regulatory approval in China.

Their founder, Xian-Ping Lu, was working at Galderma before he went back to China in the early 2000s to start his own company. Chidamide is a start-to-finish compound for Chipscreen, and that puts China on a rather short list of countries that have demonstrated the ability to do that in small molecule drug development. You see claims for this sort of thing that don't quite hold up, but this certainly appears to be the real thing, and congratulations to them.

Some thoughts: first off, this would be the fourth (I think) histone deacetylase inhibitor to get regulatory approval somewhere. That class of compounds was a hot topic for development ten or twelve years ago (I was working on some then, not to any great effect). It's the first class of pharmacological agents deliberately targeting epigenetic signaling, and the complexities of that field have made things run slower than people were hoping. As this article in Nature Reviews Drug Discovery put it:

Oncology drug developers have long been interested in the role of HDACs, which can repress gene transcription by modulating chromatin structure, because altered expression of HDAC enzymes is often seen in tumours. HDAC inhibitors, the researchers hoped, could drive the re-expression of silenced genes, including those that encode tumour-suppressing proteins. However, the failure of multiple HDAC inhibitors to show activity in most cancer types, especially in solid tumours, has over the years led to an outbreak of 'HDAC inhibitor fatigue' in the research community β€” distinct from the physical fatigue many patients experience as a common side-effect of the drugs. β€œThe wave of excitement surrounding this early class of epigenetic drugs has waned and been replaced by a wave of scepticism,” says Jean-Pierre Issa of Temple University in Philadelphia, Pennsylvania, USA, who researches epigenetic mechanisms in cancer.

As these mechanisms get more worked out, the hope is that the HDAC compounds can get on a more sound footing, but for now, they're minor players in the oncology world. (I have no feel for how well chidamide compares to the other marketed compounds).

The second thought is whether Chipscreen plans to seek approval to market the drug anywhere outside China. I hope so - it would be good for Chipscreen and good for the global reputation of the Chinese drug industry. What would be good is if China becomes another market like the US, EU and Japan, where companies from each region get drugs approved in the others. There are (or can be) some slightly different requirements in each, and sometimes regulatory authorities will let something through in one that doesn't fly in the others, but the serious drugs end up in all of them and other markets (Canada, South America, Australia, Israel and so on) besides. (I'm excluding some of the no-efficacy-just-safety compounds from Japan from that category). What China does not need is to become a sort of regulatory backwater. The sheer size of the market there argues against that happening, but if the drug industry there continues to develop, the government could conceivably start tipping the scales towards China-discovered compounds. Getting chidamide out into the rest of the world would help to get things off to a good start.

The last thought comes from the statement in the article that the drug cost about $70 million to develop. That is indeed cheap, as little as ten per cent of what it would cost to do that in the US or the EU. And why is that? One's first thought is cost of labor, but although it can be cheaper to outsource some parts of drug research to China, it does not save you 90% by any means. Most of the money spent in a drug project is spent in the clinic, so my guess is that Chipscreen was able to get their clinical trials done for much less money than it would cost over here. Just how and where those savings came in, though, I couldn't tell you. If that's a real effect, though, and if those are real figures, then the Chinese companies would appear to have a huge cost advantage on the rest of their worldwide competition, which makes you wonder why it's taken until 2015 for the first locally-produced small molecule to show up. I should note as well that the other big multinational drug companies have not swarmed into the Chinese clinical trial space, not to the degree you'd expect if there were really 90% savings to be realized by doing so. This part will remain an open question for now.

But all of that aside, I'm glad to see Chipscreen make it through with their own compound. I'm glad to see any small company do that, Chinese or not, but their position as the first to do it in China is something that no one can take away from them. People have been waiting for it to happen, and here it is.

Disclosure: None