https://blogs.sciencemag.org/pipeline/archives/2017/05/12/tu...>And that reshaping is a pretty lively process. Witness the news that Roche has had a major unexpected clinical failure with their antibody therapy Tencentriq (atezolizumab) in bladder cancer. This is another antibody targeting the PD-1/PD-L1 system, like Keytrude, Opdivo, etc. (in this case, it’s going after PD-L1 itself), and it was the first one approved against any form of bladder cancer. It’s also been approved for metastatic non-small cell lung cancer, which is a more traditional indication in this area, if by “tradition” we mean the last couple of years. The bladder cancer approval, though, was an accelerated one after just Phase II data, with re-evaluation to come after the Phase III numbers came in.
>Well, now they’re in, and the drug missed its primary endpoint. This not only puts Tencentriq’s continued approval for this indication in doubt, but it cannot be good news for the other companies in this space who are targeting it as well. Opdivo (nivolumab) from Bristol-Myers Squibb got approval in February, Pfizer and Merck KGaA’s Bavencio (avelumab) got a similar accelerated approval just a couple of days ago. Merck’s Keytruda (pembrolizumab), meanwhile, showed a good response Phase III (so much so that the trial was cut short), and is under review at the FDA, and there’s AstraZeneca’s entry in this area Imfinzi (durvalumab), too.
https://blogs.sciencemag.org/pipeline/archives/2015/11/17/ap...
>But a similarly targeted drug from Clovis Biotechnology, rociletinib (which is one of the recent acrylamide-containing irreversibly covalent kinase inhibitors), ran into some big trouble. The FDA wants more data, for one thing, and the reason that they want more data is that Clovis submitted preliminary clinical data to them earlier that have not held up. That was clearly done because they were in a race with AstraZeneca (and with time in general), but you’re walking on – or sprinting across – a flaming tightrope when you try something like that, and the results are clear. Clovis’ stock fell about 75% on the news
https://blogs.sciencemag.org/pipeline/archives/2018/02/02/a-...
>A closer look at the data, though, tells an even more different story. That overall POS figure is heavily dragged down by low success rates in oncology. Of the 41040 total pathways in the set, 17368 are for oncology (note that the same drug tried against two different types of cancer will show as two different pathways). The POS of everything outside of oncology is 20.9%, which the POS in oncology itself is 3.4%. If you look at lead indications, instead of all indications, the POS goes up overall (which is in line with earlier studies). But the Phase 2 to Phase 3 transition rate actually goes down a bit, interestingly. Oncology is still the lowest of bunch.
https://blogs.sciencemag.org/pipeline/archives/2017/01/23/i-...
>The timing of this report from the FDA is surely no accident, but it’s always a good time to think about this: the great majority of all drugs that enter clinical trials fail. They fail because they don’t do anyone any good, or because what good they might do is outweighed by some serious and unexpected harm. Around 90% of all compounds that start in the clinic never make it out. Even by the time you get to Phase III – and these are drugs that have apparently already worked in sick patients by that point – the failure rate is still nearly 40%. Drug projects fail constantly.
>It’s hard, sometimes, for people who’ve worked in other industries to appreciate this. Drug development is a unique combination of very high regulatory burden and very high failure rates, so it’s temping to say that the regulations cause the failures. But that isn’t true. Biology causes the high failure rates – specifically, our lack of understanding of biology.
Calling a field where, after spending tens of millions of dollars of development on a product, only 3.4% of them even work at all a branch of "engineering" is perhaps a novel perspective. If 19 out of 20 bridges promptly collapsed after being constructed, the word "engineering" might have different connotations.
As usual in biotech, when I see someone posting simple, obvious untruths for personal gain, I wonder: delusion, or mendacity? Fast DNA synthesis will not solve the actual bottleneck, which is, and has been for a century, clinical trials in humans.