Join a clinical trial? The success rate of such trials is higher than you thought, but still awfully low overall; especially for Alzheimer’s.

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The News:

Instead of less than 10% of drugs reaching the market, a new study has found that almost 15% of new compounds pass clinical trial–which still suggests that it’s pretty daunting. Clinical trials give us a chance to test how a new drug or therapy interacts with the body and whether it is any good at curing disease before being launched.

Previous studies estimated that the likelihood of a drug at Phase 1 making it all the way to the market was between 3% and 9%, says However, a new study carried out by researchers at Massachusetts Institute of Technology (MIT), and published in Biostatistics, has found that the outlook may not be quite so bleak, with a success rate of closer to 14%.

The study followed more than 21,000 compounds through the clinic between 2000 and 2015. The group at MIT defined key characteristics, including whether a compound was undergoing Phase 1, 2, or 3 clinical trials so that a diverse range of studies could be analyzed.

Once the fate of each of the compounds had been discovered, the group calculated the probability-of-success (POS) for all drugs and indications, which researchers and investors then utilize to decide whether to move a drug forward.

The study coordinators defined the drug-advancement pathway as the development of a drug for a specific indication. Overall, 13.8% of all drug development programs were eventually approved, which is higher than the 10.4% reported in a previous, smaller study. The study also found that there was an increased POS at each of the clinical trial phases, particularly at from Phase 2 to 3, which increased from 32.4% observed in a previous study to 58.3%.

But the numbers vary greatly among indications. In the case of infectious diseases, 1 in 3 drugs was approved, while around 3% of cancer drugs succeeded. This is despite suggestions that too many cancer drugs are making it through the clinic.

A study carried out by King’s College London and the London School of Economics found that the majority of EMA-approved cancer drugs had not improved survival or quality of life during clinical trials. In addition, of those that did improve survival, the benefits were limited, with patients surviving for just an extra 5.8 months maximum.

The POS for the different therapeutic areas between 2005 and 2015 showed that ophthalmology had the highest rate of success, while oncology had the lowest. Although the mortality rate from cancer has declined, it remains one of the biggest causes of death in the world. This has drawn in research groups, biotechs, and pharma companies–all eager for clinical and financial success.

Steve’s Take:

The above paper helped clarify for me the current status of clinical trial test results, and boy was it an eye-opener.

In our circle of friends and acquaintances, two recently participated in trials of different cancer-therapy candidates: 1) the checkpoint inhibitor Keytruda, and 2) the CAR T-cell therapy Kymriah.

Paul had been a professional tennis coach for many years and after retiring, learned that he had metastatic melanoma which had spread to his lungs and other organs. He was put on Merck & Co.’s Keytruda, and to make a long story short, experienced what is called a complete response, meaning the cancer had completely disappeared.

Briefly, PD-1 is a so-called checkpoint protein on immune cells called T cells. It normally acts as a type of “off switch” that helps keep the T cells from attacking other cells in the body. It does this when it attaches to PD-L1, a protein on some normal (and cancer) cells. When PD-1 binds to PD-L1, it basically tells the T cell to leave the other cell alone.

PD-1 inhibitors that target PD-1 include Keytruda and Bristol-Myers Squibb Co.’s Opdivo.

One concern with these drugs is that they can allow the immune system to attack some normal organs in the body, which can lead to serious side effects in some people, including death.

Next is our neighbor Bill, who was diagnosed with lymphoma, a cancer that begins in infection-fighting cells of the immune system, called lymphocytes. These cells are in the lymph nodes, spleen, thymus, bone marrow, and other parts of the body. There are two main types of lymphoma, and Bill had Non-Hodgkin, the most common. Bill also experienced a complete response when put on a CAR T-cell therapy called Kymriah, from Novartis AG.

Until recently, the use of CAR T-cell therapy has been restricted to small clinical trials, largely in patients with advanced blood cancers. But like checkpoint inhibitors, these treatments have nevertheless captured the attention of researchers and the public alike because of their remarkable results when all other treatments had stopped working.

In Paul’s case, the cancer came back again in what’s called a relapse or recurrence. Bill is still in the clear.

All of which leads me to this new examination of recent clinical success rates.

The aforementioned paper published by Chi Wong, Andrew Lo, and Kien Siah of MIT and their co-workers represents an eye-opening discourse on clinical trial probability-of-success (POS) data. It appears to be the largest such effort yet.

Addressing the data in the MIT group’s analysis, Derek Lowe from Science Translational Magazine, writing for his own personal blog, has constructed a fascinating piece which estimates the POS and other related risk characteristics of 185,994 unique trials of 21,143 compounds from Informa Pharma Intelligence’s Trialtrove and Pharmaprojects databases from January 1, 2000 to October 31, 2015.

Lowe claims that his is the largest investigation thus far into clinical-trial success rates and related parameters. To process this large amount of data, Lowe & Co. developed an automated algorithm that traces the path of drug development, infers the phase transitions, and computes the POS statistics in just hours.

Bottom Line:

Lowe & Co. came up with higher success rates than the other studies in this area. The standard estimates for overall probability of clinical success is about 10%, but this study has 13.8% of all pathways actually making it through. The biggest difference is in the Phase 2-Phase 3 transition, and this is thought to be due to better coverage of missing trials.

A closer look at the data, though, tells an even more revealing story, namely, that the overall POS figure is profoundly reduced by low success rates in oncology. Of the 41,040 total pathways in the set, 17,368 are for oncology. The POS of everything outside of oncology is 20.9%, while the POS in oncology itself is 3.4%.

If looking 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, curiously. Oncology is still the lowest of entire group.

What about orphan diseases? Using the NIH and EU definitions, success rates are lower in every way in these areas. Over half the trials so classified are in oncology, and their POS is a flabbergasting 1.2%. If one eliminates all the oncology pathways, the POS for “orphan everything else” is 13.6%.

People can differ about what the “right” figure should be, but Lowe says,

“there seems no doubt that half or more of the drug-discovery and development work in the US and EU is going towards cancer indications.”

My final thought is that Alzheimer’s disease research and resulting trials have been an absolute, abject failure. Bottom line? There are no effective treatments. And even though Alzheimer’s is now a national medical emergency, with the arrival of us boomers into the general population in increasing numbers, only one-tenth of research funding is spent on all Alzheimer’s as is spent on cancer. This just doesn’t make sense.

Steve's Take: With #clinicaltrial failures piling up, more #research funding for #Alzheimers is needed or it will surely bankrupt #Medicare in the very near future Click To Tweet

While clinical trials of potential Alzheimer’s prevention and treatment therapies are ongoing, our government needs to drastically increase the funding for them, or the cost of caring for Alzeheimer’s patients will surely bankrupt Medicare in the very near future.

Is that what we the people want?

This emergency is upon us presently, and it desperately requires us citizens to prevail upon our elected representatives to adopt the necessary research funding measures now.

After all, isn’t that their job?

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