Prevalence of the disease - if it only impacts 1/100 million, going to be hard to ever find sufficient patient population to test and recoup your investment.

Existing quality of treatments - if there are already efficacious drugs on the market - how sure are you that this new therapy will be best in class? Only being as good as the status quo is not an ideal competitive position. Conversely, if there is an unmet need because a disease is so lethal/debilitating, regulatory agencies can give latitude in approvals.

Likelihood patient compliance - if it is the most effective drug in the world, but requires intravenous infusion six times a day - nobody is going to adhere to that. GLP drugs are effective, but there is a needle-phobia that is preventing patients getting on board with the idea. Which is why there is an arms race for the first company to develop an oral version.

Toxicity - all chemicals are poisonous. Yet some have a lower therapeutic window than others. If you drug does what it should, but if you take 2x as much and it gives you a heart arrhythmia that is going to be a tough approval for anything but the most deadly conditions.

Good reasons:

* Most drug candidates just don't work

* Even among the drug candidates that do, figuring how to safely deliver them to their target is very hard (looks similar to "just doesn't work")

Bad reasons:

* It's too expensive to prove that a drug works

* It's too difficult to differentiate the patients for whom a drug works and the patients for whom it does not

* It is very hard to predict recruitment and to actually recruit patients for clinical trials

* There aren't enough people with the disorder who are also rich enough to afford treatment to justify development

A lot of potential treatments are too easily available and can't be patented. If a big pharma company can't make massive profit from it, they won't bother bringing it to market. Consider that a not-good reason.

Other treatments may eventually prove to have too many serious negative side effects. That's a good reason to abandon them.

In the early 2010s I had a couple friends working at a biotech startup with a moonshot cancer cure. They had amazing results in animal testing, and had raised just enough funding to do a first human trial on a terminal patient.

That patient was hit and killed by a car two days after finishing their treatment.

Along with the CEO's stubborn refusal to give up any more equity in the company, they went under, and the world will never know if that treatment worked.