It's that "not many negative effects" thing that's the joker in the deck.
Lithium, which PALS were clamoring for after early trials, subsequently proved no more effective than placebo, with more adverse events in ALS than in psychiatric disorders. Multiple trials were stopped early due to a negative risk/benefit ratio.
Years later, the FDA approved diaphragm pacing in the "what harm can it do" spirit, but subsequently it more often accelerated than slowed ALS progression.
There are other examples. Anything strong enough to help motor neurons has a potential down side. And the R drugs appear to have pretty narrow time windows/patient profiles for optimal efficacy, meaning that for some people the risks and logistics may not justify use, whether reimbursable or not.
We frequently discuss approaches here that have stronger evidence of safety and efficacy than any ALS drug on the market. From BiPAP to feeding tubes (if what you put in the tube isn't junk), to social interaction and the right mobility device(s), the curve of this disease is being bent and will continue to be.
Many other fatal illnesses/injuries are actually more heterogeneously expressed than is ALS. But uncertain recruitment, the vagaries of the FRS, and a hostile reception to biopharmas who cannot provide (for many good reasons) early access, are not strong incentives to jump in the pool.
Best,
Laurie
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