The Top 7 Craziest Drugs in the Pipeline

Even with a trained eye, watching what is coming through the drug pipeline can get a little boring.

This drug is in that phase III trial; that one had promising phase III results, but probably won’t go anywhere; that third one had to be stopped because it wasn’t working. Every new drug has the potential to be amazing and will likely help someone, but reading through the deluge of New! and Exciting! promises of drugs can be an eyes-glazed-over experience.

After all, as one researcher who studied new drug approvals recently toldDrug Topics, “Most often, we found that new drugs offered marginal improvements, and a surprising number offered no improvement over existing treatments at all.” There are occasional exciting and revolutionary treatments (like the promises offered by CAR-T therapy), but often the pipeline just seems … mundane.

However, if you search through the hundreds of applications claiming to be The Next Great Thing, eventually you stumble onto the strange side of the pipeline; the side with out-there drugs, strange indications, and even weirder development methods. After looking around, we found seven of the weirdest drugs we could find in the pipeline-all of them real (we promise!).

Up next: The FDA weighs in on a party drug

1. MDMA OK Says FDA

Though this sounds like the dream of a stoned-out college kid musing to his friends about what the world would be like without the Man, ecstasy (MDMA, or its approved generic name, midomafetamine) is a very real and serious proposition for the treatment of post-traumatic stress disorder.

How serious is it? The FDA just granted a breakthrough therapy designation to MDMA. The agency is working with the Multidisciplinary Association for Psychedelic Studies (Yes, it is a real organization) to develop Phase 3 trials of MDMA-assisted psychotherapy for patients with severe PTSD. The first trial will begin next spring and involve 200 to 300 patients in the United States, Canada, and Israel.

In Phase 2 trials with 107 patients, after three sessions of MDMA-assisted psychotherapy, 61% of patients no longer had symptoms of PTSD. At a 12-month follow-up, 68% no longer had PTSD. These results have not yet been published, so maybe take them with a grain of salt.

2. Lactose Intolerant No More

Not all drugs can be as glamorous as that breakthrough cancer treatment or miracle orphan drug. Instead, some treat more mundane maladies.

Take RP-G28 (do NOT confuse this with the RPG-28, a Russian hand-held anti-tank rocket launcher), a drug for the treatment of lactose intolerance. The drug, currently in Phase 2b/3 trials, is being developed by Ritter Pharmaceuticals. Lactose intolerance affects over one billion people worldwide.

RP-G28 stimulates the growth of lactose-metabolizing bacteria in the colon, which reduces gas production, which in turn relieves the symptoms of lactose intolerance, some of which are uncomfortable and some of which are less than socially acceptable. According to Ritter, this is the first time researchers have “been able to identify a change in the specific bacteria species as a result of a course of treatment of a specific disease.”

Early phase 2 trials for the drug seem promising; a majority of patients reported no abdominal pain after taking the drug. If approved, RP-G28 would be the first ever FDA-approved drug for the treatment of lactose intolerance (but not the last time bacteria will be mentioned on this list).

3. A Radical New Drug?

Sometimes the hottest new drug is available for $3.99 in the supplement section of your pharmacy. Biotin-formerly known as vitamin H and now called vitamin B₇-is now in phase 3 trials for the treatment of progressive MS. MedDay Pharmaceuticals is currently assessing high-dose biotin.

In one pilot study of 23 patients, 21 patients (91.3%) improved clinically. Four patients with prominent visual impairment related to optic nerve injury “improved significantly.” One patient kept improving from 2 to 16 months following treatment, and 16 patients with prominent spinal cord involvement improved 2 to 8 months following treatment.

There are currently no approved drugs for progressive MS-proving that even the most mundane treatments could provide huge benefits for patients.

4. Putting the Drug Back in Prescription Drugs

Medical marijuana is all the rage these days, but one drug is taking cannabis to a new level. In what again sounds like a stoned college student’s dream, GW Pharmaceuticals is currently testing Epidiolex, an oral solution of pure plant-derived cannabidiol.

The drug is currently in several Phase 3 trials for multiple indications-two trials for Dravet syndrome, two for Lennon-Gastaut syndrome, one for Tuberous Sclerosis Complex, and one for Infantile Spasms.

The FDA has also granted expanded access for Epidiolex, allowing physicians to apply for emergency access to the drug for patients suffering from intractable epilepsy.

5. Didn’t We Eradicate That One?

This drug comes straight from the beginning of B movie. As if the anti-vaccination movement bringing back preventable diseases wasn’t bad enough, researchers at the Duke University Medical Center, Durham, NC, are conducting Phase 2 trials using a re-engineered polio virus. To make matters worse, that virus is combined with the common cold. Were this a B movie, the polio virus would mutate into a large green blob that would terrorize New York. But in the real world, the virus is doing something much better-attacking tumors.

The trials currently underway are examining the effect of recombinant oncolytic poliovirus PVS-RIPO with or without chemotherapy drug lomustine in treating grade IV gliomas. To create the modified virus, researchers replace the internal ribosomal entry site (IRES) with the IRES from the human rhinovirus type 2. The virus is then taken up and replicates in certain tumor cells, eventually causing tumor cell lysis.

So while you could say that researchers are using new techniques to defeat cancer, you could also say that scientists are creating mutant viruses designed to kill. Your call.

6. Like Borrowing a Cup of Sugar

Sometimes drugs are like hot dogs-you can only enjoy them if you don’t know what’s in them. Take Seres Therapeutics’ efforts to bring the first “regulated, clinically approved bacteria-filled pill to treat diseases associated with disruptions to the microbes inside the human body.” They say that yogurt eaters know that bacteria are good-but they might have a harder time selling that their pills are not filled with live yogurt cultures but with live human bacteria.

Seres isn’t saying exactly what bacteria are involved, but do mention fecal transplants as an analogous-though insufficient-treatment. They do, however, say that one drug, SER-109, contains “an ecology of bacterial spores enriched and purified from healthy, screened human donors.” SER-109 is a pill, currently in Phase 3 trials, used for the treatment of recurrent Clostridium difficile Infection (CDI). CDI is, according to the CDC, one of the top three most urgent antibiotic-resistant bacterial threats in the United States and results in 29,000 deaths per year. SER-109 may repair dysbiosis-a disrupted state of the microbiome-an underlying cause of recurrent CDI.

7. Insta-Tan

This one isn’t technically in the pipeline yet, but it’s too odd not to share.

From the lowly cave dwellings of our ancient ancestors to the sleek smart homes of today, humans have spent the last 10,000 years perfecting the indoors. And now there’s one more reason to stay home-researchers at the Massachusetts General Hospital in Boston have developed a process that may eventually give anyone the ability to tan with just a simple application of a liquid.

The researchers bought a molecule that inhibits salt-incuclibe kinase, which turns off melanin production. They then create a compound using that molecule, which they applied to the backs of shaved redhead mice. After 7 days of treatment the skin turned almost black, which then returned to normal within two weeks-with no noted safety concerns. The researchers then modified the compound to penetrate human skin and tested it on discarded patches of skin from surgical procedures. One of the compounds tested made a brown spot, indicating that it was able to reach the melanocytes in the skin and spur melanin production.

The researchers say more work is needed before human trials could begin, but they see the compound as a way to combat skin cancer. The compound would work even on fair-skinned people who do not normally tan, potentially lowering their risk for skin cancer. However, it is not intended to replace sunscreen, but to enhance its effects. The researchers are currently looking for collaborators to test the compound in a clinical trial.