Benzos and pregnancy

Women should probably avoid taking benzodiazepines while they’re pregnant. Why? Looking at the data for almost 2 million women (and 3 million pregnancies), Taiwanese researchers found that there was a notable increase in the risk of miscarriage — 69% higher than women who didn’t take benzos.

The authors wrote, somewhat unnecessarily, “These findings suggest that caution is warranted when using benzodiazepines during early pregnancy.” Indeed.

Here come the price hikes

2024 is almost upon us, and you know what that means: Drug price hikes!

Drugmakers including Pfizer, Sanofi and Takeda Pharmaceutical plan to raise prices in the United States on more than 500 drugs.

Part of that is because of inflation, although that’s only been about 3%. Part is “because we can.” Part is because they’re going to have to cut prices on insulin. And part is because they know that they’re going to have to negotiate prices on 10 drugs starting in September.

(As much as we’re willing to take them to task, even when inflation was high a couple of years ago, pharma companies still kept annual increases to below 10%, and an average of 5% overall. So kudos where they’re due.)

But wait! Other companies are lowering prices. GlaxoSmithKline is planning price cuts for on some asthma, herpes, and anti-epileptic drugs, and then there are those insulin price cuts (although that’s kind of because they have to now).

Cholesterol vaccine?

Sure, statins and PCSK9 inhibitors are great for lowering LDL cholesterol, but why not take it a step further? That’s what University of New Mexico researchers did, creating a vaccine that gets your body (well, the bodies of mice and monkeys) to attack PCSK9 itself.

How, you ask? They “stuck tiny pieces of the PCSK9 protein to the surface of [non-infectious] virus particles” :

“So your immune system makes a really strong antibody response against this protein that’s involved in controlling cholesterol levels. In the animals that we vaccinated, we see strong reductions in cholesterol levels — up to 30%.”

They’ve actually been working on this for 10 years (!) and are now hoping to start human trials. The goal, said the lead researcher, is to have a cholesterol vaccine available within 10 years at less than $100 per dose.

(The one question that wasn’t addressed is whether this is a once-and-done shot, or something that has to be taken regularly. I guess we’ll know in 2034.)

Bonus: Yes, it’s a “game-changer”!

Could oral peptides be coming?

We wouldn’t ask if the answer wasn’t Yes. The thing about peptides is that they have to be injected — the large molecules tend to fall prey to the acid bath that is the human gut.

But Swiss researchers say they’ve developed a cyclic peptide that can be taken orally without being shredded by the digestive system.

The first step was, of course, obvious: “synthesizing linear peptides and subjecting them to cyclization so they formed ring-like chemical structures connected by a metabolically stable thioether (carbon-sulfur-carbon) bond.”

Naturally.

Then came a bunch more science, with the result being “a comprehensive library of 8,448 cyclic peptides” that were small enough to be absorbed by the body before being destroyed.

They showed an oral bioavailability of up to 18%, meaning that 18% of the drug entered the bloodstream and had a therapeutic effect when administered orally. While it might not sound particularly impressive, consider that orally administered cyclic peptides generally show a bioavailability of below 2%.

So that’s the major step — creating small, tough peptides. Next up will be using the technique to target more diseases. “They’re confident they can develop orally administered cyclic peptides for at least some of them.”

Omadacycline beats vancomycin for C Diff

So there’s a new antibiotic called omadacycline that’s based on good ol’ tetracycline. But only now did someone think to see how well it would work against Clostridioides difficile, the bacteria that causes a lot of hospital-acquired infections.

That someone was a University of Houston pharmacist researcher, and he found something surprising: Not only did omadacycline work a treat against C. diff, but it worked better than the current last-line of defense, vancomycin.

Omadacycline was well tolerated by patients, but the key was that it “caused a distinctly different effect on the microbiome than Vancomycin” — it didn’t hurt the beneficial gut microbes nearly as much as vancomycin does, which allowed the good gut bacteria to maintain a resistance to C. diff. (Vancomycin often doesn’t kill enough of the bacteria, so it bounces back.)

Says he: “I would hope that this becomes a normal part of the antibiotic drug development process.”