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Clinical trials are the make or break stage for new pharmaceuticals, and unfortunately, most break — 90% of drugs that reach human trials fail, mainly because animal models just aren’t a great predictor of how a drug will work in people.
Within the remaining 10%, though, are treatments that could be life changing — or even life-saving — for huge numbers of people. In 2023, researchers reported the promising results of several clinical trials that could change medicine and save lives. Here are five of the biggest.
Curing high cholesterol with CRISPR
High levels of “bad” LDL cholesterol in your blood cause plaque to build up in your arteries, leading to cardiovascular disease, heart attacks, and strokes. It is the biggest contributor to the number one cause of death in the world.
Daily pills can help lower cholesterol, but they can also cause side effects, and for some people, even these drugs can’t get their LDL to safe levels. Dietary and lifestyle changes can help, too, but most people have a tough time committing to them.
Boston-based biotech firm Verve Therapeutics is developing a new kind of cholesterol treatment, called VERVE-101. It uses CRISPR to deactivate a gene in the liver that controls the production of PCSK9, a protein that prevents the removal of excess LDL cholesterol from the body.
For a first-in-human trial, Verve administered varying doses of the therapy to 10 people born with a genetic condition that leads to extremely high LDL levels. They were in the late stages of severe heart disease, and not even high-dose statins could keep their LDL at acceptable levels.
According to interim trial data shared in November, one dose of VERVE-101 was able to reduce their cholesterol levels by as much as 55% and keep them low through 6 months of follow-up.
Though the trial was small and raised some safety concerns (two participants had heart attacks during it), the results are an encouraging sign that a one-and-done treatment for high cholesterol could be within our reach.
More than just weight loss
In 2021, the FDA approved the diabetes drug semaglutide (brand name Wegovy, made by Danish pharma company Novo Nordisk) as a weight-loss treatment for people with obesity. It also approved the weight-loss drug for people who are overweight and have another related condition, such as high cholesterol or high blood pressure.
Being overweight or obese increases your risk of diabetes, heart disease, death, and more, so a drug that helps people shed excess pounds could be a huge boon to public health — but getting semaglutide hasn’t been easy for many.
That’s because weight-loss drugs are considered “lifestyle” medications, and Medicare and private insurance companies typically don’t cover those. That has meant the only option for some is to pay out of pocket, but a single month’s worth of Wegovy can cost as much as $1,350, and if you stop taking the drug, you’re likely to regain any weight you lost while on it.
But in November 2023, Novo published the results of its huge phase 3 SELECT trial, which found that semaglutide reduced the risk of heart attacks, strokes, and death from heart disease by 20% over four years, in a trial population that was overweight or obese and had a history of heart disease without diabetes. The group that got semaglutide also had a 19% lower risk of death, from any cause, compared to the placebo group.
Novo has asked the FDA to update the label for Wegovy to include the reduced risk of these serious medical events, and if the agency agrees, the move could encourage insurers to start covering the weight-loss drug, making it more accessible to those who could use it.
A long-awaited vaccine
Respiratory syncytial virus (RSV) is a common bug, and most people infected by it feel like they have a bad cold — they cough, sneeze, have a headache, and just want to stay in bed for a few days before recovering.
In vulnerable people, though, RSV can lead to serious, potentially fatal lower respiratory tract diseases (LRTDs), such as pneumonia and bronchiolitis. Seniors and children are at high risk of these severe infections — every year in the US, 6,000 to 10,000 seniors die from an RSV infection, and 58,000 to 80,000 children under the age of 5 are hospitalized due to one.
That could soon change thanks to the approval of the first RSV vaccines this year.
The FDA approved GSK’s RSV vaccine on May 7 — making it the world’s first RSV vaccine.
In February 2023, UK drugmaker GSK published the results of a phase 3 trial of Arexvy, an RSV vaccine designed to prevent infection in seniors. During the trial, it reduced the risk of an RSV-caused LRTD by 83% and a severe RSV-caused LRTD by 94% in people over the age of 60 in their first RSV season after vaccination.
Then, in April, Pfizer published data from its own phase 3 RSV vaccine trial. In the first RSV season after vaccination, that shot, ABRYSVO, was 67% effective at preventing an RSV-caused LRTD with two or more symptoms in people 60 years and older and 86% effective at preventing an infection with three or more symptoms.
To see if ABRYSVO could help infants avoid severe RSV infections, Pfizer conducted another trial in which it administered the shot to pregnant people. Data from that trial, also published in April, revealed the vaccine was 82% effective at preventing the infants of those vaccinated from having to see a doctor for a severe RSV-caused LRTD during their first RSV season.
Based on these clinical trials, the FDA approved GSK’s RSV vaccine on May 7 — making it the world’s first RSV vaccine. It approved Pfizer’s vaccine for seniors on May 31 and for pregnant people on August 21, offering protection to all the most at-risk groups.
Vertex’s new painkiller
Prescription opioids, such as oxycodone and morphine, are highly effective at treating both chronic and severe acute pain. However, they’re also addictive and widely abused — in 2021, nearly 17,000 Americans died of an overdose involving prescription opioids — and they come with side effects that can make them hard to tolerate.
Vertex Pharmaceuticals is currently conducting clinical trials of an opioid alternative that relieves pain by interfering with NaV1.7, a protein involved in the brain’s processing of it, which is different from how opioids work.
In August 2023, the company published the results of a phase 2 trial that tested the ability of the medication, called VX-548, to relieve acute pain in people who’d just undergone abdominoplasty (“tummy tuck”) or bunionectomy surgeries. It found that the drug outperformed a placebo without causing serious side effects.
Then, on December 13, Vertex announced the results of another phase 2 trial in which VX-548 was administered to people with diabetic peripheral neuropathy (DPN), a type of painful nerve damage caused by diabetes.
After 12 weeks of treatment, participants reported statistically significant pain relief compared to at the start of the trial, and again, side effects were mild to moderate. The reduction in pain was also slightly greater in those treated with VX-548 than in a comparison group given pregabalin, an FDA-approved non-opioid nerve pain reliever.
While Vertex’s clinical trials didn’t test how the drug compares to opioids at relieving pain, the fact that this new approach works at all is encouraging. Vertex is already conducting phase 3 studies for acute pain relief and another phase 2 trial for a type of chronic nerve pain caused by back injuries.
A better flu shot
The approval of Moderna’s and Pfizer/BioNTech’s COVID-19 vaccines proved that mRNA shots could be safe and effective, and today, researchers are trialing mRNA-based vaccines to prevent everything from herpes to cancer.
While it’s too soon to predict which of those vaccines (if any) will be approved first, shots to prevent the flu are a solid bet given that we already know it’s possible to vaccinate against the flu virus and there’s a huge market for a better flu shot.
In October 2023, Pfizer shared top-line data from a phase 3 trial of an in-development mRNA flu vaccine (PF-07252220), revealing that the shot performed as well as a licensed flu vaccine at preventing symptomatic flu in 18 to 64 year olds, though it didn’t trigger as robust of an immune response as hoped against influenza B, which accounts for less than 25% of flu cases.
Moderna, meanwhile, delivered an update on its ongoing phase 3 trial of an mRNA flu vaccine in September, reporting that the shot had triggered a more robust immune response than a licensed flu vaccine against both influenza A and B.
Clinical trials of both mRNA flu vaccines are ongoing, and even if they prove to be merely equally effective to the shots we have now, they could still be a boon for public health.
Because mRNA vaccines don’t take as long to manufacture, we could wait until later in the year to choose a flu strain to target, potentially increasing our chances of efficacy each flu season. It’s also easier to make a lot of mRNA shots than existing flu vaccines, which could allow us to vaccinate more people, more quickly in the event of a future flu pandemic.
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