ACME Executive

If you’re bothered by allergies every spring, you may pop a Benadryl or Claritin most mornings to make the days tolerable. Two-thirds of Americans report spring allergies, and about 4 in 10 say they take an allergy medication several times a week.

But those medicines, while valuable, don’t exactly fix the problem. One 2001 study in the United Kingdom found 60 percent of people who took some kind of over-the-counter medication for allergies reported they were not satisfied with how it managed their symptoms. 

Nasal sprays are not exactly enjoyable or easy to operate. Allergy medicines have to be taken every day if you deal with serious hay fever, and they can produce, ironically, tiredness for some people during this season of renewal. A missed dose can lead to a day of hacking and sneezing. Oh, and the more you take them, the less likely they are to work.

A century ago, antihistamines were a revolution in allergy treatment. But now, we’re on the cusp of another.

Omalizumab, sold as Xolair, is an asthma medication that was approved more than 20 years ago, but it has proven successful in treating seasonal allergies in recent preliminary trials. So successful, in fact, that now some doctors in the US are prescribing it for certain patients during hay fever season. It is an injection, rather than a pill or a spray, that’s given a couple of weeks before pollen and grass levels start to rise.  

One obvious benefit is you get a single shot and enjoy your spring. But even better, omalizumab can forestall allergic reactions at the source. That means an injection could stop all allergic reactions — not only seasonal allergies but food allergies (such as peanuts) and insect allergies for a prolonged period of time. This class of treatment — monoclonal antibodies, special artificial proteins that carry instructions to the body’s immune system — have the potential to be a genuine all-in-one allergy wonder drug.

“The biggest advantage of antibody-based therapeutics is that they offer the potential to target the underlying pathways driving allergic reactions in general,” said Sayantani Sindher, a clinical associate professor at Stanford University’s Sean N. Parker Center for Allergy and Asthma Research. “This means antibody-based therapies will simultaneously impact all of the patient’s allergens.”

Large clinical trials are underway in China and Japan, which could lead to omalizumab’s approval in those countries for seasonal allergies. The next generation of monoclonal antibody allergy treatments is already in the works. 

How monoclonal antibodies could stop allergy season before it starts

In the United States, the use of monoclonal antibodies started with doctors studying and prescribing preexisting treatments “off label” — meaning these are drugs that were actually developed for something else.

Asthma and seasonal allergies often occur in tandem, which made omalizumab an obvious candidate for a new approach to allergy treatment. The drug had also separately proven effective in treating food allergies, adding to evidence that it had the right properties to stop seasonal allergies at the source.

The treatment has demonstrated significantly better outcomes than antihistamines in small randomized trials, requiring only one dose two weeks before pollen and grass season. A 2022 study reported that patients who received a 300 mg injection of Xolair experienced fewer symptoms and fewer days that required a daily antihistamine or other medication; the patients also reported a better quality of life during the allergy season. Their symptoms were particularly improved during the worst pollen days when compared to the people who only took a daily medication.

When pollen and other allergens emerge every year and enter your body through your eyes, ears, or nose while you’re enjoying the crisp spring air, your body’s immune system overreacts. Immunoglobulin, proteins that are supposed to identify and attack parasites or a virus, instead go after the otherwise harmless allergen. 

When the immunoglobulin attacks the allergen, your body releases histamine, a chemical critical to inflammation (which, again, is really important when you are actually exposed to a dangerous parasite or virus). That inflammation then creates all that mucus and sneezing.

Monoclonal antibodies stop that process before it begins. They deliver artificial proteins that carry instructions to your immune system to block the receptors that create allergic reactions and prevent the overresponse that releases histamine in the first place.

Artificially altered antibodies have been around for decades, with different iterations being developed to respond to new health threats. Monoclonal antibodies were developed for Covid-19 during the pandemic and recently provided the platform for an RSV vaccine. 

Dupilumab (another monoclonal antibody treatment used for skin rashes, asthma, and a lung disease that makes it difficult to breathe called COPD) targets a different receptor but has likewise shown promising results in studies so far. In a large 2018 study, asthma patients who suffer from seasonal allergies received a 300 mg injection every two weeks and showed significant improvements in their nasal blockage. A 2022 study found fewer allergy symptoms among both people with allergic asthma and people without.

Monoclonal antibody injections superficially resemble allergy vaccines, which have been investigated more aggressively in recent years. Those shots as well as oral tablets that work in the same way function differently: They expose people to small amounts of the actual allergen, giving their bodies a chance to develop natural immunity to it. They can unlock more durable resistance to specific allergies — but they can only treat one allergy at a time.

You may also need to go to the doctor once a week for a month or longer during the initial treatment course. Some companies are trying to make them easier to use.

Going forward, the conventional kind of allergy vaccine could still have a place, particularly for patients who are at particularly high risk of developing asthma, by strengthening immune systems for the longer term; monoclonal antibodies, by contrast, do not actually modify the immune system in the same way, so they would need to be taken again periodically.

But Sindher emphasized the potential to treat all allergies at once as an obvious advantage for monoclonal antibodies over immunotherapies.

“Pollen allergy and food allergy are frequently found together,” she said. “Omalizumab has the potential to treat both.”

With monoclonal antibody shots, patients also report fewer side effects. There is a subset of people for whom antihistamines don’t work, including those who have built up a tolerance to those drugs after frequent usage. These new monoclonal antibodies may help them where those old treatments are now failing.

Specially tailored allergy-specific products are now in the works, ushering in this new era of allergy treatment. In early April, the final stage of one clinical trial found the following results after four weeks: Patients who had still reported symptoms after taking the standard-of-care treatment and then received a monoclonal antibody injection were much more likely to report mild or no nasal symptoms (62 percent) than people who were taking the placebo (39 percent). They scored significantly better on oral symptoms and other measures of efficacy without serious side effects. 

The drug in the clinical trial, Stapokibart, was recently approved for seasonal allergy treatment in China, and its developer, Keymed, has premised its business on developing and gaining approval for treatments in that country and then bringing them to the US. Monoclonal antibodies will continue to make inroads as more products come to the market. 

A new era for allergy treatment

Monoclonal antibodies, by offering months of allergy relief in just one injection, could elide one of the biggest challenges in all pharmaceutical treatments: making sure people take medicines like they are supposed to.

With antihistamines and nasal sprays, you must regularly buy them yourself and repeatedly remember to take them correctly to stave off allergy symptoms. That 2001 study in the UK found that many people who suffered seasonal allergy symptoms nonetheless did a poor job of taking medication as they should: Among the 54 percent of people who were experiencing poor allergy symptoms, 70 percent didn’t use the conventional allergy medicines according to the clinical guidelines.

But for allergy sufferers to make the jump from something like Claritin to an annual allergy shot that works even better, health insurance coverage will be critical: The list price on omalizumab is $1,500 a pop. This would be a new cost to health plans because patients often bear their own over-the-counter antihistamine med costs. Off-label coverage of any drug, including omalizumab for seasonal allergies, can be fickle. Some popular plans, such as United Healthcare, are not currently covering the drug for that use at this time because they consider it unproven. 

As more research comes in and more products come on the market, the insurers’ value proposition may change. The FDA recently approved a generic version of omalizumab, which should help reduce prices for that injection. As they do, they could offer more value for the patients for whom conventional therapies aren’t working.

Seasonal allergies can significantly diminish a person’s quality of life — during what should be one of the most enjoyable times on the calendar — and they come around every year. 

The work to provide all-in-one allergy relief isn’t finished yet. But at long last, we are on the precipice of allowing more people to break free from the perennial pollen cycle for good.

Musk Hounded by Haters:

On Saturday Elon Musk sat in his personal jet and tested out Starlink's in-air WiFI by streaming some Path of Exile 2. Less than five minutes into the stream, someone in game chat asked him to "jerk off mr trump so he dies of a heart attack!" For the next hour and 40 minutes, the world's richest man frowned his way through a livestream while people yelled at him.

Path of Exile 2 is an action role-playing game and Musk loves it, but he's terrible at it. He has claimed he's one of the top players in the world and later admitted he's paid people to help keep his account leveled up and full of the high-end gear it needs to play the game at the highest level. [...]

• ELON ARE YOU A SMART FELLA OR A FART SMELLA
• YOU HAVE NO REAL FRIENDS AND WILL DIE ALONE
• STILL NOT OVER GRIMES SHE NEVER LOVED YOU
• YOU WILL ALWAYS FEEL INSECURE IT WILL NEVER GO AWAY
• YOU RUINED THE COUNTRY JUST LIKE YOU RUINED ALL YOUR MARRIAGES

Since Musk is too afraid of serial killers to eat in restaurants where the little people could heckle him and ruin his meal, it's important to take the heckling to his "man cave".

Previously, previously, previously, previously, previously, previously, previously, previously, previously.

On Sunday, a few thousand people in Green Bay, Wisconsin, gathered to hear Elon Musk speak — and give away two giant cardboard checks for $1 million. Attendance at the event was limited to people who had added their names to a petition against “activist judges,” created by Musk’s America PAC. He has promised money and other “surprise announcements” to people who sign the petition, and the splashy million-dollar giveaway ratcheted up the stakes. After their names were announced, winners shuffled onstage to awkwardly accept the prop checks and pause for a photo op with Musk, who has poured tens of millions of dollars into the race for Wisconsin’s Supreme Court seat. 

The checks are Musk’s latest attempt to use his vast wealth to turn out voters ahead of Tuesday’s election. He has promised $100 to voters who sign the “activist judges petition” and micro-earnings for people who hold up a photo of Musk’s chosen candidate with a thumbs-up. The petition and the promises of money are a not-so-subtle way of collecting registered voter data.

It’s the same playbook Musk deployed ahead of the November presidential election that some elections experts say broke the …

Read the full story at The Verge.

If you (or someone you know) has hiked the Appalachian Trail since 1979, it’s likely that a photo of that person exists in the ATC’s online Hiker Photo Archive. Some folks in these photos have never seen them before & forgot they even exist.

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