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Merck’s oral cholesterol-lowering drug shows similar efficacy to injectable predecessors as it moves to PhIII: #ACC23

NEW ORLEANS — In back-to-back presentations on Monday with its Phase III data on a drug for pulmonary arterial hypertension, Merck unveiled new mid-stage…

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NEW ORLEANS — In back-to-back presentations on Monday with its Phase III data on a drug for pulmonary arterial hypertension, Merck unveiled new mid-stage data on an oral cholesterol-lowering drug for heart disease.

The 381-person Phase II study tested four doses of Merck’s oral PCSK9 inhibitor ranging from 6 mg to 30 mg in patients with high cholesterol. At the lowest dose, patients saw their cholesterol levels fall by 41% over the eight-week treatment period, while patients at the highest dose saw their cholesterol levels fall by 61%. The data were presented at the American College of Cardiology annual meeting and simultaneously published in the Journal of the American College of Cardiology.

The cholesterol-lowering numbers so far are comparable with currently approved PCSK9 inhibitors — Sanofi and Regeneron’s Praluent, Amgen’s Repatha and Novartis’ Leqvio — which are all administered via injection. The former two slashed list prices by 60% following low uptake, which doctors said was in part due to their high prices and need for prior authorization from insurance. The hope is that Merck’s oral drug could provide a potentially more accessible option for patients, though it is a ways from approval.

Dipti Itchhaporia

“We know that there are patients that either don’t tolerate a statin or when they do tolerate a statin, we may not necessarily get the LDL goal that we want,” Dipti Itchhaporia said in an interview. The former ACC president and chair of cardiovascular health at Hoag Hospital was not involved in the study.

“Adding a PCSK9 is something that I think about all the time, but there are patients that don’t want to do an injectable, so the idea that there could be an oral PCSK9 I think is very exciting,” she continued.

AstraZeneca is also working on an oral PCSK9 inhibitor, though its candidate is in an early-stage test with healthy subjects. Novo Nordisk was also studying an oral option, but announced it dropped the program in November.

Lead investigator Christie Ballantyne of Baylor College of Medicine said he was told around 10 years ago it would be impossible to make an oral PCSK9 inhibitor because of the interactions on its receptor. Merck’s drug is a macrocycle, a type of wonky chemical ring that has seen limited development into oral drugs (though some are trying to change that with new technology).

In the Phase II study, around 80% to 90% of the participants reached their cholesterol reduction goals over the eight-week period, depending on the dose they received, while only 9% did so on placebo.

Eliav Barr

The next step for Merck is a pivotal Phase III trial, though Merck Research Laboratories CMO Eliav Barr declined to specify which dose Merck would be choosing for the trial, saying only that it likely would not be the lowest dose. Itchhaporia noted the cholesterol lowering in the three higher doses looked relatively similar. At 12 mg, participants had their cholesterol levels lowered by 56%, while at 18 mg it was lowered by 59%.

Merck plans on starting the Phase III trial in the second half of the year.

In this study, 39% of participants were taking no statin, 35% were taking low- or moderate-intensity statins, and 26% were taking high-intensity statins. When asked about statin intolerance, Barr said, “While it’s true that there’s a group of patients that are intolerant, or unwilling to take statins, the workhorse for cholesterol lowering around the world is statins and they have been incredibly successful. And so, the role that we see — at present — this drug to have, is the role of being a drug that gets you to goal on top of statins.”

Statin intolerance is a niche Esperion is trying to fill with its drug Nexletol, which it presented long-awaited data for on Saturday at the New Orleans conference. The company is hoping that the new data and potential new cardiovascular risk label for Nexletol will boost the tepid sales of its drug, which was approved three years ago, but Esperion’s stock price $ESPR dropped 21% Monday morning.

In terms of safety for MK-0616, treatment-related adverse event numbers were similar across treatment and placebo groups. The most common adverse events during the study were Covid-19, diarrhea and upset stomach. One patient died during the course of the trial due to a car accident.

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Part 1: Current State of the Housing Market; Overview for mid-March 2024

Today, in the Calculated Risk Real Estate Newsletter: Part 1: Current State of the Housing Market; Overview for mid-March 2024
A brief excerpt: This 2-part overview for mid-March provides a snapshot of the current housing market.

I always like to star…

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Today, in the Calculated Risk Real Estate Newsletter: Part 1: Current State of the Housing Market; Overview for mid-March 2024

A brief excerpt:
This 2-part overview for mid-March provides a snapshot of the current housing market.

I always like to start with inventory, since inventory usually tells the tale!
...
Here is a graph of new listing from Realtor.com’s February 2024 Monthly Housing Market Trends Report showing new listings were up 11.3% year-over-year in February. This is still well below pre-pandemic levels. From Realtor.com:

However, providing a boost to overall inventory, sellers turned out in higher numbers this February as newly listed homes were 11.3% above last year’s levels. This marked the fourth month of increasing listing activity after a 17-month streak of decline.
Note the seasonality for new listings. December and January are seasonally the weakest months of the year for new listings, followed by February and November. New listings will be up year-over-year in 2024, but we will have to wait for the March and April data to see how close new listings are to normal levels.

There are always people that need to sell due to the so-called 3 D’s: Death, Divorce, and Disease. Also, in certain times, some homeowners will need to sell due to unemployment or excessive debt (neither is much of an issue right now).

And there are homeowners who want to sell for a number of reasons: upsizing (more babies), downsizing, moving for a new job, or moving to a nicer home or location (move-up buyers). It is some of the “want to sell” group that has been locked in with the golden handcuffs over the last couple of years, since it is financially difficult to move when your current mortgage rate is around 3%, and your new mortgage rate will be in the 6 1/2% to 7% range.

But time is a factor for this “want to sell” group, and eventually some of them will take the plunge. That is probably why we are seeing more new listings now.
There is much more in the article.

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Pharma industry reputation remains steady at a ‘new normal’ after Covid, Harris Poll finds

The pharma industry is hanging on to reputation gains notched during the Covid-19 pandemic. Positive perception of the pharma industry is steady at 45%…

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The pharma industry is hanging on to reputation gains notched during the Covid-19 pandemic. Positive perception of the pharma industry is steady at 45% of US respondents in 2023, according to the latest Harris Poll data. That’s exactly the same as the previous year.

Pharma’s highest point was in February 2021 — as Covid vaccines began to roll out — with a 62% positive US perception, and helping the industry land at an average 55% positive sentiment at the end of the year in Harris’ 2021 annual assessment of industries. The pharma industry’s reputation hit its most recent low at 32% in 2019, but it had hovered around 30% for more than a decade prior.

Rob Jekielek

“Pharma has sustained a lot of the gains, now basically one and half times higher than pre-Covid,” said Harris Poll managing director Rob Jekielek. “There is a question mark around how sustained it will be, but right now it feels like a new normal.”

The Harris survey spans 11 global markets and covers 13 industries. Pharma perception is even better abroad, with an average 58% of respondents notching favorable sentiments in 2023, just a slight slip from 60% in each of the two previous years.

Pharma’s solid global reputation puts it in the middle of the pack among international industries, ranking higher than government at 37% positive, insurance at 48%, financial services at 51% and health insurance at 52%. Pharma ranks just behind automotive (62%), manufacturing (63%) and consumer products (63%), although it lags behind leading industries like tech at 75% positive in the first spot, followed by grocery at 67%.

The bright spotlight on the pharma industry during Covid vaccine and drug development boosted its reputation, but Jekielek said there’s maybe an argument to be made that pharma is continuing to develop innovative drugs outside that spotlight.

“When you look at pharma reputation during Covid, you have clear sense of a very dynamic industry working very quickly and getting therapies and products to market. If you’re looking at things happening now, you could argue that pharma still probably doesn’t get enough credit for its advances, for example, in oncology treatments,” he said.

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Q4 Update: Delinquencies, Foreclosures and REO

Today, in the Calculated Risk Real Estate Newsletter: Q4 Update: Delinquencies, Foreclosures and REO
A brief excerpt: I’ve argued repeatedly that we would NOT see a surge in foreclosures that would significantly impact house prices (as happened followi…

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Today, in the Calculated Risk Real Estate Newsletter: Q4 Update: Delinquencies, Foreclosures and REO

A brief excerpt:
I’ve argued repeatedly that we would NOT see a surge in foreclosures that would significantly impact house prices (as happened following the housing bubble). The two key reasons are mortgage lending has been solid, and most homeowners have substantial equity in their homes..
...
And on mortgage rates, here is some data from the FHFA’s National Mortgage Database showing the distribution of interest rates on closed-end, fixed-rate 1-4 family mortgages outstanding at the end of each quarter since Q1 2013 through Q3 2023 (Q4 2023 data will be released in a two weeks).

This shows the surge in the percent of loans under 3%, and also under 4%, starting in early 2020 as mortgage rates declined sharply during the pandemic. Currently 22.6% of loans are under 3%, 59.4% are under 4%, and 78.7% are under 5%.

With substantial equity, and low mortgage rates (mostly at a fixed rates), few homeowners will have financial difficulties.
There is much more in the article. You can subscribe at https://calculatedrisk.substack.com/

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