Month: July 2024

NewAmsterdam’s Obicetrapib Slashes HeFH LDL-C in First Phase 3 Trial

Posted on by Jake Fishman

Topline results are in from NewAmsterdam Pharma’s BROOKLYN study, showing that obicetrapib safely and effectively reduces LDL cholesterol in patients with heterozygous familial hypercholesterolemia (HeFH) who can’t be effectively treated by current cholesterol drugs.

  • Obicetrapib is an once-daily oral medication that inhibits the CETP protein to reduce LDL-C levels and potentially decrease cardiovascular risks.
  • The drug achieved solid LDL-C reductions in previous studies, and is now the focus of four pivotal trials, starting with the BROOKLYN study.

The Phase 3 BROOKLYN trial evaluated 10 mg obicetrapib in 354 randomized HeFH patients whose LDL-C wasn’t adequately controlled despite taking maximally tolerated lipid-lowering therapy. 

The results appeared quite positive for obicetrapib, which… 

  • Achieved a 36.3% LDL-C reduction after 84 days (the primary endpoint), and maintained a 41.5% reduction through one year.
  • Reduced 51% of patients’ LDL-C levels below 70 mg/dl.
  • Drove significant reductions in HDL-C, non-HDL-C, Lp(a), and Apo(B).
  • Was well-tolerated, with safety results comparable to placebo, no increases in blood pressure, and lower treatment discontinuation rates (7.6% vs. 14.4%).

Despite these improvements, obicetrapib’s LDL-C reductions in the BROOKLYN study fell short of its previous Phase 2 trial that achieved a 51% average reduction when taken alone, driving NewAmsterdam’s stock price down 28%. 

  • However, the BROOKLYN patients were already on maximum lipid lowering meds (14% on PCSK9I, 54% on Ezetimibe + HI statin), potentially skewing the trial’s LDL-C reductions.

Either way, these results make obicetrapib’s three other pivotal Phase 3 studies even more high stakes. The BROADWAY, TANDEM, and PREVAIL trials will use obicetrapib alone or with other lipid-lowering drugs across a range of patients, while evaluating cholesterol reduction or cardiovascular outcomes.

The Takeaway

NewAmsterdam still has a long way to go to prove obicetrapib’s value in the crowded lipid-lowering arena, but the BROOKLYN trial is a solid step towards that goal. 

It might not have met Wall Street’s LDL-C expectations, but these results seem like good news for the estimated 1.33 million Americans with HeFH, and NewAmsterdam’s wave of forthcoming studies should paint a much clearer picture of how obicetrapib can help an even wider range of patients.

Edwards Acquires JenaValve and Endotronix, Expands into Aortic Regurgitation and Heart Failure

Posted on by Jake Fishman

Edwards Lifesciences is going all-in on structural heart and heart failure, acquiring aortic valve-maker JenaValve Technology and implantable heart failure monitor company Endotronix for $1.2B and up to $445M in milestone payments.

These two acquisitions could impact Edwards’ structural heart and heart failure portfolios in unique and meaningful ways…

JenaValve’s Trilogy TAVR system doesn’t yet have FDA approval, but is CE Marked for both aortic regurgitation and aortic stenosis, which is notable given that all other TAVR systems only address aortic stenosis.

  • The JenaValve Trilogy could gain FDA approval for aortic regurgitation by late 2025, complementing Edwards’ already strong aortic stenosis capabilities.

Endotronix recently landed FDA approval for its Cordella heart failure sensor, which combines an implanted PA sensor to measure congestion, a handheld PA pressure reader, and a digital health platform to enable comprehensive home-based HF management. 

  • The Cordella system could have a major impact, given the success of its PROACTIVE-HF trial, and its anticipated nationwide coverage by CMS in early 2025.

These acquisitions also confirm that Edwards is in the middle of an M&A spree, as they come just a few weeks after it acquired early-stage TMVR company Innovalve Bio Medical for $300M and invested $16M in surgical mitral valve startup Affluent Medical.

In fact, Edwards likely has more M&A coming up, noting that it just sold its Critical Care business to BD for $4.2B, pledging to use the influx of capital to “to fund strategic growth investments” targeting structural heart, pulmonology, and interventional heart failure technologies.

Although these recent acquisitions aren’t expected to have a major impact on Edwards’ finances until at least 2026, their success is crucial in the long term, noting that Edwards just reported a slowdown in its flagship TAVR business that sent the stock plummeting 31%.

The Takeaway

Edwards made it clear that it was going to use its Critical Care cash to drive strategic growth, and it hasn’t taken long to put that plan into action, acquiring its way into key growth areas for the company and the overall cardiac device segment.

Magenta Medical Adds $105M, Targets MCS Disruption

Posted on by Jake Fishman

Israeli heart pump startup Magenta Medical wrapped up a $105M financing round to advance clinical programs supporting its Elevate left ventricular assist device, a percutaneous heart pump that Magenta believes could disrupt the mechanical circulatory support (MCS) segment.   

The miniature Elevate device is folded and delivered percutaneously through the femoral artery (8 Fr inner diameter, 10 Fr sheath), passing through the aorta and aortic valve, before self-expanding in patients’ hearts where it controls blood flow (surpassing 5 L/min of mean flow, 8L/min peak).

  • Elevate would become the world’s smallest heart pump, and the most powerful transcatheter pump, even smaller/stronger than Abiomed’s Impella (9 Fr, 4-6 L/min flow).
  • More importantly, it could make the Elevate pump applicable to all MCS conditions, eliminating the need for device escalations and unnecessary/invasive surgical replacements.

That potential has helped Magenta raise over $200M across five rounds so far, including a $55M round in May 2023, which have funded the Elevate pump’s mounting clinical evidence:

The new funding will now support Magenta’s U.S. clinical programs across a range of MCS indications, and its efforts to seek FDA approval for patients undergoing high-risk PCIs (with other indications likely coming after).

You can see why Magenta and its VC investors are bullish, considering the device’s smallest/strongest credentials, the heart pump market’s projected growth, Magenta’s co-founders’ track record (their previous heart valve startup sold to Medtronic for $350M), and Abiomed’s massive $16.6B acquisition by J&J.

  • Even Abiomed, who most view as Magenta’s primary heart pump competitor, was an early investor in Magenta Medical back in 2017. 

The Takeaway

Although Magenta Medical still has a lot to prove, and its path towards commercial adoption is unlikely to be straightforward, the Elevate pump’s potential to disrupt the MCS market makes this small and mighty device worth keeping an eye on.

The Psychological Impact of AFib Wearables

Posted on by Jake Fishman

AFib patients are increasingly using consumer wearable devices for symptom monitoring, but a new JAHA study suggests that these devices’ often-publicized healthcare benefits are offset by their negative impacts on patient anxiety and healthcare overuse.

The researchers analyzed 9-month EHR records of 172 propensity‐matched patients with AFib (avg. age: 72), including 83 who used wearable devices (mainly Apple Watch or Fitbit), finding that wearable users…

  • Consistently tracked their biometrics, including 45% who checked their heart rate or ECG daily, versus 19% who only checked in response to cardiac symptoms.
  • Reported high rates of “intense fear and anxiety” (20% of users) or “always feeling anxious, scared, or concerned” (15% of users).
  • Commonly contacted their doctor after receiving a “possible AF” notification, including 20% who “always” notified their doc.
  • Were far more concerned about the efficacy of their AF treatments (QoL treatment concern scores: 77.71 vs. 84.11)

As a result, the wearable patients used far more AF-specific health care resources (mean uses: 4.05 vs. 2.7), including more outpatient clinic visits (2.04 vs. 1.33) and more rhythm‐related diagnostic tests and procedures (1.84 vs. 1.00) over the 9 months. 

  • That includes ECGs (P=0.003), echo exams (P=0.04), and ablation procedures (P=0.03). 

The wearable users were also significantly more likely to use informal health care resources such as portals and messaging (5.52 vs. 3.90), sending far more messages to providers (3.59 vs. 2.41) and receiving twice as many responses.

Some might be tempted to chalk this up to the attributes of people who choose to use wearables, but the two groups didn’t differ in education, socioeconomics, AF status/history, or psychiatric status/history.

  • In other words, it could be that merely using a wearable is more likely to make AF patients anxious about their conditions, preoccupied with their device metrics, and more likely to seek and receive care.

The Takeaway

Whether clinicians like it or not, wearables are playing a growing role in their patients lives, sometimes helping with early detection, while apparently risking their psychological wellbeing and driving more healthcare use.

As a result, clinicians will likely have to build their expertise in directing care for wearable-detected AFib abnormalities, and helping their patients deal with the psychological aspects of having all this information literally within arms reach.

Lexeo LX2006 Shows Promise for Friedreich’s Ataxia Cardiomyopathy

Posted on by Jake Fishman

Lexeo Therapeutics gave the 5,000 Americans with Friedreich’s ataxia cardiomyopathy reason for optimism, publishing early results that suggest its LX2006 gene therapy could be able to treat FA cardiomyopathy.

  • Friedreich’s ataxia (FA) is a neurodegenerative disorder caused by loss of function mutations in the frataxin gene, although FA patients generally die from FA cardiomyopathy. 
  • FA is currently only treated by Biogen’s Skyclarys, which slows neurological symptom progression, but doesn’t treat FA cardiomyopathy.
  • LX2006 is designed to promote frataxin protein expression and restore mitochondrial function in myocardial cells, potentially treating FA cardiomyopathy.

The analysis combined data from Lexeo’s SUNRISE-FA Phase 1/2 clinical trial and a Weill Cornell Phase 1A trial that were designed to evaluate whether LX2006 could improve FA-related cardiac dysfunction. 

Based on interim 6-to-18-month data from eight participants, LX2006 led to improvements to…

  • Left ventricular mass index – Of the participants with elevated LVMI at baseline (n=6), four achieved 11.4% average LVMI reductions at 12 months, while two showed 18.3% average reductions at 18 months.
  • Left ventricular lateral wall thickness – Participants with LV wall thickening (n=6) achieved a 13.6% average wall thickness reduction at 12 months.
  • High-sensitivity Troponin I levels – Participants with elevated hsTnI (n=5) achieved a 53.3% average reduction at 12 months.
  • Frataxin levels – All tested patients (n=5) showed increased frataxin levels in their myocardial biopsies following treatment.

LX2006 was also well tolerated in both studies, with no treatment-related serious adverse events and no discontinuations.

  • However, LX2006 might have a limited impact on cardiorespiratory fitness, improving participants’ V02 max levels by just 1% at 12 months and 4% after 12 months.

Lexeo will now advance LX2006 to its third dose cohort, with company execs suggesting that a “higher dose cohort could achieve higher protein levels,” and stating that LX2006 could achieve an accelerated approval due to the lack of FA cardiomyopathy treatments.

  • They do have a point: the FDA has recently shown support for other gene-based treatments of rare conditions and LX2006 gained FDA Fast Track Designation in April.

However, even with this evidence and precedent, a Wall Street sell-off drove a 36% drop in Lexeo’s stock price since last Friday, due to the limited cardiorespiratory evidence and what some people view as another case of Wall Street “selling on the news.”

The Takeaway

Although Lexeo still has plenty to prove (scientifically and financially), these results suggest that the first Friedreich’s ataxia cardiomyopathy treatment might be on the horizon.

Baylor St. Luke’s Settles Concurrent Cardiac Surgery Case

Posted on by Jake Fishman

Cardiac surgeon compensation is generally a numbers game – the more procedures you do, the more you make. However, a Medicare fraud settlement featuring some of Houston’s most prominent institutions and cardiac surgeons reveals the pitfalls of this incentive structure.

Allegations claim that between 2013 to 2020 three decorated Baylor St. Luke’s heart surgeons regularly operated in two to three rooms simultaneously, while “delegating key aspects of extremely complicated and risky heart surgeries to unqualified medical residents.”

  • Each of the surgeons claimed in medical records that they were present throughout the procedures, even if they weren’t.

Since getting flagged by a whistleblower in 2019, the U.S. District Attorney’s office decided that this amounted to Medicare fraud.

Baylor St. Luke’s Medical Center and Baylor College of Medicine finally settled the case for $15M last month, representing the largest settlement ever involving concurrent surgeries, while awarding $3M to the whistleblower (St. Luke’s previous director of transplant surgery).

Although charges against the surgeons were dismissed as part of the settlement, and the defending parties still attest that they followed all laws, the details from the case were alarming…

  • The three physicians performed over 5,000 simultaneous surgeries that generated $150M for the hospital.
  • The physicians achieved four-times higher compensation than the average cardiac surgeon in Houston, and two-to-four times higher procedure volumes than the average U.S. cardiac surgeon.
  • The most prolific surgeon earned over $2M in a year, and was once scheduled to perform 32 hours of surgery over a 16-hour period.
  • These simultaneous operations led to longer procedure and anesthesia times, and involved at least four patient deaths, cases of redo surgeries, and other adverse events.

This settlement is yet another sign that the HHS-OIG is cracking down on Medicare fraud, following a number of other notable cardiology cases that were also tipped off by whistleblowers.

The Takeaway

Given current workloads and incentives, you can bet that Baylor St. Luke’s isn’t the only teaching hospital where cardiac surgeons are treating multiple patients simultaneously. In fact, there’s probably some physicians reading this who believe they could treat multiple patients without sacrificing patient care. 

However, there could be some potential whistleblowers reading this too… and given the message sent by Baylor St. Luke’s massive settlement and whistleblower payout, extreme cases of concurrent cardiac surgeries might soon become a thing of the past.

Nearly Half of American Counties Don’t Have Cardiologists

Posted on by Jake Fishman

If it seems like your patients are coming from a lot further away these days, that might because nearly half of U.S. counties don’t have a single cardiologist working there.

Researchers from Brigham and Women’s Hospital teamed up with GoodRx to analyze data from all 3,143 counties in the US, finding that 46.3% of U.S. counties don’t have a single cardiologist, and this regional cardiologist imbalance often results in…

  • Much Longer Patient Drives – The 22M people who live in these “cardiology desert” counties have to drive an average of 87.1 miles round trip to see their cardiologist, versus just 16.3 miles for patients who live in counties with cardiologists. 
  • Exacerbated Inequalities – Unsurprisingly, 86.2% of those cardiologist-less counties are rural, where patients tend to be poorer and sicker. In fact, patients in no-cardiologist counties had 31% higher CV risk index scores (2.8 vs. 2.1) and worse access to healthy foods (7.2 vs. 7.6 scores).
  • Urban Physician Density – Counties with cardiologists have an average of 24 local cardiologists, although 10% of those counties had just one cardiologist (who is likely overworked).
  • PCP Pressure – The rural cardiologist shortage also places more responsibility on primary care physicians, although cardiologist-less counties also have far fewer PCPs than counties with cardiologists (40.8 vs. 63.2 per 100k residents).

The authors believe that cardiology care’s rural/urban divide is growing wider, and clearly show that it’s having a major impact on outcomes, since cardiologist-less counties had higher age-adjusted cardiovascular mortality rates versus counties with cardiologists (281 vs. 269 per 100k adults) and one year shorter life expectancy.

The solution? The authors highlight digital health’s potential to bridge geographic gaps to cardiovascular care, but also endorse incentivizing more clinicians to practice in rural areas, and better integrating cardiovascular care with primary care (especially regarding CVD prevention and risk modification).

The Takeaway
This is far from the first time that we’ve covered rural America’s problems with cardiovascular care and access, and identifying a problem is a key step towards solving it. However, this latest data suggests that big changes will have to happen before we see meaningful improvements to rural cardiovascular care.

Older Patients and Asymptomatic Valvular Heart Disease

Posted on by Jake Fishman

A new study out of the UK found that over a quarter of people aged 60+ have asymptomatic valvular heart disease, and revealed that prevalence increases as patients age — potentially providing new reasons to screen older patients for VHD.

  • VHD diagnosis generally involves echo exams, ordered in response to patient symptoms or abnormal cardiac auscultation.
  • However, this practice leaves many older patients with undetected VHD, raising interest in using echocardiography as a large-scale VHD screening tool.

To test that theory, researchers performed echo exams on 4,237 asymptomatic 60-and-over adults between 2007 and 2016, finding that…

  • A whopping 28.2% of participants had VHD
  • 2.4% of the VHD cases were clinically significant, including 94 moderate cases and 7 severe cases.
  • Significant VHD prevalence increased with age: 1.5% at 60-64yrs, 2.1% at 70-74yrs, 3.8% at 75-79yrs, and 10% at 85+.
  • The most common VHD cases were tricuspid (13.8%), mitral (12.8%), and aortic (8.3%) regurgitation.

Perhaps most actionable, age was the only factor associated with severe VHD (odds ratio: 1.07 per year), with the number of echo scans required to diagnose one clinically significant VHD case falling from 42 scans among 60-74yr olds to 15 scans among 75-and-over patients. 

Age-targeted VHD echo screening might result in even more positive cases in the real world, noting that only 8.6% of this study’s population was ≥80 years old, and other studies have found 51% prevalence of any VHD among over-65 patients and 17% prevalence of moderate-to-severe VHD among 80-and-over patients.

The Takeaway

By 2050 the over-60 population is expected to double, while the over-80 population triples. That elderly population surge will apparently come with a similar surge in undiagnosed VHD cases, unless there’s big changes to how we screen for VHD.

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