Lexicon, BridgeBio, Esperion, Pfizer, More Celebrate Wins at 71st ACC Meeting

 

The 71st annual American College of Cardiology’s Scientific Session saw several wins over the weekend – and some “mehs” led by some of biopharma’s largest companies. We take a look at a few of them below:

Lexicon’s Sotagliflozin Victorious Against Stroke, Heart Attacks 

Lexicon Pharmaceuticals shared positive data from its Phase III SCORED study on sotagliflozin in reducing cardiovascular death, non-fatal stroke and non-fatal myocardial infarction compared to simply using a placebo. The drug’s ability to lower risk applies whether or not the patient is diagnosed with cardiovascular disease or does not have any. 

The SCORED trial involved 10,584 participants who received either sotagliflozin or a placebo in addition to the standard of care. The patients had type 2 diabetes and were at risk for cardiovascular disease and chronic kidney disease with an eGFR of 25 to 60 ml per minute for every 1.73 sqm of body-surface area. The primary endpoint was the total number of events involving death from CV illnesses, hospital admissions due to heart failure and urgent care visits for heart failure. Key secondary endpoints were the total number of events from non-fatal stroke, non-fatal MI and cardiovascular causes. 

“We continue to present results showing consistent benefits of sotagliflozin across a wide range of cardiovascular measures,” said Craig B. Granowitz, MD, Ph.D., the senior vice president and chief medical officer of Lexicon. “We remain focused on our goal of making sotagliflozin available for the millions of people suffering from heart failure.” 

Cytokinetics’ Heart Failure Drug Fails to Improve Exercise Capacity

Full results from Cytokinetics‘ Phase III METEORIC-HF clinical trial on omecamtiv mecarbil in patients with heart failure with reduced ejection fraction (HFrEF) showed it does not affect a person’s exercise capacity. 

The study covered 276 patients in nine countries who were given the drug and then observed after 20 weeks of treatment with omecamtiv mecarbil and standard of care therapy. Using cardiopulmonary exercise testing to measure activity, the researchers recorded an average left ventricular ejection fraction of 27% and an average peak oxygen uptake of 14.7 ml/kg/min at baseline. 

After 20 weeks, there was no change in pVO2 in patients who received omecamtiv mecarbil compared to the placebo group. There were also no beneficial effects in any of the study’s secondary endpoints, including changes in ventilatory efficiency, changes in total workload while exercising and changes in daily physical activity.  

In the same announcement, Cytokinetics shared additional data from its GALACTIC-HF study, which demonstrated a 19% reduction in costs per patient among those who received omecamtiv mecarbil. Of the expense reductions, around 99% were because the drug had helped patients avoid hospitalizations related to heart failure. 

“These findings further our understanding of the potential benefit omecamtiv mecarbil may have in patients at risk for worsening heart failure, as well as the impact it may have on potential cost savings for the healthcare system,” noted Fady I. Malik, MD, Ph.D., the executive vice president of research and development at Cytokinetics, in a press release. 

BridgeBio’s ATTR Stabilization Drug Continues to Prove Safety

Topline data from BridgeBio Pharma’s Phase II open-label study of acoramidis in patients diagnosed with transthyretin amyloidosis (ATTR) showed that the drug had generally remained well-tolerated, without any safety signals of clinical concern. 

Acoramidis, an orally-administered medication designed to stabilize tetrameric transthyretin, is currently being assessed in Phase II and Phase III trials in patients with ATTR. Stabilization is crucial to ATTR patients as it helps preserve the benefits of TTR and address the main cause of the disease. 

BridgeBio’s trial is expected to present topline data for the 30th month by mid-2023. By then, the company said that it is optimistic that it will hit its primary endpoint, composed of all-cause mortality and cardiovascular hospitalizations. 

Esperion Presents “Significant Reduction” in LDL-C

Ann Arbor, Michigan-based Esperion revealed observations from two Phase III trials on the use of Nexletol (bempedoic acid) in different diseases. The first analysis showed that the drug was effective and generally well-tolerated by patients diagnosed with Stage 1 or Stage 3 renal impairment, while the second analysis showed a significant reduction in LDL-C in participant patients, 78% of whom had a history of hypertension. 

Nexletol is an ATP citrate lyase inhibitor that lowers LDL-C. It is the first oral, once-daily, non-statin for LDL-C lowering approved in the U.S. for two decades for patients with HeFH or ASCVD. In Europe, it is sold under the name Nilemdo, with a different label.

Ionis and AstraZeneca’s Cholesterol Drug Hits the Mark in Phase IIb

Ionis Pharmaceuticals and AstraZeneca presented positive results from the Phase IIb ETESIAN trial of ION449 to reduce blood cholesterol levels. The drug is an antisense therapeutic that targets proprotein convertase subtilism/kexin type 9 (PCSK9).

ETESIAN hit its primary endpoint, reducing serum LDL-C levels by up to 79%, with both the 50mg and 90mg doses achieving statistically significant and clinically meaningful decreases in LDL-C levels from baseline of 77% and 79%, respectively, compared to 2% in the placebo group. Those decreases remained until Week 14, or six weeks after the last dose. The drug was generally well-tolerated.

“The positive results of the ETESIAN study, along with the clinical studies to date, reinforces our confidence that ION449 (AZD8233) is a potential new treatment option that may be able to change the current standard of care for patients affected by hypercholesterolemia who have cardiovascular disease,” stated Brett P. Monia, Ph.D., Ionis’ chief executive officer.

The drug is dosed once a month by way of subcutaneous administration. It leverages Ionis’ Ligand-Conjugated Antisense (LICA) technology platform. People with lifelong reduction of LDL-C due to reduced function of PCSK9 have a substantially decreased risk of cardiovascular diseases. Therefore, inhibiting PCSK9 substantially decreases LDL-C.

Pfizer’s Vupanorsen Decreases Non-HDL by Up to 28%

Dr. Brian Bergmark, MD, a cardiologist at Brigham and Women’s Hospital in Boston presented data from the TRANSLATE-TIMI 7088 trial of Pfizer’s vupanorsen. The drug showed modest reductions in non-HDL cholesterol in adults were already receiving statins. It decreased non-HDL by up to 28%, but lowered triglyceride levels by up to 57%, and ANGPTL3 by up to 95%. Its effects on LDL and apolipoprotein B (apoB) levels were modest.

Vupanorsen lowers non-HDL by decrease production of ANGPTL3, a protein that inhibits metabolic enzymes related to triglyceride and cholesterol

“Regardless of the future of this compound, we did find out some information that may be quite relevant for future studies,” Bergmark said. “There are numerous other compounds targeting this pathway or adjacent metabolic pathways through similar mechanisms, and it will be interesting to see how this plays out for other agents.”

Sanofi and Regeneron’s Praluent with Statins Improves Coronary Plaque Regression

Data from the PACMAN-AMI trial demonstrated that adding Sanofi and Regeneron’s Praluent (alirocumab) to high-intensity statin therapy improves coronary plaque regression and stabilization when initiated early after an acute myocardial infarction (MI). The combination offered better decreases in percent atheroma volume and lipid burden in addition to a greater increase in minimal fibrous cap thickness. The data was reported by Dr. Lorenz Raber, MD, Ph.D., with Bern University Hospital in Switzerland.

Raber said the data, which was published simultaneously online in JAMA, “provide the mechanistic rationale in favor of an early initiation of very intensive LDL-lowering in acute MI patients.”

Early Clinical Data on Small interfering RNA Therapy for Cholesterol

Dr. Steven E. Nissen, MD, a cardiologist at the Cleveland Clinic, presented Phase I APOLLO data of SLN360, a small interfering RNA (siRNA) on cholesterol levels. SLN360 is Silence Therapeutics’ wholly owned siRNA experimental therapeutic. siRNA therapies are designed to temporarily block a specific gene’s encoding that would otherwise cause an unwanted biological effect. SLN360 is designed to silence LPA, a gene that codes for a specific protein only found in lipoprotein(a)[Lp(a)]. This decreases Lp(a) levels, which they believe will decrease the risk of heart diseases, heart attacks and strokes.

The investigators wrote, “Plasma LP(a) levels are genetically determined and are not influenced by lifestyle interventions, such as diet and exercise, that reduce low-density lipoprotein cholesterol and triglycerides or increase high-density lipoprotein cholesterol. In the absence of an effective Lp(a)-lowering drug therapy, this risk factor has traditionally been considered essentially untreatable.”