User login
Finerenone, the first nonsteroidal mineralocorticoid receptor antagonist to complete a phase 3 trial, showed cardiovascular benefits in patients with type 2 diabetes and chronic kidney disease, regardless of whether they entered the study with a history of cardiovascular disease, in follow-up analyses of the FIDELIO-DKD trial, which included 5,674 patients.
“Finerenone demonstrated benefits for primary and secondary cardiovascular disease protection,” said Gerasimos Filippatos, MD, at the American Heart Association scientific sessions. Finerenone treatment cut the rate of cardiovascular death, nonfatal MI or stroke, or heart failure hospitalization, when compared with placebo, by a relative 15% among patients with a history of cardiovascular disease (CVD), and by a relative 14% in patients without this history, differences that met a statistical test for consistency. But the absolute, drug-associated increments in benefit over placebo differed between the two CVD subgroups because of a sharp underlying difference in event rates.
In contrast, the analyses reported by Dr. Filippatos and associates from the FIDELIO-DKD study showed significant heterogeneity based on the presence or absence of CVD for the study’s primary endpoint, a composite renal metric that tallied the combined rate of death from renal causes, renal failure, or a sustained drop in estimated glomerular filtration rate of at least 40%. Researchers enrolled patients into FIDELIO-DKD based on having type 2 diabetes (T2D) and chronic kidney disease (CKD). The prevalence of a history of CVD was 46%.
Among patients with a history of CVD, the composite adverse CVD outcome occurred at a rate of 8.5/100 patient-years in patients on placebo and in 7.18/100 patients years among those on finerenone during a median of 2.6 years of follow-up, a 1.32/100–patient-year absolute between-group difference. Among patients in a primary prevention setting, incident CVD event rates during follow-up were roughly half that in the secondary prevention patients. The upshot was that, in the placebo group, the rate was 3.92/100 patient- years, and in those on finerenone was 3.43/100 patient-years, a 0.49/100–patient-year absolute difference.
CVD history produced heterogeneity for the primary endpoint
In the analysis that focused on the study’s primary, renal endpoint, among patients identified as having CVD at study entry, the outcome occurred at a rate of 9.06/100 patient-years in the placebo subgroup and at a rate of 6.6/100 patient years in those who received finerenone, a significant 30% relative risk reduction and an absolute between-group difference of 2.46/100 patient-years.
In contrast, among patients without a CVD history, the composite renal endpoint occurred at a rate of 9.1/100 patient-years in the placebo patients and 8.42/100 patient-years in those on finerenone, a 6% relative risk reduction that was not significant, and a 0.68/100–patient-year absolute difference. This disparity in the primary event rate between the two treatment arms reached statistical significance (P = .016), the investigators reported in the published version of the report in Circulation that simultaneously appeared online.
“The totality of evidence suggests that finerenone could be used in patients with T2D with or without a history of CVD,” explained Dr. Filippatos in an interview. “The P-interaction for the composite kidney outcome is significant, but it is not corrected for multiple testing; therefore, it might be a false-chance finding and must be interpreted cautiously.
Furthermore, in another prespecified kidney composite outcome the results were consistent in patients with and without a history of CVD. In sum, all the FIDELIO-DKD analyses so far are “suggestive of a beneficial effect in patients without a history of CVD.”
Despite these patients receiving guideline directed therapies, “there remains a high unmet medical need in patients with T2D and CKD,” added Dr. Filippatos, professor of cardiology at the University of Athens. “We use multiple treatments for patients with heart failure, and we should use the same mindset for treating patients with T2D and CKD. The costs of dialysis and kidney transplant are very high, so it is important to consider options that slow progression of CKD in these patients.”
In FIDELIO-DKD, virtually all patients were on background therapy with a renin-angiotensin-system (RAS) inhibitor, so the trial’s results suggest that treatment should at least involve dual therapy with finerenone and a RAS inhibitor. Fewer than 5% were on background therapy with a sodium-glucose cotransporter 2 (SGLT2) inhibitor, a drug class recently established as another key agent for treating CKD in patients with T2D, setting up the prospect for triple therapy, although this approach has not yet undergone prospective testing.
Combining RAS inhibition, finerenone, and an SGLT2 inhibitor is “potentially a marriage made in diabetes heaven,” commented Deepak L. Bhatt, MD, a professor of medicine at Harvard Medical School, Boston, who has not participated in finerenone studies.
Finerenone looks better for safety
Regardless of subgroup analyses based on history of CVD, the findings from all patients enrolled in FIDELIO-DKD were positive for the both the primary renal outcome and key secondary outcome of composite CVD events. In the total randomized cohort, treatment with finerenone on top of optimized treatment with an ACE inhibitor or angiotensin receptor blocker (RAS inhibition) led to a significant 18% relative risk reduction, compared with placebo, for the primary renal endpoint, and a significant 14% relative drop in the key secondary CVD outcome. Those results were published in October in the New England Journal of Medicine.
For treating patients with T2D and CKD ,finerenone overall “looks like a major advance,” Dr. Bhatt said in an interview.
In addition to the positive efficacy results, several experts also focused on what they saw as superior safety of finerenone in the trial, compared with the historical safety of the steroidal mineralocorticoid receptor antagonists (MRAs) now in use: spironolactone and eplerenone.
“I’m a big believer in spironolactone, but it has issues with side effects, and eplerenone never seemed to catch on,” said Dr. Bhatt, who is also executive director of interventional cardiovascular programs at Brigham and Women’s Hospital in Boston.
“A lot of physicians like these MRAs, but acknowledge that side effects have kept these drugs from being used to the extent they should.” The existing MRAs, especially spironolactone, have become a key drug class for treating heart failure with reduced ejection fraction (and, some claim, for also treating heart failure with preserved ejection fraction), as well as treatment-resistant hypertension and primary aldosteronism. By design, FIDELIO-DKD did not enroll patients with heart failure because treatment with an MRA is indicated for those with heart failure with reduced ejection fraction.
The spironolactone adverse effect that generates the greatest concern is hyperkalemia. During his discussion of FIDELIO-DKD as designated discussant, Christoph Wanner, MD, noted a recent study in which the incidence of hyperkalemia severe enough to cause study discontinuation was 23% among patients treated with spironolactone for heart failure, which contrasts with the 2.3% rate in FIDELIO-DKD among finerenone recipients. This hyperkalemia incidence from finerenone also improved on the historical performance of other drugs, like aliskiren (Tekturna), said Dr. Wanner, professor and head of nephrology at the University of Würzburg (Germany).
The FIDELIO-DKD results place finerenone alongside the RAS- and SGLT2-inhibitor drug classes as appropriate treatments for most patients with T2D and CKD. “We have entered a new era of effective treatment for diabetic kidney disease,” Dr. Wanner declared.
“The overall safety profile of finerenone looked better, including hyperkalemia,” said Dr. Bhatt. “Hyperkalemia with spironolactone is not necessarily as bad as the perception. With careful monitoring of spironolactone, the hyperkalemia is manageable. But the perception is that it’s bad, and along with gynecomastia it’s a real killer.”
While some dismiss gynecomastia as a major concern (for men) with spironolactone treatment, “if medical students learn one thing about spironolactone, it’s that it can cause gynecomastia,” adding to the negative image that the approved MRAs carry, Dr. Bhatt said.
“The hyperkalemia was manageable. This is very important because of past problems with potassium when using spironolactone,” Dr. Filippatos said. Finerenone also looks “more cardiorenal protective” than the steroidal MRAs, exerting renal benefits in FIDELIO-DKD never previously described for a steroidal MRA.
Some of the uncertainty about the efficacy of finerenone in patients with a history of cardiovascular disease will lift when results are available in about another year from the FIGARO-DKD pivotal trial of finerenone, which enrolled more than 7,000 patients with T2D and CKD (entry criteria very similar to FIDELIO-CKD). A big difference is that FIGARO-DKD has a composite CVD event metric as its primary endpoint, and includes hospitalization for heart failure as one facet of the composite.
FIDELIO-DKD was sponsored by Bayer. Dr. Filippatos has been a lecturer on behalf of, served as a researcher for, or both for Bayer and also for Amgen, Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor. Dr. Bhatt has received research funding from Bayer and also from several other companies, and he also is an adviser to several companies. Dr. Wanner has received honoraria from Bayer, and also from AstraZeneca, Boehringer Ingelheim, FMC, Gilead, GlaxoSmithKline, Lilly, and Merck.
Finerenone, the first nonsteroidal mineralocorticoid receptor antagonist to complete a phase 3 trial, showed cardiovascular benefits in patients with type 2 diabetes and chronic kidney disease, regardless of whether they entered the study with a history of cardiovascular disease, in follow-up analyses of the FIDELIO-DKD trial, which included 5,674 patients.
“Finerenone demonstrated benefits for primary and secondary cardiovascular disease protection,” said Gerasimos Filippatos, MD, at the American Heart Association scientific sessions. Finerenone treatment cut the rate of cardiovascular death, nonfatal MI or stroke, or heart failure hospitalization, when compared with placebo, by a relative 15% among patients with a history of cardiovascular disease (CVD), and by a relative 14% in patients without this history, differences that met a statistical test for consistency. But the absolute, drug-associated increments in benefit over placebo differed between the two CVD subgroups because of a sharp underlying difference in event rates.
In contrast, the analyses reported by Dr. Filippatos and associates from the FIDELIO-DKD study showed significant heterogeneity based on the presence or absence of CVD for the study’s primary endpoint, a composite renal metric that tallied the combined rate of death from renal causes, renal failure, or a sustained drop in estimated glomerular filtration rate of at least 40%. Researchers enrolled patients into FIDELIO-DKD based on having type 2 diabetes (T2D) and chronic kidney disease (CKD). The prevalence of a history of CVD was 46%.
Among patients with a history of CVD, the composite adverse CVD outcome occurred at a rate of 8.5/100 patient-years in patients on placebo and in 7.18/100 patients years among those on finerenone during a median of 2.6 years of follow-up, a 1.32/100–patient-year absolute between-group difference. Among patients in a primary prevention setting, incident CVD event rates during follow-up were roughly half that in the secondary prevention patients. The upshot was that, in the placebo group, the rate was 3.92/100 patient- years, and in those on finerenone was 3.43/100 patient-years, a 0.49/100–patient-year absolute difference.
CVD history produced heterogeneity for the primary endpoint
In the analysis that focused on the study’s primary, renal endpoint, among patients identified as having CVD at study entry, the outcome occurred at a rate of 9.06/100 patient-years in the placebo subgroup and at a rate of 6.6/100 patient years in those who received finerenone, a significant 30% relative risk reduction and an absolute between-group difference of 2.46/100 patient-years.
In contrast, among patients without a CVD history, the composite renal endpoint occurred at a rate of 9.1/100 patient-years in the placebo patients and 8.42/100 patient-years in those on finerenone, a 6% relative risk reduction that was not significant, and a 0.68/100–patient-year absolute difference. This disparity in the primary event rate between the two treatment arms reached statistical significance (P = .016), the investigators reported in the published version of the report in Circulation that simultaneously appeared online.
“The totality of evidence suggests that finerenone could be used in patients with T2D with or without a history of CVD,” explained Dr. Filippatos in an interview. “The P-interaction for the composite kidney outcome is significant, but it is not corrected for multiple testing; therefore, it might be a false-chance finding and must be interpreted cautiously.
Furthermore, in another prespecified kidney composite outcome the results were consistent in patients with and without a history of CVD. In sum, all the FIDELIO-DKD analyses so far are “suggestive of a beneficial effect in patients without a history of CVD.”
Despite these patients receiving guideline directed therapies, “there remains a high unmet medical need in patients with T2D and CKD,” added Dr. Filippatos, professor of cardiology at the University of Athens. “We use multiple treatments for patients with heart failure, and we should use the same mindset for treating patients with T2D and CKD. The costs of dialysis and kidney transplant are very high, so it is important to consider options that slow progression of CKD in these patients.”
In FIDELIO-DKD, virtually all patients were on background therapy with a renin-angiotensin-system (RAS) inhibitor, so the trial’s results suggest that treatment should at least involve dual therapy with finerenone and a RAS inhibitor. Fewer than 5% were on background therapy with a sodium-glucose cotransporter 2 (SGLT2) inhibitor, a drug class recently established as another key agent for treating CKD in patients with T2D, setting up the prospect for triple therapy, although this approach has not yet undergone prospective testing.
Combining RAS inhibition, finerenone, and an SGLT2 inhibitor is “potentially a marriage made in diabetes heaven,” commented Deepak L. Bhatt, MD, a professor of medicine at Harvard Medical School, Boston, who has not participated in finerenone studies.
Finerenone looks better for safety
Regardless of subgroup analyses based on history of CVD, the findings from all patients enrolled in FIDELIO-DKD were positive for the both the primary renal outcome and key secondary outcome of composite CVD events. In the total randomized cohort, treatment with finerenone on top of optimized treatment with an ACE inhibitor or angiotensin receptor blocker (RAS inhibition) led to a significant 18% relative risk reduction, compared with placebo, for the primary renal endpoint, and a significant 14% relative drop in the key secondary CVD outcome. Those results were published in October in the New England Journal of Medicine.
For treating patients with T2D and CKD ,finerenone overall “looks like a major advance,” Dr. Bhatt said in an interview.
In addition to the positive efficacy results, several experts also focused on what they saw as superior safety of finerenone in the trial, compared with the historical safety of the steroidal mineralocorticoid receptor antagonists (MRAs) now in use: spironolactone and eplerenone.
“I’m a big believer in spironolactone, but it has issues with side effects, and eplerenone never seemed to catch on,” said Dr. Bhatt, who is also executive director of interventional cardiovascular programs at Brigham and Women’s Hospital in Boston.
“A lot of physicians like these MRAs, but acknowledge that side effects have kept these drugs from being used to the extent they should.” The existing MRAs, especially spironolactone, have become a key drug class for treating heart failure with reduced ejection fraction (and, some claim, for also treating heart failure with preserved ejection fraction), as well as treatment-resistant hypertension and primary aldosteronism. By design, FIDELIO-DKD did not enroll patients with heart failure because treatment with an MRA is indicated for those with heart failure with reduced ejection fraction.
The spironolactone adverse effect that generates the greatest concern is hyperkalemia. During his discussion of FIDELIO-DKD as designated discussant, Christoph Wanner, MD, noted a recent study in which the incidence of hyperkalemia severe enough to cause study discontinuation was 23% among patients treated with spironolactone for heart failure, which contrasts with the 2.3% rate in FIDELIO-DKD among finerenone recipients. This hyperkalemia incidence from finerenone also improved on the historical performance of other drugs, like aliskiren (Tekturna), said Dr. Wanner, professor and head of nephrology at the University of Würzburg (Germany).
The FIDELIO-DKD results place finerenone alongside the RAS- and SGLT2-inhibitor drug classes as appropriate treatments for most patients with T2D and CKD. “We have entered a new era of effective treatment for diabetic kidney disease,” Dr. Wanner declared.
“The overall safety profile of finerenone looked better, including hyperkalemia,” said Dr. Bhatt. “Hyperkalemia with spironolactone is not necessarily as bad as the perception. With careful monitoring of spironolactone, the hyperkalemia is manageable. But the perception is that it’s bad, and along with gynecomastia it’s a real killer.”
While some dismiss gynecomastia as a major concern (for men) with spironolactone treatment, “if medical students learn one thing about spironolactone, it’s that it can cause gynecomastia,” adding to the negative image that the approved MRAs carry, Dr. Bhatt said.
“The hyperkalemia was manageable. This is very important because of past problems with potassium when using spironolactone,” Dr. Filippatos said. Finerenone also looks “more cardiorenal protective” than the steroidal MRAs, exerting renal benefits in FIDELIO-DKD never previously described for a steroidal MRA.
Some of the uncertainty about the efficacy of finerenone in patients with a history of cardiovascular disease will lift when results are available in about another year from the FIGARO-DKD pivotal trial of finerenone, which enrolled more than 7,000 patients with T2D and CKD (entry criteria very similar to FIDELIO-CKD). A big difference is that FIGARO-DKD has a composite CVD event metric as its primary endpoint, and includes hospitalization for heart failure as one facet of the composite.
FIDELIO-DKD was sponsored by Bayer. Dr. Filippatos has been a lecturer on behalf of, served as a researcher for, or both for Bayer and also for Amgen, Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor. Dr. Bhatt has received research funding from Bayer and also from several other companies, and he also is an adviser to several companies. Dr. Wanner has received honoraria from Bayer, and also from AstraZeneca, Boehringer Ingelheim, FMC, Gilead, GlaxoSmithKline, Lilly, and Merck.
Finerenone, the first nonsteroidal mineralocorticoid receptor antagonist to complete a phase 3 trial, showed cardiovascular benefits in patients with type 2 diabetes and chronic kidney disease, regardless of whether they entered the study with a history of cardiovascular disease, in follow-up analyses of the FIDELIO-DKD trial, which included 5,674 patients.
“Finerenone demonstrated benefits for primary and secondary cardiovascular disease protection,” said Gerasimos Filippatos, MD, at the American Heart Association scientific sessions. Finerenone treatment cut the rate of cardiovascular death, nonfatal MI or stroke, or heart failure hospitalization, when compared with placebo, by a relative 15% among patients with a history of cardiovascular disease (CVD), and by a relative 14% in patients without this history, differences that met a statistical test for consistency. But the absolute, drug-associated increments in benefit over placebo differed between the two CVD subgroups because of a sharp underlying difference in event rates.
In contrast, the analyses reported by Dr. Filippatos and associates from the FIDELIO-DKD study showed significant heterogeneity based on the presence or absence of CVD for the study’s primary endpoint, a composite renal metric that tallied the combined rate of death from renal causes, renal failure, or a sustained drop in estimated glomerular filtration rate of at least 40%. Researchers enrolled patients into FIDELIO-DKD based on having type 2 diabetes (T2D) and chronic kidney disease (CKD). The prevalence of a history of CVD was 46%.
Among patients with a history of CVD, the composite adverse CVD outcome occurred at a rate of 8.5/100 patient-years in patients on placebo and in 7.18/100 patients years among those on finerenone during a median of 2.6 years of follow-up, a 1.32/100–patient-year absolute between-group difference. Among patients in a primary prevention setting, incident CVD event rates during follow-up were roughly half that in the secondary prevention patients. The upshot was that, in the placebo group, the rate was 3.92/100 patient- years, and in those on finerenone was 3.43/100 patient-years, a 0.49/100–patient-year absolute difference.
CVD history produced heterogeneity for the primary endpoint
In the analysis that focused on the study’s primary, renal endpoint, among patients identified as having CVD at study entry, the outcome occurred at a rate of 9.06/100 patient-years in the placebo subgroup and at a rate of 6.6/100 patient years in those who received finerenone, a significant 30% relative risk reduction and an absolute between-group difference of 2.46/100 patient-years.
In contrast, among patients without a CVD history, the composite renal endpoint occurred at a rate of 9.1/100 patient-years in the placebo patients and 8.42/100 patient-years in those on finerenone, a 6% relative risk reduction that was not significant, and a 0.68/100–patient-year absolute difference. This disparity in the primary event rate between the two treatment arms reached statistical significance (P = .016), the investigators reported in the published version of the report in Circulation that simultaneously appeared online.
“The totality of evidence suggests that finerenone could be used in patients with T2D with or without a history of CVD,” explained Dr. Filippatos in an interview. “The P-interaction for the composite kidney outcome is significant, but it is not corrected for multiple testing; therefore, it might be a false-chance finding and must be interpreted cautiously.
Furthermore, in another prespecified kidney composite outcome the results were consistent in patients with and without a history of CVD. In sum, all the FIDELIO-DKD analyses so far are “suggestive of a beneficial effect in patients without a history of CVD.”
Despite these patients receiving guideline directed therapies, “there remains a high unmet medical need in patients with T2D and CKD,” added Dr. Filippatos, professor of cardiology at the University of Athens. “We use multiple treatments for patients with heart failure, and we should use the same mindset for treating patients with T2D and CKD. The costs of dialysis and kidney transplant are very high, so it is important to consider options that slow progression of CKD in these patients.”
In FIDELIO-DKD, virtually all patients were on background therapy with a renin-angiotensin-system (RAS) inhibitor, so the trial’s results suggest that treatment should at least involve dual therapy with finerenone and a RAS inhibitor. Fewer than 5% were on background therapy with a sodium-glucose cotransporter 2 (SGLT2) inhibitor, a drug class recently established as another key agent for treating CKD in patients with T2D, setting up the prospect for triple therapy, although this approach has not yet undergone prospective testing.
Combining RAS inhibition, finerenone, and an SGLT2 inhibitor is “potentially a marriage made in diabetes heaven,” commented Deepak L. Bhatt, MD, a professor of medicine at Harvard Medical School, Boston, who has not participated in finerenone studies.
Finerenone looks better for safety
Regardless of subgroup analyses based on history of CVD, the findings from all patients enrolled in FIDELIO-DKD were positive for the both the primary renal outcome and key secondary outcome of composite CVD events. In the total randomized cohort, treatment with finerenone on top of optimized treatment with an ACE inhibitor or angiotensin receptor blocker (RAS inhibition) led to a significant 18% relative risk reduction, compared with placebo, for the primary renal endpoint, and a significant 14% relative drop in the key secondary CVD outcome. Those results were published in October in the New England Journal of Medicine.
For treating patients with T2D and CKD ,finerenone overall “looks like a major advance,” Dr. Bhatt said in an interview.
In addition to the positive efficacy results, several experts also focused on what they saw as superior safety of finerenone in the trial, compared with the historical safety of the steroidal mineralocorticoid receptor antagonists (MRAs) now in use: spironolactone and eplerenone.
“I’m a big believer in spironolactone, but it has issues with side effects, and eplerenone never seemed to catch on,” said Dr. Bhatt, who is also executive director of interventional cardiovascular programs at Brigham and Women’s Hospital in Boston.
“A lot of physicians like these MRAs, but acknowledge that side effects have kept these drugs from being used to the extent they should.” The existing MRAs, especially spironolactone, have become a key drug class for treating heart failure with reduced ejection fraction (and, some claim, for also treating heart failure with preserved ejection fraction), as well as treatment-resistant hypertension and primary aldosteronism. By design, FIDELIO-DKD did not enroll patients with heart failure because treatment with an MRA is indicated for those with heart failure with reduced ejection fraction.
The spironolactone adverse effect that generates the greatest concern is hyperkalemia. During his discussion of FIDELIO-DKD as designated discussant, Christoph Wanner, MD, noted a recent study in which the incidence of hyperkalemia severe enough to cause study discontinuation was 23% among patients treated with spironolactone for heart failure, which contrasts with the 2.3% rate in FIDELIO-DKD among finerenone recipients. This hyperkalemia incidence from finerenone also improved on the historical performance of other drugs, like aliskiren (Tekturna), said Dr. Wanner, professor and head of nephrology at the University of Würzburg (Germany).
The FIDELIO-DKD results place finerenone alongside the RAS- and SGLT2-inhibitor drug classes as appropriate treatments for most patients with T2D and CKD. “We have entered a new era of effective treatment for diabetic kidney disease,” Dr. Wanner declared.
“The overall safety profile of finerenone looked better, including hyperkalemia,” said Dr. Bhatt. “Hyperkalemia with spironolactone is not necessarily as bad as the perception. With careful monitoring of spironolactone, the hyperkalemia is manageable. But the perception is that it’s bad, and along with gynecomastia it’s a real killer.”
While some dismiss gynecomastia as a major concern (for men) with spironolactone treatment, “if medical students learn one thing about spironolactone, it’s that it can cause gynecomastia,” adding to the negative image that the approved MRAs carry, Dr. Bhatt said.
“The hyperkalemia was manageable. This is very important because of past problems with potassium when using spironolactone,” Dr. Filippatos said. Finerenone also looks “more cardiorenal protective” than the steroidal MRAs, exerting renal benefits in FIDELIO-DKD never previously described for a steroidal MRA.
Some of the uncertainty about the efficacy of finerenone in patients with a history of cardiovascular disease will lift when results are available in about another year from the FIGARO-DKD pivotal trial of finerenone, which enrolled more than 7,000 patients with T2D and CKD (entry criteria very similar to FIDELIO-CKD). A big difference is that FIGARO-DKD has a composite CVD event metric as its primary endpoint, and includes hospitalization for heart failure as one facet of the composite.
FIDELIO-DKD was sponsored by Bayer. Dr. Filippatos has been a lecturer on behalf of, served as a researcher for, or both for Bayer and also for Amgen, Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor. Dr. Bhatt has received research funding from Bayer and also from several other companies, and he also is an adviser to several companies. Dr. Wanner has received honoraria from Bayer, and also from AstraZeneca, Boehringer Ingelheim, FMC, Gilead, GlaxoSmithKline, Lilly, and Merck.
FROM AHA 2020
