A pair of trials involving sotagliflozin—a unique diabetes drug with a rocky history at FDA—suggest it offers benefits for patients who have heart failure with preserved ejection fraction (HFpEF), marking the first time investigators have shown this in a prospective trial.

, presented this evening at the American Heart Association Scientific Sessions, also found that the dual inhibitor resulted in fewer cardiovascular (CV) events and can offer glycemic control even for patients with lower levels of renal function. This latter finding offers some irony, since the 

 from smaller trials in chronic kidney disease (CKD) led to the breakup between drug sponsor 

According to the lead investigator, Deepak L. Bhatt, MD, of Harvard Medical School, the findings suggest that sotagliflozin could be an option for patients with significant comorbidities; if given to those hospitalized for heart failure, sotagliflozin could keep them from being readmitted—a priority in managed care. The findings were simultaneously published in the 

The results come more than a year after Sanofi 

 with Lexicon following disagreements over how to interpret early findings from the SOTA-CKD3 and SOTA-CKD4 studies, which evaluated its effectiveness in patients with moderate and advanced renal decline. FDA had also twice rejected the drug’s 

 as an add-on to insulin in type 1 diabetes (T1D).

Loss of funding during the COVID-19 pandemic forced an early end to the pair of phase 3 trials released today. While cautious about interpreting the HFpEF signal, Bhatt said he believes it should indicate good news from other trials studying sodium glucose co-transporter 2 (SGLT2) inhibitors in this hard-to-treat condition. Right now, there are no approved treatments for HFpEF, although 

 a new drug application from Novartis to evaluate sacubitril/valsartan (Entresto) for this use.

The road from here is complicated for sotagliflozin. When the trials had to end early, 

Bhatt and co-authors had to revamp end points and skip some planned analyses, which they acknowledge as limitations. But the data are strong enough, Bhatt said, to warrant another look from FDA.

There are distinct groups of patients who would benefit from the dual inhibitor mechanism of sotagliflozin, he said. “One particular niche could be patients with severe kidney disease.”

Sotagliflozin is a dual inhibitor, meaning it targets proteins in both the gut and the renal system—sodium glucose co-transporters 1 and 2—that affect how the body retains or processes blood glucose. SGLT2 inhibitors, which reached the market in 2013, were designed to manage type 2 diabetes (T2D) by targeting the SGLT2 protein in the kidney, blocking its ability to retain up to 90% of filtered glucose. CV outcomes trials required by FDA revealed unexpected benefits in heart failure and preservation of kidney function, setting off a race for more studies to gain approvals in these conditions.

Unlike current rivals in the SGLT2 class, sotagliflozin also targets the SGLT1 protein, which affects the absorption of glucose in the gastrointestinal tract. The drug was approved for T2D (marketed as Zynquista) but also sought approval to stabilize the glycemic variability that affects the 1.25 million US patients with T1D. This use is approved in Europe. But FDA balked, citing concerns about diabetic ketoacidosis.

This trial randomly assigned 1222 patients with T2D who were recently hospitalized for worsening heart failure to receive either sotagliflozin or placebo. The primary end point was the total number of deaths from CV causes and hospitalizations and urgent visits for heart failure, including first and subsequent events. Patients were followed for a median of 9.0 months, with 48.8% getting their first dose of the study drug or placebo before discharge and 51.2% receiving it within 2 days. Results showed:

The rate of primary end point events in the trial (events per 100 patient years) was 51.0 in the sotagliflozin group and 76.3 in the placebo group for a hazard ratio (HR) of 0.67; 95% CI, 0.52-0.85, 

The death rate from any cause was 13.5 in the sotagliflozin group and 16.3 in the placebo group (HR, 0.82; 95% CI, 0.59-1.14)

More patients with sotagliflozin had diarrhea (6.1% vs 3.4%) and more had severe hypoglycemia (1.5% vs 0.3%), but the percentages of hypotension were similar (6.0% sotagliflozin vs 4.6% placebo).

The percentage of patients with acute kidney injury was similar (4.1% for sotagliflozin vs 4.4% for placebo).

This trial evaluated sotagliflozin’s ability to prevent CV events in patients with diabetes and CKD with or without albuminuria. This study randomized 10,584 to sotagliflozin or placebo, with a revised primary end point of the total number of deaths from CV disease, total hospitalizations for heart failure, and urgent visits for heart failure. Results include:

The rate of primary end point events (events per 100 patient years) was 5.6 for sotagliflozin and 7.5 for placebo, for an HR of 0.74 (95% CI, 0.63-0.88), 

The rate of deaths from CV causes per 100 patient-years was 2.2 with sotagliflozin and 2.4 with placebo (HR, 0.90; 95% CI, 0.73 to 1.12; 

Two original coprimary end points were reported: first occurrence of death from CV causes, nonfatal myocardial infarction, or nonfatal stroke, with an HR of 0.84 (95% CI, 0.72 to 0.99); and first occurrence of death from CV causes or hospitalization for heart failure, with an HR of 0.77 (95% CI, 0.66 to 0.91).

The total number of deaths from CV causes, hospitalizations for HF, nonfatal myocardial infarctions, and nonfatal strokes was 7.6 for sotagliflozin and 10.4 for placebo, for an HR of 0.72 (0.72 (0.63–0.83).

Bhatt showed data indicating the reduction in glycated hemoglobin (A1C) was twice as great as placebo across both moderate (eGFR ≥30 ml/min/1.73 m2) and severe eGFR <30 ml/min/1.73 m2) renal decline.

The first occurrence of a sustained decrease of ≥50% in the eGFR from baseline for ≥30 days, long-term dialysis, renal transplantation, or sustained eGFR of <15 ml/min/1.73 m2 for ≥30 days was 0.5 events per 100 patient years in sotagliflozin and 0.7 events for placebo, for an HR of 0.71 (0.46–1.08).

Bhatt said other evidence has suggested that SGLT2 inhibition could offer benefits in HFpEF, but until now investigators have not found a signal in a prospective trial. During Monday's evening session, he presented pooled data from the SOLOIST-WHF and SCORED trials, and found that the HR for 1758 patients with HFrEF was 0.78 (95% CI, 0.63–0.96, 

 = .02), and the HR for 739 patients with HFpEF was 0.63 (95% CI, 0.45-0.89, P= .009).

“For the first time we've actually demonstrated prospectively that an SGLT2 inhibitor with SGLT1 inhibition capability is something that is useful for heart failure with preserved ejection fraction,” he said, noting that there are 2 ongoing trials, DELIVER for dapagliflozin and EMPEROR-Preserved for empagliflozin, that are examining this question for SGLT2 inhibitors.

“I would predict based on the results of SOLOIST, and the combined SOLOIST/SCORED [results], for that those trials will also be positive,” Bhatt said in response to a question from 

Dapagliflozin received approval earlier this year to treat patients with heart failure with reduced ejection fraction (HFrEF), and results presented in August show empagliflozin (Jardiance) is effective in HFrEF.

1. Bhatt DL, Szarek M, Steg PG, et al. for the SOLOIST-WHF Trial Investigators. Sotagliflozin in patients with diabetes and recent worsening heart failure for the SOLOIST-WHF Trial. 

. Published online November 16, 2020. doi: 10.1056/NEJMoa2030183

2. Bhatt DL, Szarek M, Pitt B, et al., for the SCORED Trial Investigators. Sotagliflozin in patients with diabetes and chronic kidney disease. 

. Published online November 16, 2020. doi: 10.1056/NEJMoa2030186

Articles

American Heart Association Scientific Sessions

After recent setbacks, the beleaguered drug reduced cardiovascular events and may be a choice for patients with severe chronic kidney disease.

Sotagliflozin Findings Suggest Benefit for Hard-to-Treat HF Population

The debate over whether medications derived from fish oil can prevent cardiac events took another turn today, as a new study from the Cleveland Clinic found that a treatment combining 2 common omega-3 fatty acids did not reduce the risk of cardiac events.

The findings, along with those from a study testing fish oil in seniors, directly challenge results of the REDUCE-IT trial, which found that icosapent ethyl reduced initial cardiac events by 25% and all events by 30%. In December, 

, sold by Amarin as Vascepa, as an add-on therapy to reduce cardiovascular risk. The medication was first approved to treat high triglycerides.

Results presented today at the American Heart Association Scientific Sessions involved the STRENGTH trial, which studied omega-3 carboxylic acid in high-risk patients, and the ONEMI trial, which studied the effects of omega-3 fatty acids in recent heart attack survivors over age 70.

 that said omega-3 fish oil supplements prescribed by clinician may prevent death from heart disease in those who had recently experienced a heart attack, or may prevent death or hospitalization for those with heart heart failure. But the advisory stopped short of recommending the supplements to prevent heart disease in the general population.

Treatments used in REDUCE-IT and STRENGTH have important differences, and so do the placebo tablets used in each trial. Icosapent ethyl contains only eicosapentaenoic acid (EPA), whereas the STRENGTH trial used a therapy containing both EPA and docosahexaenoic acid (DHA). Investigators for REDUCE-IT have pointed out repeatedly that the 4 g daily dose used in that study is a highly purified form of EPA only, and 

 argued that DHA may thwart the effects of EPA.

Since the first results were published, REDUCE-IT investigators have produced follow-up studies showing benefits from icosapent ethyl among specific groups of patients, such as those with 

. Earlier in this year’s AHA meeting, Amarin highlighted post-hoc results showing 

But when REDUCE-IT first appeared, some questioned whether the mineral oil placebo used in the study produced cardiac effects—and thus, made it appear that icosapent ethyl was working wonders.

Today, the lead author of STRENGTH, A. Michael Lincoff, MD, professor of medicine and vice chairman for research, Cardiovascular Medicine, Cleveland Clinic, said a corn oil placebo was selected precisely because it would have a neutral effect, unlike mineral oil, which would create a “negative control.”

The STRENGTH trial, which enrolled more than 13,000 patients in 22 countries starting in 2014, was stopped in January 2020 when results showed it was unlikely to show any benefit for carboxylic acid. It was funded by AstraZeneca.

Regarding the use of fish oil-derived medication more broadly, Lincoff said in a statement, “We believe the questions surrounding the benefit versus risk of fish oil will remain unanswered unless another trial using a neutral placebo such as corn oil is able to definitively show cardiovascular benefits for an omega-3 fatty acid medication.”

Lincoff said the lack of benefit for carboxylic acid occurred even though there was a 269% increase in plasma EPA levels. Unlike the mineral oil used in the REDUCE-IT trial, he said, corn oil did not elevate low-density lipoprotein cholesterol or 2 key biomarkers, ApoB or high-sensitivity C-reactive protein, “suggesting that it was a truly neutral comparator.”

A similar result was seen ONEMI. “The fact that no indication of any impact from the omega-3 fatty acids were found in this group, along with the results of other recent neutral trials, suggests that omega-3 supplements are ineffective for cardiovascular prevention,” said 

Are A. Kalstad, MD, of the Center for Clinical Research at Oslo University Hospital in Oslo, Norway, a 

From his Twitter account, Deepak L. Bhatt, MD, the lead investigator for REDUCE-IT and a professor at Harvard Medical School, directed followers to a recent supplement on the trial that featured an article on the

"There was no consistent evidence that mineral oil in the amounts used in the REDUCE-IT or Effect of Vascepa on Progression of Coronary Atherosclerosis in Patients With Elevated Triglycerides on Statin Therapy (EVAPORATE) trials affects absorption of essential nutrients or drugs, including statins," the authors wrote in the 

published by the European Society of Cardiology.

"These results were then considered alongside publicly available data from REDUCE-IT. Based on available evidence, mineral oil does not appear to impact medication absorption or efficacy, or related clinical outcomes, and, therefore, does not meaningfully affect study conclusions when used as a placebo at the quantities used in clinical trials."

, Bhatt was asked if the STRENGTH results could actually bolster the argument that EPA-only treatment is superior to those that combine EPA and DHA. "That's the most obvious and logical conclusion," he said.

He explained further: "It may not be as simple as DHA neutralizing EPA in a 1:1 ratio. The biology is likely more complex than that. As well, it may not just be blood EPA levels that matter, but also how the EPA is delivered and how tissue levels are achieved, and the formulation tested in STRENGTH may not have been ideal in that regard."

Bhatt noted that the first author of STRENGTH, Stephen J. Nicholls, MD, has published research stating that EPA, and not DHA, is "where is the action is." Bhatt confirmed that when AstraZeneca announced the negative topline results for STRENGTH, he contacted the investigators and suggested the trial participants be offered the opportunity to receive icosapent ethyl instead, as it had just received the new FDA label. His offer was not accepted.


A discussant for the 2 trials, Alberico Catapano, PhD, said it was important to address the effect of the size the dose of icosapent ethyl, since it is 4 g of pure EPA without DHA. As for the effect of the mineral oil placebo, he said it was unclear whether that would fully explain the difference between the REDUCE-IT and STRENGTH results.

"Given the current uncertain state of knowledge, neither patients nor physicians can be confident that omega-3 fatty acids have any health benefits, yet in 2019 the global market for omega-3 fatty acids reached $4.1 billion and is expected to double by 2025," Deputy Editor Gregory Curfman, MD, wrote.

"To resolve the discrepancy between STRENGTH and REDUCE-IT, the FDA should require a postmarketing clinical trial of high-dose icosapent ethyl vs corn oil in patients at risk for cardiovascular events. This is a critical next step to shed further light on this perplexing clinical issue and research question."

Asked about the studies before Sunday's presentation, Lincoff said there are certain patients who should still take omega-3 fatty acids for other reasons, such as those with triglyceride levels above 500 mg/dL. When asked by 

® what clinicians should do if they are currently prescribing icosapent ethyl to patients, he said, the concern is that “none of the Vascepa trials have used neutral comparators.”

“It’s hard to say ‘take your patients off Vascepa,’ because there is a trial,” Lincoff said. “But I have a high threshold, at this point, to start patients on it.”

Nicholls SJ, Lincoff AM, Garcia M, et al. Effect of high-dose omega-3 fatty acids vs corn oil on major adverse cardiovascular events in patients at high cardiovascular risk: the STRENGTH randomized clinical trial. 

 Published online November 15, 2020. doi:10.1001/jama.2020.22258

The investigator of the STRENGTH study says findings raise questions about the landmark REDUCE-IT trial, but other evidence suggests the drugs involved are different.

Fish Oil Debate Continues as Study Finds No Risk Reduction From Omega-3 Combo

A new study presented today shows that 4 in 5 patients with 

 with reduced ejection fraction (HFrEF) could benefit from the sodium glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin, based on the label update the FDA approved earlier this year.

The findings, presented during the American Heart Association (AHA) Scientific Sessions and published in 

, are based on a study that applied the dapagliflozin label update against an AHA registry of more than 150,000 patients who had an initial hospitalization for heart failure.

, maker of dapagliflozin, the results are the first in a series of 6 studies that will come from TRANSLATE-HF. The platform will link data from the Get With the Guidelines Registry with CMS claims data, and researchers will track patients following hospitalization for heart failure. The TRANSLTE-HF research is supported by AstraZeneca, Novartis, Boehringer-Ingelheim, Lilly, Novo Nordisk, Sanofi, and Bayer.

Dapagliflozin, sold as Farxiga, is part of the SGLT2 inhibitor class that was first developed to treat type 2 

 (T2D). But after a round of cardiovascular outcomes trials showed the drugs significantly reduced hospitalization for heart failure, drug makers pursued their use to treat this condition whether or not patients had T2D.

, presented September 1, 2019, showed that dapagliflozin reduced the risk of worsening heart failure or cardiovascular death 26% regardless of diabetes status; the FDA approved the drug’s use to treat HFrEF in May 2020.

Although today’s results apply only to dapagliflozin, the authors note that findings for empagliflozin (Jardiance) presented during the European Society of Cardiology in August found similar efficacy in HFrEF, whether or not patients had T2D.

However, the lead author of TRANSLATE-HF and other experts have reported that not all patients who might benefit from SGLT2 inhibitors are receiving them.

“Despite accelerating scientific discoveries, few patients with heart failure are being treated with the best available treatment options in 2020,” lead author 

MD, MPH, and a cardiologist at Brigham and Women’s Hospital and Harvard Medical School, said in 

. “While SGLT2 inhibitors were first developed for treatment of diabetes, these therapies have now been recognized to reduce mortality, prevent worsening heart failure events, and improve health-related quality of life in patients with HFrEF, including among those without diabetes.”

In addition to showing the missed opportunity to treat more patients with heart failure generally, the results show that better awareness and greater willingness of cardiologists to prescribe SGLT2 inhibitors might help reach women and Black patients, who were less well represented in the DAPA-HF trial.

“Although there were more older adults, women, and Black patients in the [AHA] registry than in the DAPA-HF trial, most clinical characteristics were qualitatively similar between the 2 groups,” the study authors wrote, adding that compared with the DAPA-HF trial population, “there was lower use of evidence-based HF therapies,” among patients in the AHA registry.

that many cardiologists have been slow to embrace SGLT2 inhibitors because they still perceive the class as a “diabetes drug,” or they believe, erroneously, that prescribing them will cause them to become responsible for management of a patient’s glycated hemoglobin (A1C), even if the drugs are used to treat heart failure.

When cardiologists prescribe SGLT2 inhibitors, McGuire said communicating with other care providers is essential. This “engages the co-providers in a team approach,” so that the other providers understand that “we’re not stepping on their toes and we’re not embarking on glucose management in their clinic, but that we are using these medications for further cardiovascular benefits,” said McGuire.

“These data support the broad generalizability of recent trial findings evaluating the SGLT2 inhibitors to US clinical practice,” said Gregg C. Fonarow, MD, senior author of the study, who is interim chief of the division of cardiology and director of the Ahmanson-UCLA Cardiomyopathy Center, as well as co-director of the Preventative Cardiology Program, and the Eliot Corday Chair in Cardiovascular Medicine and Science at the University of California, Los Angeles. “The SGLT2 inhibitors are now established as a new pillar of care for patients with heart failure. We must now rapidly translate this knowledge to practice to improve patient outcomes.”

Vaduganathan M, Greene SJ, Zhang S, et al. Applicability of US Food and Drug Administration labeling for dapagliflozin to patients with heart failure with reduced ejection fraction in US clinical practice: he Get With the Guidelines–Heart Failure (GWTG-HF) Registry. 

A registry study suggests 4 in 5 patients with heart failure might benefit from the SGLT2 inhibitor dapagliflozin.

Four in Five HF Patients Could Benefit From Dapagliflozin, Registry Study Suggests

A new therapy that directly targets the heart function reduced the risk of hospitalization or emergency department visits in patients with 

 (HF) with reduced ejection fraction (HFrEF), according to a study released today.

Presented at American Heart Association Scientific Sessions 2020, the randomized, placebo-controlled, phase 3 Global Approach to Lowering Adverse Cardiac Outcomes through Improving Contractility in HF (GALACTIC-HF) trial sought to assess whether omecamtiv mecarbil, from Amgen, would lower the risk of HF events and cardiovascular death in patients with HFrEF.

Findings from the GALACTIC-HF trial were simultaneously published in the 

HFrEF is characterized by the decrease in systolic function and cardiac output, and to date, no medication works directly to boost systolic function and improve outcomes. In fact, many therapies studied even increased the risk of mortality.


However, a new class of therapies, called cardiac myosin activators, have shown promise in improving myocardial function by directly augmenting cardiac contractility. The first in the class, omecamtiv mecarbil, when given in short-term intravenous administration, was shown to improve cardiac performance in early clinical studies.


Moreover, patients with HFrEF administered omecamtiv mecarbil for 20 weeks were shown to exhibit increases in left ventricular systolic ejection time and stroke volume, decreases in left ventricular systolic and diastolic volumes (indicating beneficial reverse cardiac remodeling), and reduced plasma natriuretic peptide levels and heart rate.


Collecting a patient cohort of inpatients and outpatients (n = 8256) with symptomatic chronic HF and an ejection fraction ≤ 35%, researchers randomized (1:1 ratio) participants to receive omecamtiv 

 (25 mg, 37.5 mg, or 50 mg twice daily) (n = 4120; 77.6% White; 78.8% male) or placebo (n = 4112; 77.8% White; 78.7% male), in addition to standard HF therapy.

The study examined the primary outcome of a composite of a HF event (urgent clinic visit, emergency department visit, or hospitalization) or cardiovascular death, whichever occurred first, in a time-to-event analysis, with secondary outcomes assessing:

change in total symptom score on the Kansas City Cardiomyopathy Questionnaire (KCCQ) from baseline to week 24

After a median of 21.8 months, a primary outcome event occurred in 1523 of 4120 patients (37%) administered omecamtiv mecarbil and in 1607 of 4112 patients (37%) in the placebo group, indicating a signficant 8% risk reduction in incidence of a composite of a HF event or death from cardiovascular causes (hazard ratio (HR) = 0.92; 95% CI, 0.86–0.99; 

In assessing secondary outcomes, a similar 808 patients (19.6%) from the omecamtiv mecarbil group and 798 patients (19.4%) of the placebo group died from cardiovascular causes (HR = 1.01; 95% CI, 0.92–1.11). No significant difference was observed between groups in the change from baseline on the KCCQ total symptom score.

First hospitalization for HF exhibited a HR of 0.95 (95% CI, 0.87–1.03) for those in the omecamtiv mecarbil group compared with the placebo group, with death from any cause shown to be similar across both groups (HR = 1.00; 95% CI, 0.92–1.09). There was a 7% lower risk of a first HF event among patients administered omecamtiv mecarbil (n = 1177; 28.6%) compared with placebo (n = 1236; 30.1%), but this finding was not statistically significant (HR = 0.93; 95% CI, 0.86–1.00).

Researchers additionally were interested in examining the effects of omecamtiv mecarbil on vital signs, in which no difference was shown between groups in the change of systolic blood pressure between baseline and 24 or 48 weeks. Although, the change from baseline for the medican N-terminal pro-B–type natriuretic peptide level was shown to be 10% lower in the omecamtiv mecarbil group than in the placebo group.

The investigators noted that the drug was particularly effective for patients with lower ejection fraction. 

“The benefit was consistent across most subgroups, but a possible heterogeneity of effect was suggested by a potentially greater treatment effect in patients with an ejection fraction of 28% or less than in those with an ejection fraction of more than 28%,” they wrote.

The latest research adds to the plethora of emerging medications in the treatment of HFrEF. In comparison with findings from the 

, which assessed the same primary outcome of a composite of a HF event or death from cardiovascular causes for vericiguat, an oral soluble guanylate cyclase stimulator, the relative risk reduction of 8% in the GALACTIC-HF trial is lower than that of vericiguat (10% relative risk reduction). 

As with GALACTIC-HF, the VICTORIA trial found that results for vericiguat were different in some subgroups. 


So, what distinguishable benefits may omecamtiv mecarbil provide patients with HFrEF?

Paul Heidenreich, MD, MS, professor of cardiovascular medicine at Stanford University, commented during the presentation that it “remains to be investigated and discussed about exactly where omecamtiv mecarbil will fit in.”

However, Heidenreich notes that there are several promising signs for omecamtiv mecarbil, particularly how it causes no reduction in blood pressure. “Often this is a major limiting factor for many patients with HF who cannot tolerate some of those other therapies–this might be an option.”


Teerlink JR, Diaz R, Felker GM, et al. Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure. 

. Published online November 13, 2020. doi:10.1056/NEJMoa2025797

Findings from the GALACTIC-HF trial presented at AHA Scientific Sessions 2020 showed that patients with heart failure (HF) with reduced ejection fraction who took omecamtiv mecarbil showed a significant 8% relative risk reduction in a composite of a HF event or death from cardiovascular causes, compared with those taking placebo.

Omecamtiv Mecarbil Shown to Improve Cardiac Function, Clinical Outcomes in GALACTIC-HF

For a time, managed care preached that patients should pay some part of every service or medication they receive, lest they not have “skin in the game.”

But A. Mark Fendrick, MD, director of the Center for Value-Based Insurance Design at the University of Michigan and co-editor-in-chief of 

®, feels that there are some services, screenings, and medications that are so essential to life and health—and so key to avoiding long-term costs—that it’s cost-effective to skip out-of-pocket costs altogether.

It starts with identifying “high value” and “low value” care, because eliminating waste can pay for the screenings that save lives down the road, Fendrick said. In oncology, he said making these distinctions is hard work and takes courage, as he led a discussion on the state of value-based insurance design (VBID) in oncology, during the second day of the Community Oncology Alliance Payer Exchange Summit. Joining Fendrick were:

Neil Goldfarb, president, CEO, Greater Philadelphia Business Coalition on Health

Alti Rahman, MHA, MBA, CSSBB, practice administrator, Oncology Consultants

Barry Russo, MBA, CEO, The Center for Cancer and Blood Disorders, based in Forth Worth, Texas

“I like to think VBID is the new skin in the game,” Fendrick said, explaining that while it did not take a pandemic to show the importance of the idea, the effects of coronavirus disease 2019 (COVID-19) on oncology practices certainly highlight the need to tear down every barrier to cancer screening, as attendees heard evidence of skipped mammograms and colorectal cancer screenings—which, in turn, have led to patients showing up now with more advanced cancers.

Ending cost-sharing for key cancer screenings was a big win for VBID in the Affordable Care Act (ACA), but Fendrick said the work wasn’t done: more recently, the center has worked to implement an Internal Revenue Service rule that allows services and drugs for certain chronic conditions to be coverage “pre-deductible.”

“As everyone in the oncology field knows, when the year turns and deductibles reset our oncology patients are really in very tough financial terms,” he said, as patients often had to pay list price for cancer drugs, even if they’ve been taking them for a while. CMS has slowly incorporated more VBID concepts into more payment designs, including some for 2021.

“I’m curious to see how the oncology community would feel about a more nuanced approach to spending,” Fendrick said.

Goldfarb said he’s endorsed VBID for some time, but the challenge for employers is, “How do you actually go about doing this?” And even if VBID designs bring savings, is it worth the effort? Overcoming inertia is tough, he said, in part because, “We don’t necessarily know what is high-value or low-value care in oncology, particularly when we get beyond prevention to treatment and survivorship.”

Rahman said there are multiple considerations:

(1) getting VBID to work requires sharing information, and there are federal and state laws that can limit transfer;

(2) the transition of financial risk cannot be “passive,” because the decision-making drives movement toward high-value care;

(3) more transparency is needed, because “it’s still very difficult for patients to understand what they’re paying for; and

(4) much of what affects cancer care happens first in primary care or other specialty care, and while there are alternative payment models in these areas, they aren’t yet aligned with oncology models.

The mixed progress means that patients can still face huge out-of-pocket costs, which Fendrick says leads to results that no one should find acceptable. “I just think that my patient should not have to have a bake sale, or start a Kickstarter campaign to be able to get a cancer drug that she and her oncologist agree was designed specifically to treat her tumor,” he said.

But Russo said the hunt for cost savings, aided by technology, can yield insights of “low-value care” that would go undiscovered without the pressure of shared risk. “Clearly, there's some low hanging fruit that's easy to identify. But then when you get into the weeds, it's going to be a whole lot more complicated. And the definition of that really evolves,” he said.

Community Oncology Alliance

Value-based insurance design has made gains in oncology, but there's more work to do.

Bringing Value-Based Insurance Design to Oncology: The New “Skin in the Game”

White-bagging. Brown-bagging. Step therapy. Home infusion. Each term in the roster of payer cost-saving strategies means something different, but for the panelists taking part in Wednesday’s session at the Community Oncology Alliance Payer Exchange Summit, the bottom line was the same:

Taking control away from oncologists can lead to waste, can cost patients time and money, and can be downright dangerous.

COA Executive Director Ted Okon, MBA, moderated the panel featuring Michael Diaz, MD, director of Patient Advocacy, Florida Cancer Specialists & Research Institute; Janelle Hamilton, director of Payer Relations, and compliance officer, Illinois Cancer Care, PC; and Barbara McAneny, MC, chief executive officer, New Mexico Hematology Consultants, Ltd.

With Diaz, the current president of COA, and McAneny, a recent president of the American Medical Association, on the panel, no one held back with their thoughts how cost-saving efforts, however well-intentioned, can backfire and do harm.

“You just need to get medicine to the patient in time to be able to start treatment sometimes in a very timely fashion. Not all cancers are slow growing, and some are fast growing, and every day that you wait sometimes makes a huge difference in patients or patient outcomes,” Diaz said. “So, I just look at it as it's going to interfere with the quality and the value of patients care overall.”

Okon and the panel reviewed the various strategies:

refers to specialty pharmacies sending prefilled oncology therapeutics directly to the oncology practice; thus, if the physician needs to adjust the dose, the drug must be shipped back to the pharmacy.

occurs when drugs are sent directly to the patient, who must store them properly and bring them to the physician office to be administered.

which Okon and fellow panelists called “fail first,” requires patients in commercial and some Medicare Advantage plans to take oncology drugs or supportive therapies that may not be what their doctor prescribes and see that they do not work before getting the preferred treatment. Okon pointed out that the first drug given may not be the cheapest, but may be the one that brings the biggest profit for the payer.

calls for oncology drugs to be given outside an infusion center, by a nurse who may or may not be a certified oncology nurse. The physicians on the panel objected strongly to this practice, because they said a single nurse is not equipped to manage an adverse reaction.

Okon asked McAneny to address problems with white-bagging, especially when the oncologist needs to adjust a patient’s regimen. “The issue with white bagging is that if the insurance company has sent me that drug and that dose, if I need to change that patient's dose for any reason, or even change to another regimen altogether, because the patient has progressed or isn't tolerating the first regimen, then I have to send that patient away, and bear the cost of sending that drug back to whoever sent it to me. And then the patient would have to wait until the new drug is approved and come in, and then make another trip," she said.

McAneny, who has patients who may travel 100 miles to see her, said this costly to patients and caregivers. “I think one of the things that needs to be considered—that's almost never considered when insurers are making these changes—is the effect on the patient's out-of-pocket expense. … If that patient has to go away, and come back another day, they have to take the daughter out of work again, maybe take the kid out of school, again, make other arrangements to get transportation, it really is going to increase the inequities that we see for poor people vs wealthier people.”

When oncologists cannot manage the drugs themselves, they don’t know who has mixed it, or whether it’s been kept at the right temperature during shipment, she said. “I think this is an insurance company sacrificing patient safety, for expedience, and the hope that this will somehow save them money.”

If the drug arrives and doesn’t look right, McAneny said she will not use it. Brown-bagging is even worse, she said, because patients can leave drugs in their car where they are exposed to heat.

Hamilton said that physicians in her practice have worked to reach patients by traveling out to rural areas of Illinois once a week. “So, if that drug is not there, or that dosage changes, and we’re not back in that clinic for another week, we stand to delay that treatment,” she said, adding that she’s succeeded in changing one payer contract to allow the clinic’s physicians to buy-and-bill to avoid this circumstance. But that’s just one contract.

Diaz said the situation threatens the trust that doctors work to establish with patients. “They want to get their value, but they’re also concerned about their safety,” he said.

One patient told the mail order pharmacy to stop sending his oral medication with a cold pack, and the Florida clinic started seeing detectable levels of cancer in his bloodwork. The clinic was unaware of the patient’s instructions to stop shipping with the cold pack. Patients assume the insurer always does things that are in their interest, but that’s not always the case, Diaz said.

McAneny said the mail-order system leads to waste, because patients often continue to receive drugs after their regimen or dose has changed. At her New Mexico clinic, McAneny instructs patients to bring unused therapies to her office—and once she took the wasted treatments to a meeting with a payer.

“I took that box with me and I dumped it out on the desk and said, ‘Here's $300,000 worth of drugs that you paid for, that our patients could not take.’ And they decided that maybe they would let us buy-and-bill and supply those medications,” McAneny said.

Okon and Diaz then discussed problems with step therapy. “I never want to say step therapy without saying, ‘fail first.’ Because that’s what step therapy is.” He said the use of step therapy has expanded beyond its original intent, with pharmacy benefit managers dictating which drug must be used, and Diaz calling it, “practicing medicine without a license.”

Step therapy is especially problematic when patients are denied supportive treatments to control pain or nausea, or forced to take more toxic therapies their physicians know will make them sick. “We have a hard time managing pain anyway,” Hamilton said. “And a delay to get adequate pain control because you're limited to the amount of which drug that you can start with has been an issue.”

Payers have put mandates on sleeping medications, anticoagulants, or required iron formulations that require 10 trips to the clinic instead of 2, the panelists said. This doesn’t take the inconvenience of the patient into account, they said. Diaz said some payers literally require patients to violently throw up before they will cover medication to prevent nausea. If patients who are likely to become ill don’t get this treatment up front, there’s a good chance they might not get any more chemotherapy.

Besides being costly to practices, McAneny said putting physicians through these hoops contributes to physician burnout. “One of the things that we have seen across the country is that physicians would like to spend time with patients we know that for every hour they spend with patients, they get to spend two hours with a computer. And now they probably get to spend another half an hour talking to someone who knows nothing sometimes about oncology and is just reciting the payer’s policy from their manual at you,” she said.

“I think these policies are incredibly shortsighted,” McAneny said, noting the growing shortage of oncologists. “They're sacrificing perhaps short-term profits, perhaps short-term savings, for a long-term negative impact on the health care delivery system.”

Home infusion was controversial before COVID-19, but it has gained attention because some payers have promoted it as a way to keep patients from traveling to infusion centers. McAneny believes this is shortsighted. A person’s bedroom or bathroom is likely not as sterile as an infusion center, and there’s no way of knowing if a nurse is entering a house where someone has been exposed to the virus.

A viewer asked whether payers, including Medicare, are listening to physician concerns. Hamilton answered first. “I don’t think that they're listening to us. I think we'll probably see more and more step therapy, and [similar] things being put into place. You know, I look at things on the physician side, we're seeing it on both the pharmacy and [on] the physician, which are, which are two different contracts and two different people to deal with.”

Panelists at the Community Oncology Alliance Payer Exchange Summit take issue with strategies they say harm patients and don't save money in the long run.

When Payers’ “Cost-Saving” Steps Don’t Help Patients

Bhuvana Sagar, MD, a national medical executive with Cigna Health Care, gave her insight on successfully implementing payment reform models in oncology after participating in the session "Deep Dive: Updates From Three Ongoing Oncology Payment Reform Projects" at the 2020 Community Oncology Alliance Payer Exchange Summit.    

The word “evolving” came up several times during the discussion with regard to making models work over time for oncology providers. Given Cigna’s national footprint, how do you strike the right balance between a standard you can scale and making period changes to reflect the feedback you receive?

That's a very good question. I think overall, a lot of things that apply to community oncology do not apply to hospital-based practices. As you know, the practice setting is different. The methodology is different, the way the physicians operate is different; some of these institutions are NCCN [National Comprehensive Cancer Network], or NCI [National Cancer Institute] cancer centers, [so] the way they manage care is a little bit different from the way our community oncology practices manage care. So, over the years, and initially, our initial model was [introduced in] 2015. Our model was primarily like an Oncology Medical Home. We were a little ambitious, we had a lot of risk adjustment built into the model to understand cost differences that can be accounted for by  advanced stage disease or early stage disease. We've also looked into doing a total medical cost model with episodes. So we've looked at the entire gamut, we get feedback, and it is not an easy thing to do on our side. Also, we also have a lot of administrative burden as we've done and as we do try to operationalize these models. So it does take a lot of effort on our end, to get the feedback in to make the changes necessary. And then there's a lot of contracting language that goes into play and several folks that work on the model to make things happen. So I would say that it's not an easy task. But we do try to get feedback from all the providers ... how Florida practices [is] not exactly how New Jersey practices. So we did take those comments into count as we do that.

You mentioned that the feedback you get from community providers may be different from hospital/facility providers. What are some specific differences that these groups raise in implementing your model?

[At] a lot of these large institutions, they have an entire division that works on breast cancer, for example. So they have breast cancer division, the lung cancer division, and each division operates a little bit differently. And ideally, when we implement models, we like to have like a single point of contact that is available to connect with our clinical resource or non-clinical resource, so that there's that collaboration between the two of us, [the payer and] the provider as we move this forward. So, you know, we've experienced some challenges because of the way they are set up, and how their operations are set up. And so they may, they don't necessarily have one nurse, they have probably 50 different nurses that [perform] that function of navigator or coordinator, so to speak. That's just one tiny sliver of things. But I think a lot of the big hospitals, they also have a consistent pathways or consistent methodology, the way they operate, they also have greater access to clinical trials. Community oncology functions a little bit differently. [Many] times are able to provide that single point of contact. [Often] their physician leadership is very closely engaged with our teams. They also have team-based care where the teams are smaller, the scales are much larger in a hospital based system. I think that's probably like the best description I can give.

Your comment about reducing administrative burdens and limiting measures to only those that are necessary was well-received. Is there a specific method Cigna is using to identify burdensome steps/measures/processes?

So, when we started initially, we came up before OCM [Oncology Care Model] came out. And so we had reasonable measures and once OCM came out, we tried to align as much as possible with OCM to make it easier on providers. That being said, any minor change in the measure itself, measure definition, makes it a completely new measure. So OCM has a different methodology for collecting data from providers, and obviously, we as Cigna Health Care, [don't have] the resources that CMS has to be able to get that level of detail. So what we had to do was, at that point, once we made the changes, and we had to [take another look] at them, understanding the challenges providers had in submitting some of these codes, and [ask], are they suffering pain management, for example, depression screening, are they doing adequate depression screening and addressing those challenges with patients? 

So, we tried to simplify at that point to say, OK, we will accept additional quality certification. We've tried to simplify as much as possible, but there's always administrative burden with any of these value-based care models we're trying to do, because you're trying to change the way we practice and we operate as a oncology ecosystem. So, I think we have made significant progress, I believe. But I think like as any change you make, like I told you is going to make a change in our model and contracting language, things like that. So, overall, we do take into account feedback. We  can't always respond to every single [piece of] feedback, but we do make reasonable changes and try to simplify things because it's important for us to keep it simple and standardized because we are a national payer. We want to make sure that it's a model that we can operate and implement and do it with as little burden as possible. 

Videos

Bhuvana Sagar, MD, national medical executive, Cigna Health Care, offers insights on implementing payment reform models in oncology after a session at the 2020 Community Oncology Alliance Payer Exchange Summit. 

Dr Bhuvana Sagar Discusses Payment Reform in Oncology

Lalan Wilfong, MD, executive vice president for quality programs and value-based care at Texas Oncology and Community Oncology Alliance payment reform co-chair, discussed the role of employers in cancer care benefits and issues stemming from the pandemic ahead of his appearance on the panel "Assessing Provider Quality & Value in Cancer Care: What Should Employers & Self-Funded Companies Be Looking For?" at the Community Oncology Alliance Payer Exchange Summit.

You are appearing on a panel addressing employer involvement in oncology benefits. How is employer involvement in cancer care changing?

Cancer care used to be off the radar for most employers. It fell far below musculoskeletal disorders, for example, in what their employees sought health care for. Now, with the growing incidence of cancer and the the cost of cancer care rising so rapidly, it's starting to hit the radar screens of employers as the significant cost driver for their healthcare book of business. So so the employers are being tasked with looking at cancer care, because it is hitting their balance sheets more for the cause, and trying to understand what they are paying for for that cancer care is a good quality care and are they getting the best value for the money they're spending on their employees with cancer?

What specific concerns to employers have about cancer diagnoses or deferred care during the pandemic?

The biggest concern that employers should have about this is the delay in diagnoses. We know that a screening mammography screening colonoscopies, for example, can catch cancers early where they are much more easily treated. And so employees can get treated and get back to work very quickly, versus waiting for that cancer to progress and present at a later stage, which then has negative impacts on patient survival, as well as people's productivity because the treatment protocols can be much more onerous on patients as their cancer as their cancer stage is higher.

 study highlighted the fallout from delayed screenings during the first months of the pandemic. Can employers take steps to reduce the ongoing impact?

Definitely. There's a role for employers in helping their employees do cancer screenings. One is just education about that, making sure that they understand that even during the pandemic, that cancer screenings may be appropriate for them, encouraging them to talk to their physician about that screening and make sure it remains appropriate for them during this time. And then finally, I think the biggest thing is in benefit design, making sure employees have no obstacles to those appropriate cancer screenings so they can get them appropriately.

Lalan Wilfong, MD, executive vice president for quality programs and value-based care at Texas Oncology and Community Oncology Alliance payment reform co-chair, discusses the role of employers in cancer care benefits and issues stemming from the pandemic.

Dr Lalan Wilfong Talks Employer Involvement in Cancer Care Benefits

At this year’s Community Oncology Alliance (COA) Virtual Payer Exchange Summit, the conversation on driving change within cancer care and cost reduction involves not only community-based oncology practices, but the 

 and employer health groups who work with them as well.

 of the American population receiving health insurance through their employers, this year’s 

 placed a distinct focus on the role of these organizations, particularly how they can improve the quality, experience, and cost of cancer care.


However, as cancer care, or even general health care, is not typically the expertise of employers nationwide, how can these groups initiate change in a system they may not fully understand?


“Assessing Provider Quality & Value in Cancer Care: What Should Employers & Self-Funded Companies Be Looking For,”

 on day 1 of the 2020 COA Virtual Payer Exchange Summit, moderator Robert Baird Jr, RN, MSA, president of the National Cancer Treatment Alliance, opened the discussion by first asking  Lalan Wilfong, MD, executive vice president of Value-Based Care & Quality Programs at Texas Oncology and COA Payment Reform co-chair, what signifies value and quality in oncology.


Wilfong, who was joined on the panel by John Fox, MD, chief boundary spanner at Foxworthy Healthcare Consulting LLC, and Lee Schwartzberg, MD, FACP, executive director at the West Cancer Center & Research Institute, discussed that while many major cancer centers advertise the quality of the care they provide, none have defined exactly what quality is.

“Is it access in getting patients in on a timely fashion? Is it following national standard guidelines? Is it patient outcomes, such as hospitalizations and emergency department visits....I think there's a lot of different aspects that go into what defines a good quality oncology experience for a patient, but it's hard to define that in a granular fashion to show that you are a good quality practice,” said Wilfong.


Building on the definition of quality in cancer care, Schwartzberg credited the introduction of the Oncology Care Model (OCM) in helping his organization delineate patient needs and pressure points to address from a quality perspective. Focusing primarily on reducing costs and improving the care process, he says that for those oncology practices who have addressed these concerns, a transition to outcomes that matter to employers, such as return to work or return to work for caregivers, is warranted.


While outcomes like overall survival may serve as the basis of quality assessment in clinical trials, from an employer perspective, it may not be as important as employees may not stay with their respective employers for an extended period of time, explained Schwartzberg. “I think we need to really dialogue with our employers and see what they feel are really tangible, important, quality metrics beyond what we've done already.”


A panel of key opinion leaders discuss how employers and self-funded companies should assess provider quality and value in cancer care at the 2020 Community Oncology Alliance Virtual Payer Exchange Summit. 

Latest Conference Articles