Mary Caffrey

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FDA’s role in approving of one or more coronavirus vaccines—especially before the Election Day November 3—came under fresh scrutiny this weekend, amid reports that HHS Secretary Alex Azar has asserted greater control over the agency and Commissioner Stephen Hahn, MD, was blocked from testifying before Congress.

 that Azar issued a memo on Tuesday barring the nation’s top health agencies, including FDA, from having the last word on any new rules on food, drugs, medical devices, or other products, which would include vaccines. 

 said it had obtained the memo, which said that final sign off “is reserved for the secretary.”

The report said the memo did not make clear whether the process for evaluating and approving vaccines for coronavirus disease 2019 (COVID-19) would be altered. Three such vaccines are in phase 3 clinical trials. News of the memo comes as AstraZeneca, one of the companies with a vaccine in late-stage development, 

 of its trial over the weekend, following two separate halts following adverse events in trial participants. The study has resumed elsewhere but is still on hold in the United States, according to 

Observers familiar with the FDA warned that this latest episode would only fuel public fears that political concerns, not science, were driving vaccine development. On September 8, pharmaceutical companies behind leading vaccine candidates responded by 

 that they would “only submit for approval or emergency use authorization after demonstrating safety and efficacy through a Phase 3 clinical study that is designed and conducted to meet requirements of expert regulatory authorities such as FDA.” Besides AstraZeneca, those signing include Pfizer, Moderna, Johnson and Johnson, and Sanofi.

Peter Lurie, MD, MPH, president of the Center for Science in the Public Interest, told 

 the new policy was “a power grab” that could slow routine regulatory processes. Lurie is a former associate commissioner of the FDA.

The FDA memo comes the same week that the Trump administration, under pressure, withdrew a heavily criticized CDC guideline on COVID-19 testing after it was revealed the document had been posted on the agency’s website over the objection of its scientists.

 Meanwhile Friday, two Democrats from the House Energy and Commerce Committee issued a 

 saying the White House had blocked FDA’s Hahn from testifying before their panel with a scheduled update on the agency’s response to COVID-19.

Chairman Frank Pallone, D-New Jersey, and Health Subcommittee Chair Anna Eshoo, D-California, said in their statement, “The American people deserve to hear Commissioner Hahn’s response to those concerns during a public hearing and what actions he is taking to ensure that the agency’s COVID-19 decisions remain science-based. The White House’s muzzling of the FDA’s top scientist further injures public trust and confidence in FDA.”

Hahn did appear Friday on Twitter: “I am often asked about how and when FDA will authorize or approve a vaccine to protect against COVID-19. Here is my answer: when the agency’s scientific experts have completed their review and are ready to do so, and not a moment before.”

Articles

Reports say Azar is asserting control over FDA as vaccine trials near completion, while Hahn is blocked from testifying on COVID-19.

FDA Update: Report Claims “Power Grab,” Dems Say Hahn Blocked From Testifying

The coronavirus disease 2019 (COVID-19) pandemic forced the European Society of Cardiology to present its 2020 Congress (August 28-September 1) in a virtual format; by some accounts, this was a rousing success—the ESC did not charge for participation and reported online attendance of 116,000, with its largest female audience ever. More than half the participants were under age 40, the Congress reported in a 

. That’s not to say there weren’t a few snags. But the science was top notch, with many implications for clinical practice and regulatory approvals. Here are 5 takeaways from the 2020 Congress:

SGLT2 inhibitors were the star of the show.

 in Farxiga (dapagliflozin) were the top draws; topline results announced ahead of the meeting indicated these trials would be home runs, and they did not disappoint. EMPEROR-Reduced (for heart failure with reduced ejection fraction) showed the sodium glucose co-transporter 2 (SGLT2) inhibitor cut the risk of cardiovascular death or hospitalization for heart failure by 25% and first or future heart failure hospitalizations by 30%. DAPA-CKD showed a 39% drop in the risk of renal decline or kidney failure death. As discussed in the 

®, experts spoke of the results together as proof that the drug class has moved well beyond its roots in diabetes care; one commentator called it an “organ protection “ class.

Will a combination for HFpEF come in 2021? 

After the PARAGON-HF trial for Entresto (sacubitril/valsartan, Novartis) just missed its end point for heart failure with preserved ejection fraction (HFpEF) in 2019, cardiologists wondered if this hard-to-treat condition would ever have an approved therapy. This weekend, the PARALLAX trial hit its mark on a key biomarker end point but missed on the 6-minute walk test. (FDA is reviewing Entresto in HFpEF.) But there’s more to the story. Patients in EMPEROR-Reduced taking both Entresto and Jardiance showed this combination can work well together, and the lead investigator for PARALLAX said 

 that when trial results for EMPEROR-Preserved appear next year, a four-drug combination including Entresto and an SGLT2 inhibitor may finally offer a HFpEF solution.

One of the weekend’s true bright spots was the presentation from Italy’s Iacopo Olivotto, MD, who told listeners that after 60 years of trying, it was hard to describe the feeling among the scientific community about mavacamten, a drug that appears to be working for patients with hypertrophic cardiopmyopathy (HCM). This genetic condition causes too many heart contractions, which leads to thickening, shortness of breath, fatigue, and sometimes sudden death. Phase 3 results in EXPLORER-HCM showed that twice as many patients taking the drug hit clinical and functional benchmarks as those taking placebo. It’s expected that MyoKardia, the maker of mavacamten, make seek FDA approval in early 2021.

New guidelines, including a first for sports. 

The annual ESC Congress is well-known for its release of guideline updates, and 2020 was no exception. This year’s updates came in management of 

 in patients presenting without ST-segment elevation, management of 

. For the first time, ESC released guidelines in 

 and exercise for patients with cardiovascular disease. Unlike prior position statements that focused on avoiding sudden cardiac death in athletes, these new guidelines are designed to integrate sports and physical activity into a health plan for patients with cardiovascular disease, thus addressing epidemics of obesity, diabetes, and heart disease.

COVID-19 doesn’t just affect meetings—it’s affecting results. 

The ESC organizers did their best to give the original host city of Amsterdam attention in pre-taped travelogues, and the studio that hosted the “hot line” presentations set the bar for production values. But there were glitches here and there, and results like the breakthrough EXPLORER-HCM data missed the thunderous applause they deserved. More troubling was the notation in the EMPEROR-Reduced findings that 42 patients were lost to follow-up due to COVID-19 chaos, and one must wonder what will happen to key heart failure trials now in the pipeline. And on the heels of ESC came word that another major heart event—the American College of Cardiology—will move its annual meeting slot of mid-March to 

, with the hope of boosting in-person attendance.

The 2020 meeting, presented in a virtual format from its original host city of Amsterdam, The Netherlands, had lots of important science and a record number of viewers.

5 Takeaways From the European Society of Cardiology 2020 Congress

Heart patients can safely keep taking angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) if they are hospitalized with coronavirus disease 2019 (COVID-19), based on findings from the first randomized trial to study this issue.

 trial, presented Tuesday during the European Society of Cardiology meeting, found no difference between patients who kept taking their ACE inhibitors or ARBs and those who stopped taking them for 30 days after being diagnosed with COVID-19. The study, led by Renato Lopes, MD, PhD, of the Duke Clinical Research Institute, Durham, North Carolina, involved 659 patients at 29 sites in Brazil.

Patients were followed for 30 days after diagnosis. Results showed that the average number of days alive and out of hospital was 21.9 for patients who stopped their medication 22.9 for patients who continued them; the average difference in clinical status at 30 days between groups was -1.1 days.

“This is the first randomized data assessing the role of continuing versus stopping ACE inhibitors and ARBs in patients with COVID-19,” said Lopes. “Because these data indicate that there is no clinical benefit from routinely suspending these medications in hospitalized patients with mild to moderate COVID-19, they should be generally continued for those with an indication.”

The results confirm the early recommendations from major professional societies that patients should keep taking their medications, he said.

Since the COVID-19 pandemic began, clinicians have grappled with the question of whether to continue giving patients these medications. Associations between angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2 were a concern, as ACE2 was seen as a port of entry for the virus that causes COVID-19, and thus could make COVID-19 more dangerous in some patients. Yet other evidence suggested that renin-angiotensin-aldosterone system inhibitors could reduce acute lung damage from COVID-19.

Researchers excluded patients who were using more than 3 antihypertensive drugs, or sacubitril/valsartan, or who were hemodynamically unstable at hospital admission.

Lopes told reporters during a press briefing that the trial also examined several secondary end points, including myocardial infarction and stroke and how far the disease had progressed, as measured by whether a patient was intubated or in the intensive care unit. “Basically, the results are very consistent,” he said. “We do not see any significant difference between treatment strategies in any of the key secondary end points that were also assessed in the trial.”

More results on subgroup analyses, such as results by age or for obese patients, will be presented later, he said.

A study from the European Society of Cardiology answers a question about COVID-19: should patients keep taking well-known heart medications?

Duke Scientist: Patients With COVID-19 Should Stay on ACE Inhibitors, ARBs

Researchers in Sweden have found that children diagnosed with celiac disease have a 19% higher risk of receiving a psychiatric diagnosis as adults, especially for eating and mood disorders, attention-deficit hyperactivity disorder (ADHD), and autism.

 Clinical Gastroenterology and Hepatology.

, a database of health records from more than 19,000 children in Sweden created from 2015 to 2017 to study gastrointestinal illnesses. Data from 1973 through 2016 was culled from 28 sites, and researchers matched each patient with up to five reference controls.

Over a median follow-up time of 12.3 years, 3174 children (16.5%) who had celiac disease were diagnosed with a psychiatric disorder, compared with 14.1% of the patients in the control group. Corresponding incidence rates of psychiatric disorders were also higher among the children with celiac disease.

A person with celiac disease has an immune reaction to eating gluten, a common protein found in wheat, barley, and rye. Gluten triggers inflammation in the small intestine lining, causing bloating, gas, fatigue, and diarrhea; over time, the person is unable to absorb nutrients, and some may experience osteoporosis. Dietary changes to avoid gluten are recommended.

The greatest risk of a psychiatric diagnosis appeared in the first year after celiac diagnosis (HR, 1.70; 95% CI, 1.41-2.05). But the risk remained as children reached adulthood, and the authors reported the celiac patients were at particularly high risk of certain disorders:

Mood disorders (hazard ratio [HR],1.20; 95% CI, 1.12-1.28)

Eating disorders (HR, 1.34; 95% CI, 1.18-1.51)

Autism spectrum disorder (HR, 1.47; 95% CI, 1.32-1.64)

There was significant link between celiac disease and psychotic disorders, personality disorders, behavioral disorders, or suicide. Researchers did find that childhood celiac disease was associated with a greater likelihood to use psychiatric drugs in adulthood.

Researchers evaluated records to study only children with celiac disease who also had siblings, and the siblings without celiac disease had no higher risk of psychiatric disorders than the general population. Also, the team evaluated children diagnosed with a psychiatric disorder before the diagnosis with celiac disease; they concluded that while the stress of following a gluten-free diet might account for some level of depression or anxiety, it did not fully account for their findings.

 published in May found increased levels of depression and anxiety among 50 children newly diagnosed with celiac disease—as well as their parents—compared with a control group.

Due to their findings, authors of the Swedish study wrote, “Mental health surveillance should be integral in the care of celiac disease.”

Celiac disease was linked with a greater likelihood to be diagnosed with a mood disorder, ADHD, or an eating disorder.

Author | Mary Caffrey

Articles

FDA Update: Report Claims “Power Grab,” Dems Say Hahn Blocked From Testifying

5 Takeaways From the European Society of Cardiology 2020 Congress

Duke Scientist: Patients With COVID-19 Should Stay on ACE Inhibitors, ARBs

Swedish Population Study Links Celiac Disease With Higher Risk of Psychiatric Disorders