Kevin Kunzmann

Coinciding with the new presidential administration, the US medical community welcomed a change to leadership Wednesday.

Janet Woodcock, MD, has been appointed as acting commissioner of the US Food and Drug Administration (FDA), following the resignation of Stephen Hahn, MD, at the very end of the Trump administration.

Woodcock, a 35-year veteran in the FDA, currently serves as the agency’s Center for Drug Evaluation and Research (CDER) director. She also is a member of the 

 vaccine response team Operation Warp Speed.

In a note to the FDA staff Wednesday afternoon

, Woodcock expressed her personal pride in her role within the agency during the ongoing pandemic, thanking her team for enduring “hardships while carrying out our public health mission, balancing work and family, and trying to stay safe.”

“Every outside forum I interact in, people thank me profusely for the FDA and the work it is doing on their behalf,” Woodcock wrote. “I believe that life will improve in 2021, but I don’t know how quickly that will happen. The hope keeps me going.”

Woodcock also stressed that her recusal from FDA decision-making on products pertinent to Operation Warp Speed—excluding investigational vaccines or diagnostics seeking emergency authorization—will continue in her role as commissioner.

Woodcock replaces Hahn, the previous Chief Medical Officer of the MD Anderson Cancer Center, who had served in the position for 

 after the resignation of former Trump-appointed commissioner Scott Gottlieb, MD.

In his own message to the FDA staff today, Hahn highlighted the agency’s work in response to the pandemic under his leadership.

“Through it all, FDA employees have been critical in helping to respond to the disease with very real scientific advances like the authorization of the first nonprescription OTC [over the counter] Covid test, the authorization and approval of an anti-viral agent and the first two F.D.A. authorized Covid-19 vaccines,” Hahn wrote, 

Presumably, Hahn’s most memorable achievements while commissioner will be the FDA’s Emergency Use Authorization (EUA) granted to Pfizer’s BNT162b2, and Moderna’s mRNA-1273, the first vaccines indicated for the prevention of COVID-19.

Presently, the Biden administration has not indicated its timeline for appointing a new FDA commissioner. Gottlieb was appointed to the role in May 2017, following Trump’s inauguration that January.

Articles

The longtime FDA expert assumes the role following the resignation of Stephen Hahn, MD.

Janet Woodcock, MD, Appointed as Acting FDA Commissioner

The US Food and Drug Administration (FDA) has approved vericiguat (VERQUVO) for the reduced risk of cardiovascular death and heart failure hospitalization in patients who have received particular care for 

The indication marks the Merck therapy as the first granted for chronic heart failure patients who have been either hospitalized or need outpatient intravenous (IV) diuretics.

Vericiguat is a soluble guanylate cyclase (sGC) stimulant currently being developed in 2.5 mg, 5 mg, and 10 mg oral tablet doses.

When bound to nitric oxide, sGC catalyzes intracellular cyclic guanosine monophosphate (cGMP), which is involved in the regulation of vascular tone, cardiac contractility, and cardiac remodeling. HF has been linked to impaired synthesis of nitric oxide and therefore decreased sGC, which could contribute to myocardial and vascular dysfunction.

Merck investigators indicate that by stimulating sGC with vericiguat, regardless of nitric oxide status, the therapy can improve levels of cGMP, and provide patients with smooth muscle relaxation and vasodilation.

As stressed by phase 3 VICTORIA trial author Paul W. Armstrong, MD, Distinguished University Professor in the Department of Medicine at University of Alberta, in an interview with 

, vericiguat is a novel compound that provides a fairly unique avenue of HF treatment.

“A new compound, a new pathway, and an unmet need in a high-risk population was where we were headed,” Armstrong said.

The pivotal phase 3 VICTORIA trial’s data used in Merck’s application to the FDA was a randomized, controlled, double-blind, event-driven assessment across multiple clinical centers observed 10 mg once-daily vericiguat versus placebo in 5050 adult patients with symptomatic chronic HF.

The target maintenance dose of 10 mg once daily was increased from a 2.5 mg initial dose, raised in two-week intervals to 5 mg then 10 mg.

The disease was classified by New York Heart Association (NYHA) class II-IV definition and left ventricular ejection fraction <45% after a worsening HF event.

Armstrong and colleagues sought a primary endpoint of composite time to first event of cardiovascular death or hospitalization from HF.

Study participants were a mean age of 67 years old, with 76% being male and 64% being White. Mean LVEF was 29%, and about two-thirds of participants were enrolled within 3 months of a HF hospitalization index event. Median NT-pro B-type natriueritc peptide (NT-proBNP) levels were 2700 pg/mL at randomization.

At study baseline, 93% of participants were on a beta-blocker; 73% were receiving angiotensin-converting enzyme (ACE) inhibitors or an angiotensin II receptor blockers (ARB), and 70% were receiving a mineralocorticoid receptor antagonist (MRA).

At a median follow-up of 11 months, vericiguat was observed to be superior to placebo in reduced event risk based on time-to-event analysis. At approximately the same time period, 90% of patients in both treatment arms were treated with the 10 mg target maintenance dose.

Investigators observed an adverse event profile for vericiguat which was similar to placebo. Common adverse reactions to occur more frequently with the therapy included hypotension (16% of patients) and anemia (10%).

Maximum duration of vericiguat care via the VICTORIA trial was 2.6 years.

 at the time of VICTORIA phase 3 findings being presented at the American College of Cardiology (ACC) 2020 Virtual Sessions last year, Armstrong expressed hope that vericiguat would be the first therapy to “open a new pathway” of care for patients with chronic HF.

“We’re hopeful this would add value to the compection of heart failure treatment,” he said.

When considering its role in chronic HF prescribing, Armstrong stressed the significant rate of VICTORIA patients already on ACE inhibitors, ARBs, or with cardiac devices—who nonetheless were struggling to reduce risk of HF events. A proven, once-daily oral tablet contributes well to this burdened population.

“When you look epidemiologically, about 1 in 4 patients each year in the chronic HF population may qualify for this,” Armstrong said. “We’ve made a lot of strides in the advancement of heart failure, but seeing these patients at higher risk come through the gate, I think there is a need for something new. Vericiguat fits that bill.”

The approval is the first indication for a new pathway of care—one which has been linked to reduced heart failure death and hospitalization.

FDA Approves Vericiguat for Chronic Heart Failure

 polygenic risk scores may be the most beneficial of all related mood disorder risk scores in the assessment of 

The American Professional Society of ADHD and Related Disorders (APSARD) 2021 Annual Conference

 this weekend, a team of Massachusetts General Hospital investigators reported that such risk scores may even provide explanation into the significant comorbidity rate of ADHD and other youth mood and emotional dysregulation issues.

Presented by author Joseph Biederman, MD, the study sought to assess the available body of information available on associations between polygenic risk scores for bipolar disorder (BP-PRS) and pediatric bipolar spectrum and related disorders.

As Biederman and colleagues noted, the strong genetic basis of mood disorders could potentially provide clinicians with diagnostic insights when few avenues of care are clear.

“Because the genetic basis of complex disorders such as mood disorders is polygenic, clinically relevant information could emerge from genetic markers in aggregate in the form of polygenic risk scores,” they wrote.

Their research included an online literature search for the following grouped terms:

PRS and Bipolar Disorder, Bipolar, or Bipolar Depression

PRS and Attention, ADHD, Conduct Disorder symptoms, emotional dysregulation, aggression

The investigators additionally screened for predetermined inclusion and exclusion criteria.A litany of variables were extracted from relevant studies, including population age, study size, source of PRSs, source of clinical and genetic data, primary study outcome, assessments used, and main findings.

In their findings, Biederman and colleagues observed bipolar PRSs were significantly associated with deficits in executive functioning, ADHD diagnoses, and associated executive function deficits.

In the lone study to compare depression PRSs to bipolar PRSs directly in youths, investigators noted that, among the 40,000 children aged 6-17 years old, only depression PRSs were associated with ADHD symptoms, internalizing problems, and social problems.

ADHD PRSs, the team reported, were associated with conduct problems, depressive symptomatology, and externalizing disorders symptoms.

“Findings revealed that while higher BP-PRSs were correlated with increased hypomania scores, ADHD-PRSs were more clearly associated with emotional reactivity, emotional dysregulation, and irritability—frequent correlates of pediatric bipolar spectrum disorder,” investigators wrote.

Though depression PRSs were predictive of more severe pediatric trajectories toward major depressive disorder, their contribution toward pediatric bipolar spectrum and related disorders is still unknown; available studies did not examine such risk in observed patients.

Taken together, one form of polygenic risk scores seems to best inform interpretation of pediatric mood disorder risks and progression.

“These finding suggest that ADHD-PRSs may have the most important contribution to the development of mood related problems in youth and may begin to explain the high comorbidity between ADHD with mood and emotional dysregulation problems in the young,” Biederman and colleagues wrote.

The study, “Can Polygenic Risk Scores Help Identify Pediatric Bipolar Spectrum and Related Disorders?” was presented at APSARD 2021.

Such scores could provide insight into the significant comorbidity rate of ADHD and other youth mood and emotional dysregulation issues.

ADHD Polygenic Risk Scores May Benefit Pediatric Bipolar, Mood Disorder Understanding

A pilot study assessing the use of telemedicine in patient-reported responses to adult 

treatment showed a notable sensitivity to the impact of therapy changes on symptoms and patient functioning.

, investigators from Massachusetts General Hospital reported outcomes from an online survey-based assessment of adults with ADHD asked to gauge real-time response to psychopharmacology.

They observed a likely correlation to patient sensitivity and mobile ADHD symptom monitoring following changes in treatment status.

The Shire and Takeda-supported trial, presented by author Craig Surman, MD, included 90-plus patients aged 18-80 who self-identified a taking stimulant therapy for ADHD. Participants recorded their demographic information, medication use history and patterns, and their symptoms associated with ADHD.

Surman and colleagues used mobile phone surveys and messaging systems from RedCAP to remotely monitor patients. Their hypothesis was that personalized surveys via mobile messaging could be sensitive to ADHD-specific therapy effects.

“Technology opens the possibility of using measurements by mobile messaging to inform clinical care,” they wrote. “We know that ADHD symptoms respond rapidly to some forms of psychopharmacology as measured on well-validated rating scales. In clinical practice, individuals may find particular symptoms easier to recognize and report on than others.”

Investigators used the Weiss Functional Impairment Rating Scale (WFIRS) and the Adult ADHD Self Report Scale v1.1 (ASRS) to gauge patient-reported therapy effects.

Participants identified medication-sensitive items, and received such items as queries during selected time periods in the morning and evening. From this, investigators inferred “on” and “off” medication statuses for analyses.

In their outcome, the research observed that data confirmed self-reported ADHD symptom severity discriminated “on” versus “off” stimulant therapy status.

Investigators also noted sensitivity thresholds for symptom reporting, as well as reporting patters: within-day and between-day differences.

“Mobile monitoring of ADHD symptoms and functional impact is likely sensitive to changes in treatment status,” they concluded. “Future research may validate the clinical utility of using personalized self-reported mobile-messaged items in treatment optimization.”

The study, “Sensitivity of Electronic Patient Reported Outcome Measures to Medication Effects in Adult ADHD – A Pilot Study,” was presented at APSARD 2021.

Personalized, daily self-reporting for patients could influence future therapeutic strategies.