7 FDA Drug Decisions To Watch Through July 2022


From a new heart failure indication to a first-of-its-kind rare disease treatment, here's the most interesting PDUFA dates for the first half of the year.

7 FDA Drug Decisions To Watch For Through July 2022

The first half of 2022 is projected to be laden with opportunities for new drug approvals through the US Food and Drug Administration (FDA)—from added indications for proven drug classes, to first-of-its-kind clearances for investigative agents.

Here’s 7 Prescription Drug User Fee Act (PDUFA) decisions HCPLive will be paying close attention to through the first half of 2022.

Faricimab (Roche) for adults neovascular age-related macular degeneration (AMD) or diabetic macular edema (DME) - January

The injection therapy may become the first bispecific antibody approved to treat ophthalmic disease later this month—targeting the angiopoietin-2 (Ang-2) and vascular endothelial growth factor A (VEGF-A) pathways commonly associated retina disease progression.

The benefit of Faricimab was shown in pivotal data from the TENAYA and LUCERNE trials as well as the YOSEMITE and RHINE trials, for patients with nAMD and DME, respectively. Key endpoints included non-inferior improvement in patients’ best corrected visual acuity (BCVA) versus aflibercept (EYLEA).

Last November, TENAYA and LUCERNE study author Carl Regillo, MD, Director of Retina Service at Wills Eye Hospital, discussed the duration benefit of Faricimab’s treatment regimen relative to competitors including aflibercept.

“Having something that's more durable or longer acting is simply more forgiving, if you will,” Regillo told HCPLive. “Patients don't necessarily have to come in so frequently and so precisely.”

Faricimab will also be considered by the FDA for approval in treating adults with diabetic retinopathy (DR).

Intravenous (IV) tramadol (Avenue Therapeutics) for adults with acute pain who require an opioid - February

It has been a prolonged regulatory process for the controlled drug candidate; the FDA submitted a Complete Response Letter (CRL) regarding Avenue’s New Drug Application (NDA) in October 2020, pointing out safety risks identified in phase 3 data.

The FDA letter stated tramadol may not be safe for the intended population, as “opioid stacking” may occur in the event of analgesia onset during the treatment regimen. Opioid stacking is associated with increased risk of treatment-related adverse events, including misuse, respiratory distress, and unintended advancing sedation.

Avenue President and Chief Executive Officer Lucy Lu, MD, expressed belief the original NDA-supporting database “strongly supports the value” of IV tramadol as an alternative to IV Schedule II conventional opioids.

“We firmly stand behind the safety data in our NDA and the ultimate approvability of IV tramadol,” Lu said.

Last April, the FDA further delayed decision on the revamped IV tramadol NDA.

Gefapixant (Merck) for adults with refractory or unexplained chronic cough - March

It has been approximately 60 years since a new treatment been approved for chronic cough, a condition estimated to affect more than 10% of the population.

Merck’s selective P2X3 receptor antagonist is supported by phase 3 data from the COUGH-1 and COUGH-2 trials, a pair of multinational randomized studies assessing 45 mg and 15 mg gefapixant verus placebo.

Data presented at the European Respiratory Society (ERS) 2020 International Congress showed 45 mg gefapixent reduced 24-hour cough frequency by 18.45% (95% CI, -32.92 to -0.86; P = .041) versus placebo at 12 weeks in COUGH-1, then by 14.64% (95% CI, -26.07 to -1.43; P = .031) versus placebo at 24 weeks in COUGH-2.

Stuart Green, MD, Vice President of Late Stage Development at Merck, told HCPLive the difficulty within the market to identify and progress a new viable drug for chronic cough has been in actually understanding the mediating pathways associated with the condition.

“What we find is that there’s many different pathways, but some of these appear to more important in disease states than others,” he explained. “It’s because of advances in developing not only the understanding of the science, but drugs than can selectively target those pathways, that we’ve now been able to do the kind of studies that allow us to hopefully demonstrate benefit for people with this condition.”

Mavacamten (Bristol Myers Squibb) for Obstructive Hypertrophic Cardiomyopathy (oHCM) - April

BMS’ first-in-class cardiac myosin inhibitor is designed to decrease contractile function and improve VO2 in patients with the rare inherited disease.

Its benefit for the high-risk patient population was supported by phase 3 EXPLORER-HCM trial data, presented at the American College of Cardiology (ACC) 2021 Scientific Sessions. Patients with left ventricular outflow tract (LVOT) ≥50 mmHg and NYHA class II-III symptoms reported early and sustained improvements in questionnaire summary scores for cardiomyopathy when treated with mavacamten versus placebo over 30 weeks.

In fact, the mean Kansas City Cardiomyopathy Questionnaire (KCCQ) score difference of 9.1 (95% CI, 5.5 - 12.8) observed between treated and controlled patients was the largest for any medication assessed versus placebo through the metric.

Study author John Spertus, MD, of the University of Missouri-Kansas City, told HCPLive the mechanism of benefit associated with mavacamten is still becoming understood. He said the investigative drug may even effectively treat patients with heart failure with reduced ejection fraction (HFrEF).

“As we learn what’s causing these quality of life benefits, there may be other diseases that may also benefit from the drug,” Spertus said.

Empagliflozin (Jardiance; Bohering Ingelheim & Lilly) for adults with heart failure independent of left ventricular ejection fraction (LVEF) - May

Now regarding a drug already approved to treat patients with HFrEF: the SGLT-2 inhibitor therapy may become the first heart failure drug indicated for both reduced and preserved ejection fraction this year.

In EMPEROR-Preserved data presented at the European Society of Cardiology (ESC) 2021 Meeting, investigators reported a 21% relative risk reduction in composite outcome of cardiovascular death or hospitalization in adults with HF with LVEF >40% treated with empagliflozin.

Approximately half (47.9%) of treated patients reported a serious adverse event in the trial; 19.1% discontinued treatment due to such events.

On a recent episode of HCPLive podcast Heart Beats with Manesh Patel, MD, Duke University Assistant Professor of Medicine Marat Fudim, MD, broke down the EMPEROR-Preserved data and the growing impact of empagliflozin in treating heart failure.

“The SGLT-2 (inhibitors)…have emerged as this sort of weird miracle-like drug, because it has been found in back-to-back-to-back studies for now nearly half a decade to benefit cardiovascular outcomes all the way out to death…though this drug was initially developed as a diabetic drug,” Fudim explained.

Risperidone (Teva; MedinCell) for adults with schizophrenia - June

The extended-release injectable suspension therapy would be indicated monthly subcutaneous use once every 1 or 2 months in patients with schizophrenia.

It’s supported by findings from the phase 3 RISE and SHINE trial—the former assessing the injection therapy’s efficacy in delaying time to impending relapse versus placebo, and the latter assessing for long-term safety, tolerability and effectiveness through 56 weeks.

Dr. Hafrun Fridriksdottir, Executive Vice President of Teva’s Global R&D, described the trials as progress toward providing another option to at-need patients with schizophrenia.

“The advancements made in managing mental health conditions over the past decade have been shaped by offering patients new treatment options,” Fridriksdottir said. “Now, we are taking the same approach with long-acting treatments, using advanced science to improve disease outcomes for those living with schizophrenia.”

Roflumilast cream (Arcutis) for adults and adolescents with psoriasis - July

The once-daily topical formulation is a phosphodiesterase type 4 (PDE4) inhibitor that targets enzymes associated with overactive immune responses in patients with psoriasis.

Data from DERMIS-1 and DERMIS-2 showed roflumilast cream 0.3% was associated Investigator Global Assessment (IGA) success rates of 42.4% and 37.5%, respectively, while providing significant improvement in outcomes including Psoriasis Area Severity Index 75 (PASI 75) and patient-perceived symptoms per Psoriasis Symptoms Diary (PSD).

Douglas DiRuggiero, DMSc, PA-C, of the Skin Cancer and Cosmetic Dermatology Center, discussed roflumilast on a recent HCPLive Peers & Perspectives video series. He noted the greater “binding affinity” associated with the therapy compared to currently available PDE4 inhibitor crisaborole.

“We’ve got a lot of exciting things approaching the microbiome side of skin, approaching the intercellular blockade with JAK inhibitors and PDE4 inhibitors, things that will give us better options than just using the traditional topical steroids,” DiRuggiero said.

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