6 FDA Decisions Expected Before 2024

After a relatively calm first 6 months in regulatory news from the US Food and Drug Administration (FDA), the latter half of 2023 is shaping up to be eventual—with dozens of New Drug Applications (NDA) and otherwise new drug indications on the docket.

Here’s a look into 6 PDUFA dates HCPLive has circled on its calendar for the last 6 months of 2023.

July 23: VP-102 (Verrica) for Molluscum Contagiosum

A drug-device combination product designed to deliver a controlled formulation of cantharidin 0.7%, VP-102 is on track to become the first drug approved to treat the viral-borne skin infection by the FDA.¹

Though Verrica’s pursuit of an FDA indication for molluscum contagiosum had been slowed by a Complete Response Letter (CRL) pertaining to a contract manufacturing organization not involved with VP-102’s manufacturing, the clinical development of the product itself has been a success. A pair of phase 2 clinical trials showed more patients treated with VP-102 reached complete clearance of their lesions and/or lesion count reductions versus a vehicle cream arm at 12 weeks (P <.0001).²

August 5: Zuranolone (Biogen & Sage) for Major Depressive Disorder & Postpartum Depression

The daily, oral neuroactive steroid and GABAA receptor agonist targets the primary mechanism of brain synapses, according to experts, and has been associated with 15-day improvement in each of Hamilton Depression Rating Scale (HDRS), Montgomery Asberg Depression Rating Scale (MADRS) and Clinical Global Impression of Improvement (CGIC) scores for patients with either major depressive disorder or postpartum depression.

“Depression treatment has really not advanced a lot in the last 20 years,” Anita Clayton, MD, chair of psychiatry and neurobehavioral sciences at the University of Virginia School of Medicine, told HCPLive last year. “A new mechanism of action is pretty exciting because there’s still many people who don’t respond to the standard-of-care treatments that we have currently.”³

In March this year, the FDA announced their intention to forego an advisory committee meeting regarding the New Drug Application (NDA) for zuranolone.⁴

August 19: Avacincaptad Pegol (Iveric Bio) for Geographic Atrophy

The complement 5 (C5) inhibitor could join exclusive company as just the second agent approved to treat the progressive form of vision loss, after pegcetacoplan (SYFOVRE) received the FDA nod in February this year.⁵ Phase 3 data published in late 2022 showed avacincaptad pegol reduced the mean growth rate of GA area by 14.3% over the first year of treatment versus sham—a difference of 0.056 mm (95% CI, 0.016 – 0.096; P = .0064).⁶

As the earliest drug class for this leading form of blindness develops, so may the clinical endpoints by which investigators validate agents like avacincaptad pegol. Veeral S. Sheth, MD, MBA, director of clinical research at the University of Retina and Macula Associates, emphasized the newness of complement inhibitors in a 2022 interview.

“This time point feels a lot like what it felt like 15 years ago when we were getting our first anti-VEGF therapies and saying to people for the first time, ‘Hey, we can actually alter the course of your disease in a meaningful way’,” Sheth said. ““I think we’re going to be looking at functional measures: reading speed, low luminance vision, you’re going to be looking at things like microperimetry—those are all things we’re going to be looking at.”⁷

October 17: Tenapanor (Ardelyx) for Chronic Kidney Disease

After receiving FDA approval for the treatment of irritable bowel syndrome with constipation (IBS-C) in September 2019,⁸ tenapanor’s progression toward decision for the treatment of serum phosphorus levels in adult patients with CKD on dialysis has been deliberate.

Ardelyx received a CRL from the FDA in July 2021, citing issues with the submitted efficacy data that would require an additional clinically relevant trial to assess tenapanor’s impact on serum phosphorus levels. In a statement accompanying the announcement, Arnold Silva, MD, PhD, director of Clinical Research at Boise Kidney and Hypertension Institute, argued for the agent’s real-world efficacy.

“I've closely followed the extensive clinical development of tenapanor, not only as an interested nephrologist, but also as a clinical investigator,” Silva said at the time. “I've seen the clinical benefits of tenapanor first-hand in my patients and I'm stunned that the FDA is not granting approval of this novel mechanism drug, despite extensive clinical data demonstrating its safety and efficacy."⁹

October 20: IDP-126 (Bausch) for Moderate to Severe Acne

The fixed-dose topical treatment combination of lindamycin phosphate 1.2%, benzoyl peroxide 3.1% and adapalene 0.15% has been associated with impressive data as recently as this spring. A post hoc analysis published in March showed the triple-combination cream was associated with a 10-fold greater success rate of treatment versus vehicle.¹⁰

Praise from would-be prescribers has been perhaps even more resounding than IDP-126’s supporting data. Hilary Baldwin, MD, medical director of the Acne Treatment & Research Center in New York, described the agent’s “excellent efficacy” in late-stage trials on its way to becoming the first acne drug with capability to treat each of the disease’s inflammation, bacteria and hyperkeratinization components in a single application.

“I think it’s going to blow me away,” Baldwin said. “I don’t see a scenario, except for maybe pregnancy, where I wouldn’t reach for this first.”¹¹

November 17: Vonoprazan (Phathom Pharmaceuticals) for Erosive Gastroesophageal Reflux Disease

After an FDA request for further sustainability data regarding the potassium-competitive acid blocker this January,¹² Phathom will seek indication to treat erosive GERD nearly 1 year later.

Leading up to its first potential FDA decision, vonoprazan was shown to completely resolve heartburn in ≤3 hours, with sustained relief for ≥24 hours, in approximately 7 of 10 treated patients with symptomatic nonerosie reflux disease.¹³

References

1. ^{Kunzmann K. FDA Accepts New VP-102 Application for Molluscum Contagiosum. HCPLive. Published February 28, 2023. https://www.hcplive.com/view/fda-accepts-new-vp-102-application-molluscum-contagiosum}
2. ^{Eichenfield LF, Siegfried E, Kwong P, et al. Pooled Results of Two Randomized Phase III Trials Evaluating VP-102, a Drug-Device Combination Product Containing Cantharidin 0.7% (w/v) for the Treatment of Molluscum Contagiosum. Am J Clin Dermatol. 2021;22(2):257-265. doi:10.1007/s40257-020-00570-8}
3. ^{Kunzmann K. Zuranolone Benefits Major Depression, Postpartum Depression in Clinical Program. HCPLive. Published May 22, 2022. https://www.hcplive.com/view/zuranalone-benefits-major-depression-postpartum-depression-clinical-program}
4. ^{Walter K. FDA Will Not Hold Advisory Meeting for MDD, PPD Drug Application. HCPLive. Published March 8, 2023. https://www.hcplive.com/view/fda-advisory-meeting-mdd-ppd-drug-application}
5. ^{Iapoce C. FDA Approves Pegcetacoplan Injection for Geographic Atrophy. HCPLive. Published February 17, 2023. https://www.hcplive.com/view/fda-approves-pegcetacoplan-injection-geographic-atrophy}
6. ^{Iapoce C. Avacincaptad Pegol for GA Meets Primary Efficacy Endpoint in GATHER2 Trial. HCPLive. Published October 1, 2022. https://www.hcplive.com/view/avacincaptad-pegol-meets-primary-efficacy-endpoint-gather2}
7. ^{Kunzmann K. What Avacincaptad Pegol Could Bring to Geographic Atrophy. HCPLive. Published February 10, 2023. https://www.hcplive.com/view/what-avacincaptad-pegol-could-bring-geographic-atrophywhat-avacincaptad-pegol-could-bring-geographic-atrophy}
8. ^{Walter K. FDA Approves Tenapanor to Treat Irritable Bowel Syndrome with Constipation. HCPLive. Published September 12, 2019. https://www.hcplive.com/view/fda-approves-tenapanor-treat-irritable-bowel-syndrome-constipation}
9. ^{Iapoce C. FDA Issues Complete Response Letter to Ardelyx for Tenapanor in Treatment of CKD. HCPLive. Published July 29, 2021. https://www.hcplive.com/view/fda-issues-complete-response-letter-ardelyx-tenapanor-treatment-ckd}
10. ^{Smith T. Triple-Combination Topical Treatment Effective for Acne in Pediatric Participants. HCPLive. Published March 29, 2023. https://www.hcplive.com/view/triple-combination-topical-treatment-effective-acne-pediatric-participants}
11. ^{Kunzmann K. Hilary Baldwin, MD: IDP-126 May Change Acne Management. HCPLive. Published June 24, 2023. https://www.hcplive.com/view/hilary-baldwin-idp-126-may-change-acne-management}
12. ^{Walter K. FDA will not Take Action on Potential Erosive Esophagitis. HCPLive. Published January 5, 2023. https://www.hcplive.com/view/fda-take-action-potential-erosive-esophagitis}
13. ^{Inman S. Vonoprazan Is Effective Against Heartburn in Symptomatic NERD. HCPLive. Published October 24, 2022. https://www.hcplive.com/view/vonoprazan-is-effective-against-heartburn-in-symptomatic-nerd}