9 Highly Anticipated FDA Decisions in the Second Half of 2023

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Pictured: FDA Sign with blue sky background/Adobe Stock, Grandbrothers

The first half of 2023 saw some milestone FDA approvals, including a series of firsts in superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis, Rett Syndrome and Friedreich’s ataxia. The second half of this year could see at least four more—in Alzheimer’s disease, depression, sickle cell disease and advanced melanoma. BioSpace highlights nine FDA decisions to watch before the New Year. 

Eisai and Biogen’s Leqembi

Alzheimer’s disease

PDUFA date (for full approval): July 6

By far, the most highly anticipated FDA decision of the second half comes just six days in, when the regulator is expected to decide whether to grant traditional approval to Eisai and Biogen’s Leqembi (lecanemab).

Leqembi would be the first anti-amyloid antibody widely available to patients. While it won accelerated approval in January, the treatment’s uptake has been limited because the Centers for Medicare & Medicaid Services (CMS) will currently only cover the cost in the context of a clinical trial. A full approval—under which CMS has stated it will cover Leqembi, with some conditions—would open the floodgates, completely changing the Alzheimer’s treatment space with potentially significant economic impact.  

The FDA is widely expected to fully approve Leqembi. Earlier this month, it secured the unanimous backing of the regulator’s Peripheral and Central Nervous System Drugs Advisory Committee. FDA guidance documents were also positive, with agency staff signaling their belief that the Phase III CLARITY AD trial likely verified Leqembi’s clinical benefit.

If also approved in Europe and Japan, Leqembi is expected to earn its developers nearly $13 billion in sales over the next five years, according to research by Global Data Healthcare and reported by Pharmaceutical Technology.

Biogen and Sage’s Zuranolone

Major depressive disorder and postpartum depression

PDUFA date: August 5

Later this summer, Biogen and Sage Therapeutics will learn whether zuranolone will become the first fast-acting therapy for major depressive disorder (MDD) and postpartum depression (PPD). 

Zuranolone, a neuroactive steroid that works as a positive allosteric modulator of GABA-A receptors, has shown rapid and sustained improvement of depressive symptoms in clinical studies, according to Biogen. In the Phase III trial for PPD, the drug hit both primary and key secondary endpoints, demonstrating a statistically significant decrease in depressive symptoms compared to placebo. Zuranolone likewise hit its primary and key secondary endpoints in its Phase III MDD trial, eliciting a statistically significant reduction in depressive symptoms after three days when given with a standard-of-care antidepressant. 

Much of the excitement around zuranolone stems from its fast-acting nature. If approved, it would be the first 14-day treatment on the market for depression. Current treatments for these conditions are long-term, providing efficacy at 6–8 weeks, Sage Chief Business Officer Chris Benecchi told BioSpace in a previous interview.

The FDA accepted zuranolone’s New Drug Application (NDA) in February and granted it priority review. 

Roche’s Subcutaneous Tecentriq

Non-small cell lung cancer

PDFUA date: September 15

Roche is looking to bring a subcutaneous (SC) formulation of its blockbuster anti-PD-(L)1 therapy, Tecentriq to non-small cell lung cancer (NSCLC) patients.

Data from the Phase III IMscin001 study reported in August 2022 showed the SC formulation was non-inferior to intravenous Tecentriq in people with advanced NSCLC. Plus, the SC formulation of Tecentriq reduced the treatment time “to just minutes, compared with up to an hour for IV infusion,” according to Roche.

An approval for SC Tecentriq could mean more market exclusivity for Tecentriq, which could end in 2032, Evaluate Pharma reported.

Alnylam’s Patisiran and Ionis/AstraZeneca’s Eplontersen

AATR cardiomyopathy and ATTR polyneuropathy

PDUFA dates: October 8 and December 22

The transthyretin amyloidosis (ATTR) space could see two new FDA approvals in Q4 as competitors Alnylam and Ionis/AstraZeneca seek new indications. In October, the regulator will decide on a supplemental approval for Alnylam’s patisiran in cardiomyopathy associated with ATTR. Then in December, Ionis and Astra’s eplontersen in ATTR polyneuropathy (ATTRv-PN) will come under review.

Patisiran, an RNAi therapeutic, is already approved to treat ATTRv-PN, for which it is marketed as Onpattro. Approved in 2018, Onpattro was shown to improve polyneuropathy compared to placebo, with reversal of neuropathy impairment compared to baseline in the majority of patients. In ATTR with cardiomyopathy, patisiran demonstrated “favorable effects” on both functional capacity and quality of life compared to placebo after 12 months of follow-up.

Ionis and Astra hope to cut into this market share with eplontersen, an antisense medicine. In a Phase III trial, 47% of patients on the drug showed improvements in neuropathy. Both drugs improved quality of life metrics, according to the respective companies.

Iovance’s Lifileucel

Advanced melanoma

PDUFA date: November 25

Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) has been gaining momentum in the treatment of melanoma, but to date, no company has seen such a therapy across the regulatory finish line in this indication. That could change in November when the FDA will render its decision on Iovance Biotherapeutics’ lifileucel in advanced melanoma.

Iovance completed its rolling BLA submission to the FDA in March. Along with being potentially the first individualized, one-time cell therapy for patients with advanced melanoma, lifileucel would also be the first treatment option for patients whose unresectable or metastatic melanoma has progressed on or after prior anti-PD-1/L1 therapy and targeted therapy, where applicable.

In the C-144-01 trial, lifileucel elicited a 31% objective response rate at just over three years follow-up, with 42% of responses lasting for two years or longer, Iovance reported in November 2022.

BrainStorm’s NurOwn


PDUFA date: December 8

The second Friday in December could mark the end of a long road for BrainStorm Cell Therapeutics’ NurOwn.

The Israel- and New York–based biopharma first considered filing for approval of the investigational amyotrophic lateral sclerosis (ALS) therapy in 2021 but the FDA said the company’s Phase III trial didn’t meet the threshold of substantial evidence needed to support a BLA. The trial hit the primary treatment response endpoint, with 34.7% of patients achieving an improvement of 1.5 points per month on the ALS Functional Rating Scale – Revised (ALSFRS-R), but the placebo response of 27.7% exceeded those of others observed in contemporary ALS trials. 

In November 2022, the regulator again poured cold water on NurOwn’s bid, rejecting the BLA due to manufacturing and clinical and statistical concerns. BrainStorm leveraged the FDA’s File Over Protest procedure and the regulator granted NurOwn a public hearing in front of an advisory committee, which has been scheduled for Sept. 27.

BrainStorm has spent the past two years building its case—including with a corrected analysis of the pivotal data that showed treatment with NurOwn preserved more than two points on the ALSFRS-R after 28 weeks. 

If approved, NurOwn would be the second new ALS therapy in 2023 after Biogen and Ionis’s Qalsody got the FDA’s nod in April for SOD1-ALS.

CRISPR Therapeutics and Vertex’s exa-cel and bluebird bio’s lovo-cel

Sickle cell disease

PDUFA dates: December 8 and 20

Severe Sickle cell disease (SCD) patients could have two new treatment options by the end of this year.

First, on the same day the agency is set to decide on NurOwn, the FDA will weigh in on Vertex and CRISPR Therapeutics’ exagamglogene autotemcel (exa-cel).

If approved, exa-cel would be the first CRISPR gene editing product approved by the FDA for any indication. The BLAs for exa-cel in SCD and transfusion-dependent beta thalassemia (TDT) were the first filings for a CRISPR therapy to be accepted for FDA review. The action date for TDT is March 30, 2024.

Both SCD and TDT are caused by mutations in the beta-globin gene, which produces a protein critical to hemoglobin function. These mutations lead to abnormal hemoglobin, which leads to the anemia characteristic to both diseases.

Exa-cel is an autologous, ex vivo gene-edited therapy that uses the CRISPR-Cas9 system to edit a patient’s hematopoietic stem cells to produce high levels of fetal hemoglobin. In June 2022, the development partners presented data at the European Hematology Association Congress showing that exa-cel could prevent or substantially reduce transfusions in TDT and vaso-occlusive crises in SCD for more than 30 months. 

Hot on Vertex and CRISPR’s heels is bluebird bio, which is gunning for its third FDA-approved gene therapy for a rare disease. Like exa-cel, lovotibeglogene autotemcel (lovo-cel) is a one-time gene therapy. It is designed to add functional copies of a modified form of the beta-globin gene into a patient’s extracted hematopoietic stem cells. The registrational cohort for lovo-cel is based on 36 patients who were followed for approximately 32 months and two patients followed for 18 months. It also includes safety data from 50 patients.

The FDA is expected to make a decision on lovo-cel on December 20.

Heather McKenzie is a senior editor at BioSpace, focusing on neuroscience, oncology and gene therapy. You can reach her at heather.mckenzie@biospace.com. Follow her on LinkedIn and Twitter @chicat08.

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