FDA Action Alert: Sarepta, Protalix, Otsuka/Lundbeck and More

FDA Action Alert logo/© Nicole Bean for BioSpace

The FDA is kicking off May with three target action dates and three advisory committee meetings, including one for a high-profile investigational gene therapy.

See below for the details. 

Eyenovia Eyes Approval for Pupil Dilation Product

On May 8, the FDA is set to release its verdict on Eyenovia’s MydCombi, a drug-device product that uses the company’s investigational drug delivery technology Optejet to administer its proprietary combination solution of tropicamide 1% and phenylephrine 2.5%.

In its NDA, which the FDA accepted in December 2022, Eyenovia proposed to use MydCombi to induce in-office pupil dilation.

Eyenovia backed MydCombi’s NDA with data from two Phase III clinical trials. MIST-1, a randomized, active-control, cross-over, superiority trial showed that compared with phenylephrine or tropicamide alone, MydCombi induced greater pupil dilation.

MIST-2 likewise found stronger pupil dilation after MydCombi treatment compared with placebo.

If approved, MydCombi would become the first commercial product to use Eyenovia’s Optejet platform, which uses high-precision piezo-print technologies to administer 6-8 μL of the drug, in line with the capacity of the eye’s tear film. This approach helps avoid overdosing and excessive exposure to other preservative chemicals in eye medicines, according to Eyenovia.

Protalix, Chiesi Take Second Shot in Fabry Disease

Israel biotech Protalix BioTherapeutics is awaiting the FDA’s decision for PRX-102 (pegunigalsidase alfa), an investigational enzyme replacement therapy intended to treat adult patients with Fabry disease. The target action date is May 9.

Protalix is co-developing PRX-102 with Chiesi Global Rare Diseases.

Fabry disease is an X-linked heritable disease caused by a dysfunctional lysosomal α-Galactosidase-A enzyme, which in turn leads to the build-up of the fatty substance globotriaosylceramide (Gb3) in blood vessels. Over time, Gb3 accumulation leads to pain, impaired sensations and organ failure, particularly of the kidneys and heart.

Expressed using plant cell cultures and chemically modified to achieve stability, PRX-102 is a recombinant version of the α-Galactosidase-A enzyme and is designed to restore the body’s ability to break down Gb3.

Protalix and Chiesi had previously submitted a BLA for PRX-102, which was rejected by the FDA in April 2021. A year later, in April 2022, the pharma partners posted positive Phase III data from the BALANCE study, which found that the candidate improved kidney function in Fabry disease patients.

The partners resubmitted the BLA in November 2022. It was accepted by the FDA the following month. On May 5, the European Commission (EC) granted PRX-102 marketing authorization for the treatment of adults with Fabry disease.

Otsuka/Lundbeck Seek First Agitation in Alzheimer’s Approval

On May 10, the FDA will make a decision on Otsuka and Lundbeck’s application to expand the label for Rexulti (brexpiprazole) tablets to include agitation associated with Alzheimer’s disease (AD).

The verdict will follow a 9–1 vote by the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee in favor of Rexulti. The committee found that its efficacy and the unmet medical need in AD-associated agitation outweigh the drug’s potential safety risks.

If it passes the FDA’s rigor, Rexulti would become the first approved medication for agitation in AD in the U.S.

Rexulti is an atypical antipsychotic drug that was approved in 2015 as an adjunctive therapy for major depressive disorder and again in January 2022 for the treatment of schizophrenia in patients aged 13 years and older. This drug class was given a boxed warning in 2005 for increased risk of death among elderly patients.

During the adcomm, the panel of external experts examined data from three Phase III studies and weighed Rexulti’s benefits—a marked improvement in agitation, as measured by validated tools­—against the known mortality risks associated with the drug.

HRA Pharma Aims to Make Birth Control Pill OTC

From May 9 to May 10, the FDA’s Nonprescription Drugs Advisory Committee will hold a joint meeting with the Obstetrics, Reproductive and Urologic Drugs Advisory Committee to discuss HRA Pharma’s supplemental NDA (sNDA) for its Opill (norgestrel) birth control tablet.

The company is proposing to flip Opill from a prescription medicine to an over-the-counter drug, citing the need for greater access to birth control medication in the U.S., as well as the drug’s efficacy and safety, as proven by nearly 50 years’ worth of market use and scientific evidence.

If approved, Opill would become the first daily birth control pill available without a prescription.

Opill is a progestin-only, non-estrogen birth control pill consisting of 0.075-mg of norgestrel. The drug was first approved in 1973 and has since been used to avoid pregnancies in “millions of women in the U.S.,” according to the company’s press release announcing its sNDA application.

Several groups are backing HRA Pharma’s bid to remove the prescription barrier for Opill, including the American Academy of Family Physicians, American Medical Association and American College of Obstetricians and Gynecologists.

Adcomm to Discuss ARS Pharma’s Epinephrine Nasal Spray

On May 11, the Pulmonary-Allergy Drugs Advisory Committee will convene to deliberate on ARS Pharmaceuticals’ NDA for its epinephrine nasal spray, neffy, which the company is proposing for the emergency treatment of type 1 allergic reactions, including anaphylaxis.

ARS supported neffy’s application—which the FDA accepted in October 2022—with findings from four primary registrational studies, which together show neffy consistently met its primary efficacy metrics, as recommended by regulators. Data also demonstrate that neffy’s pharmacokinetic profile was within the range of other approved epinephrine injections.

In terms of safety, neffy induced adverse events that were mostly mild and did not cause nasal irritation or pain.

If approved, neffy would become the first non-injectable epinephrine product for allergic reactions in the U.S.

Sarepta’s DMD Gene Therapy Faces FDA Adcomm

In a much-anticipated meeting on May 12, the FDA’s Cellular, Tissue and Gene Therapies Advisory Committee will convene to discuss Sarepta’s investigational gene therapy, delandistrogene moxeparvovec, for Duchenne muscular dystrophy (DMD).

DMD is a rare neuromuscular disorder caused by mutations in the dystrophin gene, leading to muscle weakness and developmental delays. Delandistrogene moxeparvovec works by delivering a functional copy of the dystrophin gene to muscle tissues. If approved, it would be the first gene therapy for DMD.

Sarepta is backing delandistrogene moxeparvovec’s BLA—which the FDA accepted in November 2022—with data from three studies: RP-9001-101, SRP-9001-102 and SRP-9001-103. All in all, data from more than 80 patients showed that Sarepta’s gene therapy candidate can increase dystrophin expression and improve functional outcomes, though results were mixed.

The FDA previously indicated that it did not intend to hold an advisory committee meeting for the BLA, Doug Ingram, president and CEO of Sarepta, said during the company’s full-year 2022 financial report. 

However, the regulator changed course and announced in March 2023 that it would convene its external experts to discuss the gene therapy. The decision to hold an adcomm meeting was not due to new data regarding delandistrogene moxeparvovec and the company does not expect it to lead to delays in the target action date, which is May 29, 2023.

Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.