FDA action alert: ARS Pharma, Appili, Ocuphire, and BrainStorm

Published: Sep 18, 2023

By Tristan Manalac


The FDA is gearing up for a busy second half of September with three target action dates and a highly-anticipated advisory committee meeting for an investigational amyotrophic lateral sclerosis (ALS) treatment.

ARS Pharma Anticipates Decision on Non-injectable Epinephrine Therapy

Following a three-month delay, the FDA on Sept. 19 is set to release its decision on ARS Pharmaceuticals’ New Drug Application for neffy, a nasal epinephrine spray being proposed to treat type 1 allergic reactions, including anaphylaxis.

The San Diego–based biotech is supporting its regulatory bid with four primary registrational studies, in which neffy elicited a pharmacokinetic profile that was within the range of approved injectable formulations of epinephrine. The FDA accepted the NDA in October 2022.

The majority of adverse events associated with neffy were mild, according to the announcement. There was no meaningful nasal irritation or pain associated with the investigational nasal spray.

In May 2023, the FDA’s Pulmonary-Allergy Drugs Advisory Committee voted in favor of neffy’s approval. Split 16–6, the panel of external experts deemed that ARS’s data demonstrated a favorable risk-benefit profile for neffy in adults. The turnout was slightly better in the pediatric setting, with the Committee voting 17–5 in favor of allowing neffy for children aged 18 years and younger. The FDA is not required to follow the advice of its advisory committees, though it often does.

In briefing documents published ahead of the May 2023 meeting, the regulator’s staffers flagged a lack of clinical data backing neffy. In particular, the reviewers stated that relying on pharmacokinetic and pharmacodynamic data—and the similarity of these profiles to approved epinephrine injections—could be an unreliable benchmark of efficacy and safety, especially as data for injections are scarce to begin with. Differences in the routes of administration may also affect these comparisons.

If approved, neffy would be the first non-injectable epinephrine therapy for allergies in the United States.

Appili Anticipates Decision on Liquid Reformulation of Metronidazole

Appili Therapeutics expects a verdict on its liquid oral reformulation of the antibiotic metronidazole, ATI-1501, on or before September 23.

The company has licensed ATI-1501 to Saptalis Pharmaceuticals and announced during an August 2023 earnings report that it expects to receive milestone payments in the coming quarters, based on Saptalis’ commercialization plans.

The FDA accepted the NDA for ATI-1501 in February 2023.

With over 10 million annual prescriptions in the U.S., metronidazole is a widely prescribed front-line oral antibiotic used commonly for parasitic and anaerobic bacterial infections, according to Appili’s website. Currently, metronidazole is only approved in tablet form, which poses medication barriers for very young patients and those who have difficulties swallowing, especially the elderly.

In these cases, the tablets are crushed and resuspended in food or drinks, which could result in dosing errors. Mixing metronidazole with food also does little to mask the drug’s bitter taste, which could turn patients off and lead to lower medication adherence.

Apilli’s reformulated liquid suspension of metronidazole not only masks its bitter taste, but also makes the medicine easier to administer, according to the company.

If approved, ATI-1501 could present a “convenient treatment option for those suffering devastating infections,” president and CEO Don Cilla said in a statement at the time of the NDA acceptance.

FDA to Decide on Ocuphire’s Eye Drops to Reverse Eye Dilation

The FDA is scheduled to decide next week on Ocuphire’s NDA proposing Nyxol (phentolamine ophthalmic solution 0.75%) for the treatment of pharmacologically-induced mydriasis, or pupil dilation. The regulator’s deadline is Sept. 28.

Using medication to induce eye dilation is a common clinical procedure, with around 100 million operations carried out in the U.S. annually. These are usually part of routine checkups, monitoring for eye diseases and preparation for eye surgeries.

Depending on patients’ eye color and other factors, artificial dilation can persist from six to 24 hours, during which time the eyes are more sensitive to light and have greater difficulty focusing on near objects. This can make it difficult for patients to read, work or drive. There are currently no approved agents to reverse mydriasis.

Ocuphire’s Nyxol is a stable and preservative-free ophthalmic formulation of phentolamine, which works by blocking α1 receptors on the iris dilator muscles. This, in turn, has the effect of modulating pupil size without affecting the ciliary muscles.

The Michigan–based biotech is supporting Nyxol’s NDA with data from its MIRA clinical development program, which enrolled more than 600 patients across four trials. Overall, the studies showed that Nyxol was significantly better than placebo at rapidly restoring baseline pupil diameter, which occurred from 60 to 90 minutes after administration.

The MIRA trials also demonstrated a favorable safety and tolerability profile for Nyxol in this indication. Pediatric data showed that Nyxol could also potentially be used to reverse dilation in children aged 3 years and above.

Aside from mydriasis, Ocuphire is also developing Nyxol for presbyopia and night vision disturbances.

BrainStorm’s NurOwn to Face Advisory Committee

On Sept. 27BrainStorm Cell Therapeutics’ investigational ALS therapy NurOwn (autologous bone marrow-derived mesenchymal stromal cells induced to secrete neurotrophic factors) will face the FDA’s Cellular, Tissue and Gene Therapies advisory committee.

The panel of external experts will evaluate the body of data supporting NurOwn and decide whether its benefit-risk profile is favorable and supports approval.

BrainStorm first tried seeking approval for NurOwn in 2021 but was turned back by the FDA, which stated that the company’s Phase III trial did not meet the evidence threshold required to support a Biologics License Application. The Israel- and New York–based biotech tried again in November 2022, but was met with a Refusal to File Letter, which flagged statistical and manufacturing concerns with the resubmission.

Following its second regulatory stumble, BrainStorm decided to leverage the FDA’s File Over Protest procedure to request an adcomm meeting—and to hopefully secure the fastest way to a regulatory verdict.

The ALS space has already seen the approval this year of Biogen and Ionis’ Qalsody (tofersen), which in May 2023 won accelerated approval for a specific type of ALS based on biomarker data. In particular, the pharma partners showed that Qalsody reduced levels of the neurofilament light chain and SOD1 protein, both of which could be indicative of clinical effect. A few months earlier, an advisory committee voted unanimously that these biomarkers could indeed be reasonable predictors of Qalsody’s therapeutic benefit.

In July 2023, a few months after securing the adcomm meeting, BrainStorm released Phase III data showing that NurOwn could also significantly lower neurodegeneration biomarkers, including neurofilament light chain.

Source: BioSpace