The FDA’s calendar is relatively light in July, with only five major deadlines, including one for a PD-1 blocker and another for an opioid overdose drug.
Coming off of a busy month, July is looking relatively quiet for the FDA, with only five big target action dates and one pivotal advisory committee meeting. Read below for more.
Arcutis Proposes New Atopic Dermatitis Cream for Patients as Young as Six
By July 7, the FDA is expected to release its verdict on Arcutis Biotherapeutics’ supplemental New Drug Application (sNDA), seeking approval for a 0.15% formulation of roflumilast cream for the treatment of atopic dermatitis in patients as young as 6 years.
Roflumilast is a topical inhibitor of the phosphodiesterase 4 (PDE4) enzyme, which plays a role in increasing the production of pro-inflammatory mediators while dampening the body’s anti-inflammatory mechanisms.
A 0.3% formulation of roflumilast is approved under the brand name Zoryve for the treatment of psoriasis in patients 6 years and older. The FDA in December 2023 expanded roflumilast’s indication, allowing its use for seborrheic dermatitis in patients aged 9 and above.
Arcutis is backing roflumilast’s atopic dermatitis application with data from three Phase III programs, including INTEGUMENT-1 and INTEGUMENT-2, two identical parallel-group, double-blinded and vehicle-controlled studies. The 0.15% roflumilast cream aced these two studies, hitting four-week success rates of 32.0% and 28.9%, respectively.
In January 2024, Arcutis released additional pooled analysis from these two trials, demonstrating that 91.5% of patients treated with 0.15% roflumilast saw an improvement in the Eczema Area and Severity Index, measured at 4 weeks.
Roflumilast’s data package also included a Phase II dose-ranging study and a Phase I pharmacokinetic trial.
Orexo’s Opioid Overdose Drug Awaits FDA Verdict
Orexo AB is proposing its high-dose naloxone drug candidate OX124 as a nasal rescue treatment for opioid overdose. The FDA’s deadline for a decision is July 15.
Originally approved under the brand name Narcan, naloxone is a well-known treatment for opioid overdose. Currently available as an injectable and as a nasal spray, it works by competing with opioids for the same receptor sites, thereby undoing and dampening the drugs’ effects. Naloxone is effective at reversing the respiratory depression, hypotension and sedation often seen in patients who overdose on opioids.
Orexo’s investigational formulation of naloxone makes use of its “world-class drug delivery platform,” dubbed amorphOX, according to the company’s news release accompanying the acceptance of its NDA. Through amorphOX, Orexo delivers a powder formulation of naloxone that is rapidly absorbed, highly bioavailable and highly stable.
AmorphOX also makes naloxone more convenient and easier to use for patients, according to the company, making the product more robust to temperature changes. For instance, its efficacy is unaffected even if stored at freezing temperatures.
If approved, Orexo expects to kick off commercial activities in the second half of this year, with a broader retail launch scheduled in early 2025, CEO Nikolaj Sørensen said in a statement.
Phathom Pushes Voquezna into Heartburn in GERD
The FDA is reviewing Phathom Pharmaceuticals’ application to use its oral drug Voquezna (vonoprazan) for the treatment of heartburn associated with non-erosive gastroesophageal reflux disease (GERD). Its decision is due on July 19.
Afflicting around 38 million adults in the U.S., non-erosive GERD is the most common type of GERD and is characterized by reflux symptoms without mucosal erosions in the esophagus. Among its most common signs is episodic heartburn, which typically occurs at night. Patients with non-erosive GERD also suffer from regurgitation and chest pain and often have trouble swallowing.
Voquezna, a potassium-competitive acid blocker, works by suppressing acid secretion and acts with preference on parietal cells found in the stomach. This mechanism of action helped the drug win its first FDA approval in November 2023, allowing its use for the treatment of erosive GERD and the relief of heartburn in erosive GERD.
The NDA, which Phathom filed in September 2023, is backed by a randomized, placebo-controlled and double-blinded trial with 772 enrolled patients. Results showed that both the 10-mg and 20-mg doses of Voquezna aced the trial’s primary endpoint, resulting in a 45% and 44% mean percentage of heartburn-free days over the 4-week treatment period, respectively, whereas this figure was only 28% in placebo comparators.
During the study’s 20-week extension phase, the mean percentage of heartburn-free days in the 10-mg and 20-mg treatment groups increased to 62% and 63%, respectively.
Alpha Cognition Targets Second Oral Alzheimer’s Drug of the Past Decade
By July 27, the FDA is set to release its decision on Alpha Cognition’s NDA for ALPHA-1062, a next-generation acetylcholinesterase inhibitor being proposed for the treatment of mild-to-moderate Alzheimer’s disease.
Formulated as a delayed-release oral tablet, ALPHA-1062 is the prodrug of an already-approved acetylcholinesterase inhibitor, galantamine, according to Alpha Cognition. The candidate works through a similar pathway, boosting the activity of acetylcholine on nicotinic receptors and the cholinergic neurotransmission in the central nervous system, in turn inducing cognitive improvements.
Compared with galantamine, however, ALPHA-1062 promises a cleaner safety profile. It carries additional benzoyl ester moieties, which allow it to bypass acetylcholine receptors in the gastrointestinal nervous system, thereby avoiding the unwanted stimulation of local neurons and reducing side effects, according to Alpha Cognition’s website.
ALPHA-1062’s NDA, which the FDA accepted in December 2023, is supported by studies establishing the bioequivalence of the drug candidate to galantamine. If approved, ALPHA-1062 would be the second oral Alzheimer’s therapy in a decade, according to a February 2024 release from Alpha Cognition.
Xspray Tries Again for CML Therapy Dasynoc
In February 2024, the FDA accepted Xspray Pharma’s NDA resubmission for Dasynoc (dasatinib), being proposed for the treatment of chronic myeloid leukemia. The regulator’s verdict is due on July 31.
According to Xspray’s news release alongside the NDA’s acceptance, Dasynoc is an “optimized version” of Bristol Myers Squibb’s dasatinib, which the pharma sells under the brand name Sprycel. For instance, Dasynoc is unaffected by stomach pH and can be used together with omeprazole, as per Xspray’s website. Dasynoc also has a more consistent uptake profile and can be given at lower doses than Sprycel.
In July 2023, the FDA rejected Xspray’s initial bid to win approval for Dasynoc. At the time, the regulator accepted the proposed brand name and did not identify deficiencies with the application’s stability and clinical data. Instead, the FDA requested additional information regarding Dasynoc’s dosing in order to avoid confusion among doctors and patients. The regulator also asked for more information regarding a third-party manufacturer.
In a February 2024 news release, CEO Per Andersson said that despite the initial rejection, Xspray remains “on track” to launch Dasynoc on September 1, if approved.
FDA’s ODAC Convenes to Discuss AstraZeneca’s Imfinzi Regimen in NSCLC
On July 25, the FDA’s Oncologic Drugs Advisory Committee will meet to discuss AstraZeneca’s supplemental Biologics License Application for its antibody therapy Imfinzi (durvalumab) for the treatment of resectable non-small cell lung cancer (NSCLC).
The panel of external experts will evaluate AstraZeneca’s application for neoadjuvant treatment with Imfinzi and chemotherapy, followed by Imfinzi monotherapy after surgery. The advisory committee will also evaluate whether the pharma should be required to justify Imfinzi treatment before and after surgery.
Imfinzi is a monoclonal antibody designed to target and block the PD-L1 protein, in turn inhibiting its downstream signaling cascade. This mechanism hampers cancer cells’ ability to weaken and evade the immune system, while also boosting the body’s innate anti-cancer activity.
The FDA first approved Imfinzi in May 2017 for the treatment of advanced bladder cancer. The treatment has since been indicated for several other cancers, including unresectable stage III NSCLC, biliary tract cancer, pancreatic cancer and advanced or recurrent endometrial cancer.
In April 2023, AstraZeneca published data from the Phase III AEGEAN study showing that neoadjuvant Imfinzi with chemotherapy, followed by maintenance Imfinzi monotherapy, significantly improved event-free survival in patients with resectable early-stage NSCLC versus chemotherapy alone. The Imfinzi-based regimen also resulted in a significantly higher pathologic complete response.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
