FDA Action Update, August 2021: Approvals, Submissions, and Designations

The FDA made several actions over the month of August 2021, including granting a number of approvals and accepting applications for novel therapies across a variety of neurologic and central nervous system (CNS) diseases.

With all the treatments that have progressed through the pipeline of clinical development, the NeurologyLive team has been hard at work covering all of those movements to make sure you are up to date on the latest news in neurology. To give you a chance to catch up on any of the headlines you may have missed over the course of the last month, we’ve compiled all the updates into one place. The coverage includes the latest FDA approvals, new designations, submissions and resubmissions, and clinical trial initiations.

Click the read more buttons for more detail and information about each update.

Diazepam Buccal Film NDA Resubmitted for Seizure Clusters

Aquestive Therapeutics originally received a complete response letter (CRL) for the agent in September 2020, but this new drug application (NDA) for diazepam (Libervant) buccal film for the management of seizure clusters was accepted with a prescription user drug fee act (PDUFA) target action date of December 23, 2021. After the company and the FDA completed a Type A meeting in late 2020, Aquestive provided additional statistical modeling and supportive analyses of the existing clinical data in the resubmission per the agency’s guidance.¹

LX1004 Gets Designation for CLN2 Batten Disease

The FDA granted a rare pediatric disease designation to LEXEO Therapeutics' LX1004 for the treatment of CLN2 Batten disease. The AAV-mediated therapy delivers CLN2 to the CNS and has completed assessment in a phase 1 clinical trial. That trial (NCT00151216) assessed the safety and was completed in June 2019, involving 10 patients with late infantile Batten disease. Results have shown that neurological decline was reduced in patients who received the gene therapy compared with controls, suggesting the strategy has the potential to delay disease progression. The company also announced that it has plans to advance the program into pivotal studies in 2022.²

APB-102 Fast-Tracked for SOD1 ALS

Apic Bio's APB-102 was given a fast track designation for the treatment of SOD1 amyotrophic lateral sclerosis (ALS), according to recent announcements. APB-102 is a recombinant AAVrh10 vector that expresses an anti-SOD1 artificial microRNA. Previously, it received orphan drug designation from the FDA and had its investigational new drug application cleared in April 2021. The agent is designed to expresses microRNA that binds to SOD1 mRNA in order to reduce the production of the mutant protein in patients with this form of the disease. Reducing mutant SOD1 protein levels is believed to improve survival and function of motor neurons and potentially provide a therapeutic benefit to people with SOD1-linked ALS.³

Avalglucosidase Alfa Approved for Late-Onset Pompe Disease

Sanofi announced that the FDA granted approval to avalglucosidase alfa-ngpt (Nexviazyme) for the treatment of late-onset Pompe disease in patients aged 1 year and older. The biologics license application for the long-term enzyme replacement therapy (ERT) was originally accepted for review in late 2020, after receiving breakthrough therapy and fast track designations. The monotherapy ERT is administered every 2 weeks, with a recommended dose based on body weight—20 mg/kg for patients weighing 30 kg or heavier, and 40 mg/kg for those patients under 30 kg—and is administered incrementally via intravenous (IV) infusion.⁴

OAV-101 Has Clinical Hold Lifted in SMA

Novartis' intrathecal (IT) gene therapy OAV-101 (onasemnogene abeparvovec) had its partial clinical hold lifted by the FDA last month, proceeding with the phase 1 STRONG trial (NCT03381729), after the company presented data from a comprehensive nonclinical toxicology study that addressed preclinical toxicity issues. Formerly known as AVXS-101, the agent is the IT version of Zolgensma, its IV gene therapy which received approval for the treatment of SMA in pediatric patients less than 2 years of age in March 2019. Shephard Mpofu, MD, senior vice president and chief medical officer, Novartis Gene Therapies, noted the company’s confidence in the agent as “a viable potential treatment path for older patients who often have ongoing unmet needs, and for whom a one-time treatment could be especially compelling," in a statement.”⁵

ALS001 Gets Designation for ALS

ALS001, a Coya Therapeutics product, was granted orphan drug designation for the treatment of ALS. The regulatory T cell (Treg) therapy is currently in an ongoing phase 2a trial (NCT04055623), with data anticipated by the end of summer 2021. The randomized, placebo-controlled trial will assess the tolerability of regulatory Tregs taken and expanded outside of the body, then reinserted IV with subcutaneous low-dose interleukin-2 (IL-2). The phase 1 open-label pilot study of the therapy found that during infusions of autologous expanded Tregs with concomitant subcutaneous injections of IL-2, Treg numbers increased, maximal inspiratory pressure (respiratory function) was stabilized, and notably, patients halted disease progression.⁶

Xywav Approved for Idiopathic Hypersomnia

Jazz Pharmaceuticals announced the approval of JZP-258 (Xywav) for the treatment of idiopathic hypersomnia. A combination agent of calcium, magnesium, potassium, and sodium oxybates, the oral solution received fast track designation from the FDA in September 2020, and in December 2020 was granted a rolling submission. Idiopathic hypersomnia is a debilitating neurologic sleep disorder characterized by chronic excessive daytime sleepiness (EDS). Most physicians in the space had turned to off-label use of wake-promoting therapies, typically used in patients with narcolepsy, to help address the sleepiness issues, marking the importance of JZP-258 as the first treatment approved for this indication.⁷

Pfizer COVID-19 Vaccine Approved for Ages 16 Years and Older

The Pfizer-BioNTech tandem’s COVID-19 vaccine BNT162b2 (Comirnaty) was approved a month after getting priority review designation to the biologics license application for the 2-dose inoculation.The indication is for those individuals aged 16 years and older, the same for which BNT162b2 was originally granted an emergency use authorization (EUA) in December 2020. Currently, those aged 12 to 15 years will still have access to the vaccine through the EUA, and the administration of a third dose is recommended for certain immunocompromised individuals.⁸

PoNS Device Gets Designation for Poststroke Deficits

Helius Medical Technologies announced last month that its Portable Neuromodulation Stimulator (PoNS) device received FDA breakthrough designation as a temporary treatment of dynamic gait and balance deficits due to symptoms of stroke. The PoNS system is intended to be used adjunct to a supervised therapeutic exercise program for patients 22 years of age and older. A nonsurgical device that includes a controller and mouthpiece, it delivers electrical stimulation to the surface of the tongue to provide treatment of gait deficit. It is currently indicated for us in the US as a short-term treatment for patients with multiple sclerosis (MS) who experience gait as part of their mild-to-moderate symptoms.⁹

Brivaracetam Approved for Partial-Onset Seizures

The FDA approved an expanded indication for brivaracetam (Briviact; UCB Pharma) CV tablets and oral solution, a treatment for pediatric patients with partial-onset seizures, with the indication also including an IV administered formulation for when oral administration is temporarily not feasible. This approval means the third-generation antiepileptic racetam derivative and a 4-n-propyl analogue of levetiracetam (Keppra; UCB Pharma) is now approved as both monotherapy or adjunctive therapy and is administered in tablets, oral solution, and IV dosage forms. Mike Davis, head, Neurology, UCB, said in a statement that the company used its epilepsy experience and “commitment to innovation to expand the indication for Briviact to reduce the number of partial-onset seizures these young and vulnerable patients are experiencing and provide their caregivers with an FDA-approved treatment."¹⁰

REFERENCES
1. Aquestive Therapeutics announces FDA acceptance of new drug application (NDA) resubmission for Libervant (diazepam) buccal film. News release. Aquestive Therapeutics. July 19, 2021. Accessed September 8, 2021. https://finance.yahoo.com/news/aquestive-therapeutics-announces-fda-acceptance-132900206.html
2. LEXEO Therapeutics receives rare pediatric disease designation and orphan drug designation for LX1004 for the treatment of CLN2 Batten disease. News release. LEXEO Therapeutics. July 28, 2021. Accessed September 8, 2021. https://finance.yahoo.com/news/lexeo-therapeutics-receives-rare-pediatric-123000141.html?guccounter=1
3. Apic Bio receives FDA fast track designation for APB-102 for the treatment of patients with SOD1 ALS. News release. Apic Bio. July 28, 2021. Accessed September 8, 2021. https://www.businesswire.com/news/home/20210728005193/en/Apic-Bio-Receives-FDA-Fast-Track-Designation-for-APB-102-for-the-Treatment-of-Patients-with-SOD1-ALS
4.FDA approves Nexviazyme® (avalglucosidase alfa-ngpt), an important new treatment option for late-onset Pompe disease. News release. Sanofi Genzyme. August 6, 2021. Accessed September 8, 2021. https://www.sanofi.com/en/media-room/press-releases/2021/2021-08-06-17-42-21-2276588
5. Novartis announces lift of partial clinical trial hold and plans to initiate a new, pivotal Phase 3 study of intrathecal OAV-101 in older patients with SMA. News release. Novartis. August 3, 2021. Accessed September 8, 2021. https://www.novartis.com/news/media-releases/novartis-announces-lift-partial-clinical-trial-hold-and-plans-initiate-new-pivotal-phase-3-study-intrathecal-oav-101-older-patients-sma
6. Coya Therapeutics receives orphan drug designation from the FDA for ALS001, an autologous treg cell therapy, for the treatment of ALS. News Release. Coya Therapeutics. July 7, 2021. Accessed September 8, 2021. https://www.globenewswire.com/news-release/2021/07/07/2258942/0/en/Coya-Therapeutics-Receives-Orphan-Drug-Designation-from-the-FDA-for-ALS001-an-Autologous-Treg-Cell-Therapy-for-the-Treatment-of-ALS.html
7. Jazz Pharmaceuticals Announces U.S. FDA Approval of Xywav® (calcium, magnesium, potassium, and sodium oxybates) Oral Solution for Idiopathic Hypersomnia in Adults. News release. Jazz Pharmaceuticals. August 12, 2021. Accessed September 8, 2021. https://www.prnewswire.com/news-releases/jazz-pharmaceuticals-announces-us-fda-approval-of-xywav-calcium-magnesium-potassium-and-sodium-oxybates-oral-solution-for-idiopathic-hypersomnia-in-adults-301354616.html
8. FDA Approves First COVID-19 Vaccine. News release. FDA. August 23, 2021. Accessed September 8, 2021. https://www.fda.gov/news-events/press-announcements/fda-approves-first-covid-19-vaccine
9. Helius Medical Technologies announces FDA breakthrough device designation for the treatment of dynamic gait and balance deficits following a stroke. News release. August 17, 2021. Accessed September 8, 2021. https://www.biospace.com/article/releases/helius-medical-technologies-inc-announces-fda-breakthrough-device-designation-for-the-treatment-of-dynamic-gait-and-balance-deficits-following-a-stroke/
10. UCB Announces Briviact (brivaracetam) CV now FDA-approved to treat partial-onset seizures in pediatric patients one month of age and older. News release. UCB Pharma. August 30, 2021. Accessed September 8, 2021. https://www.ucb-usa.com/stories-media/UCB-U-S-News/detail/article/ucb-announces-briviact-brivaracetam-cv-now-fda-approved-pediatric