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FDA Action Update, April 2022: Extensions, Approvals, and Designations

Catch up on any of the neurology news headlines you may have missed over the course of the last month, compiled all into one place by the NeurologyLive® team.

Several FDA actions took place in April 2022, including an extension of an application for amyloidosis, the approval of imaging software and a new therapy for myasthenia gravis, and a breakthrough designation in multiple sclerosis.

With all the treatments that have progressed through the pipeline of clinical development, the NeurologyLive® team has been hard at work covering all the agency 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 and holds.

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

FDA Extends Review of Vutrisiran for ATTR Amyloidosis 3 Months

On April 4, the FDA extended the review period for vutrisiran 3 months. The Alnylam product’s new drug application (NDA) now has a target review date of July 14, 2022.1

Vutrisiran is an investigational subcutaneous RNA interface (RNAi) therapy in development for the treatment of transthyretin-mediated (ATTR) amyloidosis—both hereditary (hATTR) and wild-type. Importantly, there are no additional clinical data requests from the FDA for the NDA. In a statement, Alnylam announced that this extension on the review period has been offered to allow for the appraisal of new information related to a secondary packaging and labeling facility that had recently been inspected and needed classification for the FDA to complete its review, with no issues directly related to vutrisiran. Alnylam noted that it had identified a new facility for those processes and submitted an amendment to the NDA as a result.

The Alnylam product was granted fast track designation by the FDA for the treatment of polyneuropathy related to hATTR amyloidosis in April 2020, shortly after completing enrollment for its phase 3 HELIOS-A study (NCT03759379). The original data announcement displaying vutrisiran’s potential for hATTR amyloidosis from that trial were announced in January 2021.2 A year later, new 18-month data on the RNAi therapy were announced, demonstrating that it met the secondary end points measured in HELIOS-A.3

Pushkal Garg, MD, chief medical officer, and executive vice president, Development and Medical Affairs, Alnylam, said in a statement. that the company was “committed to working with the FDA and the new facility" and that they "are confident in our regulatory application and the body of data supporting the efficacy and safety of vutrisiran.”

FDA Approves Boston Scientific’s STIMVIEW XT Guided Imaging Software for DBS

On April 12, Boston Scientific’s STIMVIEW XT guided programming software, which allows clinicians to visualize in real-time both lead placement and stimulation modeling of brain anatomy for patients with Parkinson disease (PD) or essential tremor who undergo deep brain stimulation (DBS), was approved by the FDA.4

STIMVIEW XT is used in conjunction with the Vercise Genus DBS System, Boston Scientific’s patented product that received FDA approval in 2021. The Vercise system consists of a group of Bluetooth-enabled implantable pulse generators (IPGs) that power Cartesia Directional leads, designed to provide optimal symptom relief. It is the fourth generation of the DBS system since released in 2012, developed to build on the ongoing innovations being made in battery longevity, directionality, and stimulation capabilities.5 Using patient-specific 3D visualization, STIMVIEW XT empowers DBS programmers to optimize and deliver directional stimulation more efficiently.

Jill Ostrem, MD, medical director, Movement Disorders and Neuromodulation Center, University of California San Francisco, said in a statement at the time that "it’s exciting that clinicians will now have access to more sophisticated image guided programming tools supporting personalized DBS therapy. This advancement with STIMVIEW XT may also save time for the clinician as it could help avoid the trial and error in finding the precise location. Prolonged periods of time in adjusting stimulation settings can be stressful and tiring for patients."

FDA Grants Breakthrough Device Designation to Simoa Neurofilament Light Chain Test for Multiple Sclerosis

The FDA granted breakthrough device designation to Quanterix’s Simoa neurofilament light (NfL) chain test as a prognostic aid in assessing the risk of disease activity in patients with relapsing-remitting multiple sclerosis (MS) on April 22.6

Used to quantitatively measure NfL in human serum, plasma, and cerebrospinal fluid, the program is designed to enable accelerated development, assessment, and review processes, with the intention to provide patients with more timely access to breakthrough technologies or devices. Serum NfL is a biomarker of neuronal damage that is used not only to monitor disease activity and response to drugs, but to prognosticate disease course in patients with MS.

"There has been an ever-growing body of research with the Simoa NfL blood test supporting NfL as a reliable biomarker for MS disease activity prognosis and treatment response monitoring,” Mark S. Freedman, MD, MSc, HBSc, CSPQ, FANA, FAAN, FRCPC, professor of neurology, and director, Multiple Sclerosis Research, Ottowa Hospital, said in a statement.6 "The FDA’s grant of breakthrough device designation for this test has the potential to help the multiple sclerosis community further advance the optimal use of NfL measurements in both research and clinical practice aimed at more effective therapeutic management of the disease for the millions of patients suffering from the condition."

FDA Approves Ravulizumab for Adults With Generalized Myasthenia Gravis

On April 28, the FDA approved ravulizumab (Ultomiris; Alexion), a terminal compliment C5 inhibitor, for the treatment of patients with generalized myasthenia gravis (gMG) who are antiacetylcholine receptor (AChR) antibody positive. With the decision, ravulizumab becomes the first approved long-acting C5 complement inhibitor for this patient population.7

The approval was based on data from the phase 3 CHAMPION MG trial (NCT03920293), in which treatment with ravulizumab resulted in rapid and sustained improvement of symptoms in patients with gMG for up to 26 weeks. At the end of the treatment period, investigators observed statistically significant improvements on the primary end point of Myasthenia Gravis Activities of Daily Living (MG-ADL) total score compared with placebo (–3.1 vs –1.4; P <.001).8

Primary investigator James F. Howard, MD, distinguished professor of neuromuscular disease, University of North Carolina School of Medicine, said in a statement that, “despite recent advances, managing gMG is complex. Earlier intervention can preserve function and quality of life. This approval offers patients, including those with milder symptoms, a long-acting C5 inhibitor with early-onset and reliable efficacy."

Results from CHAMPION-MG were recently published in the New England Journal of Medicine Evidence. In this phase 3, double-blind study, patients on the study drug received body weight-based doses of 2400 to 3000 mg induction on day 1, then 3000 to 3600 mg every 8 weeks on day 15. Patients had AChR antibody-positive gMG and were allowed to be on stable-dose AChR and immunosuppressant therapy throughout the study.

Biogen Withdraws Aducanumab Application to EMA Shortly Following CMS National Coverage Determination

Although not FDA news, on April 20, the European Medicines Agency announced that Biogen Netherlands BV withdrew its application for marketing authorization of aducanumab (Aduhelm) for the treatment of Alzheimer disease in Europe.9

That announcement follows another recent announcement, this time from the Centers for Medicare & Medicaid Services (CMS), that the national coverage determination (NCD) was finalized for aducanumab (Aduhelm; Biogen) and future monoclonal antibodies directed against amyloid that are approved by the FDA for the treatment of Alzheimer disease (AD).10 The NCD does not waver much from the proposed decision that the agency announced earlier this year, in January 2022.11

The NCD decision was ultimately that Medicare will be able to cover agents in this class of medication if they receive traditional approval from the FDA under coverage with evidence development. As such, CMS noted that it will “provide enhanced access and coverage for people with Medicare [who are] participating in CMS-approved studies, such as a data collection through routine clinical practice or registries,” and that registry data may be used to observe reproduced results in real-world populations. Additionally, the agency noted that new therapies in this class that are approved may be available in additional care settings— outpatient departments or infusion centers, as examples—that people with Medicare utilize.

REFERENCES
1. Alnylam Announces 3-Month Extension of Review Period for New Drug Application for Vutrisiran. News release. Alnylam. April 4, 2022. Accessed May 3, 2022. https://www.businesswire.com/news/home/20220404005293/en/Alnylam-Announces-3-Month-Extension-of-Review-Period-for-New-Drug-Application-for-Vutrisiran
2. Alnylam reports positive topline results from HELIOS-A phase 3 study of vutrisiran in patients with hATTR amyloidosis with polyneuropathy. News release. Alnylam Pharmaceuticals. January 7, 2021. Accessed May 3, 2022. https://www.businesswire.com/news/home/20210107005224/en/Alnylam-Reports-Positive-Topline-Results-from-HELIOS-A-Phase-3-Study-of-Vutrisiran-in-Patients-with-hATTR-Amyloidosis-with-Polyneuropathy
3. Alnylam presents positive 18-month results from HELIOS-A phase 3 study of investigational vutrisiran in patients with hATTR amyloidosis with polyneuropathy. News release. Alnylam Pharmaceuticals. January 21, 2022. Accessed May 3, 2022. https://www.businesswire.com/news/home/20220121005075/en/Alnylam-Presents-Positive-18-Month-Results-from-HELIOS-A-Phase-3-Study-of-Investigational-Vutrisiran-in-Patients-with-hATTR-Amyloidosis-with-Polyneuropathy
4. Boston Scientific receives FDA approval for next-generation image-guided programming software for deep brain stimulation therapy. News release. Boston Scientific. April 12, 2022. Accessed May 3, 2022. https://news.bostonscientific.com/2022-04-12-Boston-Scientific-Receives-FDA-Approval-for-Next-Generation-Image-Guided-Programming-Software-for-Deep-Brain-Stimulation-Therapy
5. Boston Scientific Receives FDA Approval For The Vercise Genus™ Deep Brain Stimulation System. News release. Boston Scientific. January 22, 2021. Accessed May 3, 2022. https://news.bostonscientific.com/2021-01-22-Boston-Scientific-Receives-FDA-Approval-For-The-Vercise-Genus-TM-Deep-Brain-Stimulation-System
6. Quanterix granted breakthrough device designation from the FDA for NfL test for multiple sclerosis. News release. Quanterix. April 22, 2022. Accessed May 3, 2022. https://www.businesswire.com/news/home/20220421006165/en/Quanterix-Granted-Breakthrough-Device-Designation-from-U.S.-FDA-for-NfL-Test-for-Multiple-Sclerosis
7. Ultomiris (ravulizumab-cwvz) approved in the US for adults with generalized myasthenia gravis. News release. Alexion. April 28, 2022. Accessed May 3, 2022. https://www.businesswire.com/news/home/20220428005462/en/ULTOMIRIS%C2%AE-ravulizumab-cwvz-Approved-in-the-US-for-Adults-with-Generalized-Myasthenia-Gravis
8. Vu T, Meisel A, Mantegazza R, et al. Terminal complement inhibitor ravulizumab in generalized myasthenia gravis. NEJM Evidence. Published online April 26, 2022. doi:10.1056/EVIDoa2100066
9. Aduhelm: Withdrawal of the marketing authorization application. EMA website. April 20, 2022. Accessed May 3, 2022. https://www.ema.europa.eu/en/medicines/human/withdrawn-applications/aduhelm
10. CMS Finalizes Medicare Coverage Policy for Monoclonal Antibodies Directed Against Amyloid for the Treatment of Alzheimer’s Disease. News release. CMS. April 7, 2022. Accessed May 3, 2022. https://www.cms.gov/newsroom/press-releases/cms-finalizes-medicare-coverage-policy-monoclonal-antibodies-directed-against-amyloid-treatment
11. Jensen TS, Chin J, Baldwin J, et al. Monoclonal Antibodies Directed Against Amyloid for the Treatment of Alzheimer’s Disease. CMS website. January 11, 2022. Accessed May 3, 2022. https://www.cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=Y&ncaid=305&doctype=all&timeframe=30&sortBy=updated&bc=20