Here is information on the latest US FDA approvals, the week of December 16 – December 22, 2023.
Test for Risk of Opioid Addiction
The FDA has approved the first test to assess if there is a risk of opioid use addiction in certain individuals. The test, called AvertD, has been developed by SOLVD Health. AvertD is intended to be used before the first use of oral opioid painkillers in patients who are being considered for a 4 to 30 days prescription for the treatment of acute pain, such as patients scheduled to undergo a planned surgical procedure. The test is for patients 18 years and older who have not previously used oral opioid painkillers and involves swabbing the cheek of a patient to collect a DNA sample. The sample is then used to determine if there is a combination of 15 genetic variants that may be associated with an elevated risk of developing opioid use disorder. Patients must consent to use of the test. According to the FDA, AvertD is not intended to be used in patients being treated for chronic pain. The test is being met with skepticism by some experts. There is a link to an article from CNN in the show notes if you’d like to delve further into this. The FDA granted the approval to AutoGenomics, which was acquired by SOLVD 2019.
https://www.cnn.com/2023/12/20/health/opioid-use-disorder-test-avertd/index.html
Filsuvez for Junctional Epidermolysis Bullosa
The FDA has granted approval to birch triterpenes topical gel (Filsuvez) for the treatment of Junctional Epidermolysis Bullosa (JEB) and Dystrophic Epidermolysis Bullosa (DEB), also known as ‘Butterfly Disease’. This marks the first FDA-approved therapy for the partial thickness wounds associated with JEB, a severe and rare form of EB that causes blistering from infancy. Available for individuals aged 6 months and older, the gel is a significant advancement in the management of this incapacitating skin disorder characterized by extreme skin fragility. The at-home application of this gel integrates into existing treatment routines. The approval, granted to Chiesi Global Rare Diseases, follows the May 2023 approval of B-VEC (Vyjuvek), a gene therapy for DEB, and further expands the treatment landscape.
https://resources.chiesiusa.com/Filsuvez/FILSUVEZ_PI.pdf
Budesonide for IgA Nephropathy
The FDA has granted full approval for budesonide delayed-release capsules (Tarpeyo) as a treatment to reduce the loss of kidney function in adults with IgA nephropathy (IgAN) who are at risk of disease progression. Budesonide is a corticosteroid and B-cell immunomodulator specifically designed to target pathogenic galactose-deficient IgA1 antibodies, which are implicated in the causation of IgAN. The medication is indicated for the treatment of proteinuria in adults with primary IgAN who are at risk for rapid progression of the disease, irrespective of the levels of proteinuria. This agent was initially authorized in 2021 under accelerated FDA approval. The full approval is based on findings from a multicenter, double-blind phase 3 NefIgArd clinical trial data. This marks the first time a treatment for IgAN has been fully approved by the FDA based on a measure of kidney function. Budesonide is also the only therapy currently approved by the FDA for primary IgAN that has been shown to potentially reduce the loss of kidney function, according to a written release from the FDA. The approval was granted to the Swedish company Calliditas Therapeutics.
https://www.tarpeyo.com/prescribinginformation.pdf
Eplontersen for hATTR Polyneuropathy
The FDA has approved eplontersen (Wainua) for the treatment of polyneuropathy associated with hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. hATTR-PN leads to rapid peripheral nerve damage and is often fatal within a decade if untreated. Eplontersen is a ligand-conjugated antisense oligonucleotide (LICA) designed to decrease the production of TTR protein in ATTR, a condition in which TTR is mutated. The approval is based on a 35-week interim analysis from the NEURO-TTRansform Phase III trial, published in the October 17th issue of JAMA. Additionally, eplontersen is under evaluation in the CARDIO-TTRansform Phase III trial for the potential treatment of ATTR cardiomyopathy, a systemic and fatal condition leading to progressive heart failure, often resulting in death within three to five years of onset. Eplontersen has been granted Orphan Drug Designation in the US and EU, with availability in the US expected in January 2024. Other agents already approved for hATTR-PN include patisiran, vutrisiran, and inotersen, all of which interfere with the production of TTR protein. Eplontersen is the only approved medicine that can be self-administered via an auto-injector. This week’s approval was granted to AstraZeneca and Ionis.
https://pubmed.ncbi.nlm.nih.gov/37768671/
https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217388s000lbl.pdf
NRX-101 for complicated UTI
The FDA has issued clearance for an Investigational New Drug (IND) application for NRX-101, which is a patented blend of D-cycloserine (DCS) and lurasidone. NRX-101 is being developed for the treatment of complicated urinary tract infections, which affect about 3 million Americans annually. According to a press release from the manufacturer NRx Pharmaceuticals, NRX-101comes at a time when “Americans are increasingly facing intravenous antibiotic therapy and even hospitalization and death from pathogens that were readily controlled a generation ago.” DCS is an NMDA-antagonist, which can lead to psychotomimetic effects such as hallucinations and confusion, and this led to its disuse as an antibiotic in the United States; however, the addition of lurasidone helps mitigate these effects. NRx Pharmaceuticals is also awaiting the FDA’s decision on their request for Qualified Infectious Disease Product (QIDP) designation for NRX-101. This designation pertains to the development of antibacterial and antifungal drug products that treat serious or life-threatening infections.
Gefapixant for chronic cough
The FDA last week issued a complete response letter, declining to approve Merck’s drug, gefapixant, for chronic cough, making this the second rejection of this agent in less than two years. According to the FDA, gefapixant, did not meet substantial evidence of effectiveness for treating refractory chronic cough (RCC) or unexplained chronic cough (UCC) in adults. Gefapixant is a selective antagonist of P2X3 receptors, with some activity against the P2X2/3 receptor subtype. P2X3 receptors are ATP-gated ion channels found on sensory C fibers of the vagus nerve in the airways. Currently, there are no approved treatments in the US for coughing bouts that don’t go away despite treatment of underlying conditions or have no identifiable cause.
V116 for Invasive Pneumococcal Disease
Despite the bad news regarding gefapixant, the FDA did accept for priority review a new Biologics License Application (BLA) for V116, Merck’s investigational 21-valent pneumococcal conjugate vaccine specifically designed to help prevent invasive pneumococcal disease and pneumococcal pneumonia in adults. The FDA grants priority review to medicines and vaccines that, if approved, would provide a significant improvement in the safety or effectiveness of the treatment or prevention of a serious condition. The application for V116 is based, in part, on data from STRIDE-3, a pivotal Phase 3 trial which evaluated the immunogenicity, tolerability and safety of V116 compared to PCV20 (pneumococcal 20-valent conjugate vaccine) in adults who had not previously received a pneumococcal vaccine. V116 is specifically designed to address Streptococcus pneumoniae serotypes predominantly responsible for adult pneumococcal disease, including eight unique serotypes, which account for approximately 30% of adult disease. The serotypes covered by V116 are responsible for approximately 83% of invasive pneumococcal disease in individuals 65 years of age and older. V116 is designed to be administered as a single dose. The FDA has set a target action date, of June 17, 2024.
Sotorasib in NSCLC
The KRAS G12C inhibitor Lumakras (sotorasib) received FDA’s accelerated approval in May 2021 for KRASG12C-mutated non-small cell lung cancer (NSCLC). Upcoming on December 24, (Sunday?) the FDA will decide whether or not to grant it full approval. The approval may not happen though because in October of this year, the FDA’s Oncologic Drugs Advisory Committee voted 10-2 against full approval of Lumakras in this indication, contending that the data from the confirmatory Phase III CodeBreaK 200 study could not reliably be interpreted. There is a link in the shownotes from OncLive that came out this week that provides a useful analysis of CodeBreak200 and the ODAC ruling, which just a recommendation (The FDA does not always follow the rulings of its advisory committtee). Sotorasib will still be available for clinical use regardless of the decision on Sunday.
https://www.onclive.com/view/codebreak-200-sotorasib-in-second-line-kras-g12c-mutated-nsclc
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