Levetiracetam

AAN, AES and SMFM Collaborate to Develop Updated Guidance MINNEAPOLIS, May 15, 2024 /PRNewswire/ -- A new guideline has been issued to help neurologists and other clinicians determine the best antiseizure medications for people with epilepsy who may become pregnant. The guideline is published in the May 15, 2024, online issue of Neurology®, the medical journal of the American Academy of Neurology (AAN), and was developed through a collaboration between the AAN, the American Epilepsy Society (AES) and the Society for Maternal-Fetal Medicine (SMFM). It was endorsed by the Child Neurology Society. The guideline partially updates two 2009 AAN and AES guidelines on the management of epilepsy during pregnancy, specifically regarding malformations at birth and the development of children born to people with epilepsy. "Most children born to people with epilepsy are healthy, but there is a small risk of pregnancy-related problems, partly due to seizures and partly due to the effects of antiseizure medications," said author Alison M. Pack, MD, MPH, of Columbia University in New York City, a Fellow of the American Academy of Neurology and a member of the American Epilepsy Society. "This guideline provides recommendations regarding the effects of antiseizure medications and folic acid supplementation on malformations at birth and the development of children during pregnancy so that doctors and people with epilepsy can determine which treatments may be best for them." The guideline recommendations are based on a review of all available evidence on the topic. Risks can include major congenital malformations, or birth defects, fetal growth issues and neurodevelopmental effects such as autism or lower IQ scores. The guideline states when treating people with epilepsy who may become pregnant, doctors should recommend medications and doses that optimize both seizure control and fetal development at the earliest possible opportunity before pregnancy. During pregnancy, it recommends minimizing the occurrence of tonic-clonic seizures, seizures with full body spasms, to minimize risks to the parent and fetus. It also says stopping medications during pregnancy may increase the frequency of seizures, which may harm the parent and fetus. For medications, the guideline recommends using lamotrigine, levetiracetam or oxcarbazepine when appropriate to minimize risk of major birth defects. It recommends avoiding valproic acid, phenobarbital and topiramate when possible. To reduce the risk of poor neurodevelopmental outcomes, including autism spectrum disorder and lower IQ scores, the guideline recommends clinicians avoid prescribing valproic acid, when possible, to people with epilepsy who may become pregnant. The guideline recommends that people with epilepsy who may become pregnant take at least 0.4 milligrams of folic acid daily before and during pregnancy to decrease the risk of neural tube defects and possibly improve neurodevelopmental outcomes. However, it notes further studies are needed to clarify the optimal dose and timing of folic acid supplementation. "People with epilepsy who may become pregnant want to ensure the best health of their child while still managing and minimizing their seizures," said Pack. "This is why it is important to discuss plans for pregnancy with your doctor before becoming pregnant and notify your doctor as soon as possible if you discover you are pregnant. Don't stop or change your medications. Talk with your doctor about any concerns you have about your medications." There are some medications that did not have enough evidence to be evaluated and need more research about their associated risk. The guideline was funded by the American Academy of Neurology. About the American Academy of Neurology The American Academy of Neurology is the world's largest association of neurologists and neuroscience professionals, with over 40,000 members. The AAN's mission is to enhance member career fulfillment and promote brain health for all. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer's disease, stroke, concussion, epilepsy, Parkinson's disease, multiple sclerosis, headache and migraine. For more information about the American Academy of Neurology, visit AAN.com or find us on Facebook, Twitter, Instagram, LinkedIn and YouTube. About the American Epilepsy Society Founded in 1936, the American Epilepsy Society is a medical and scientific society whose members are dedicated to advancing research and education for preventing, treating and curing epilepsy. AES is an inclusive global forum where professionals from academia, private practice, not-for-profit, government and industry can learn, share and grow to eradicate epilepsy and its consequences. About the Society for Maternal-Fetal Medicine (SMFM) The Society for Maternal-Fetal Medicine (SMFM), founded in 1977, is the medical professional society for maternal-fetal medicine subspecialists, who are obstetricians with additional training in high-risk pregnancies. SMFM represents more than 7,000 members who care for high-risk pregnant people and provides education, promotes research, and engages in advocacy to advance optimal and equitable perinatal outcomes for all people who desire and experience pregnancy. For more information, visit SMFM.org. SOURCE American Academy of Neurology

It’s just the latest grim reading for Addex Therapeutics, which has seen its lead programs knocked back in the clinic one after the other. Addex Therapeutics’ run of bad luck in the clinic shows no sign of ending, as a Janssen-licensed epilepsy drug has failed to reduce the occurrence of seizures in a phase 2 trial. ADX71149 is a positive allosteric modulator (PAM) of metabotropic glutamate receptor-2 that emerged from a 2004 collaboration between Addex and Janssen. The Johnson & Johnson unit had been running a phase 2 trial that included 110 evaluable patients whose focal onset seizures had not been adequately controlled by the approved epilepsy meds levetiracetam or brivaracetam. Participants received either a 50-mg or a 100-mg dose of ADX71149 twice daily on top of their standard dose of levetiracetam or brivaracetam and up to three other anti-seizure drugs. The midstage study failed to demonstrate a delay in the time it took for patients to reach their baseline seizure count, missing the trial’s primary endpoint, Addex revealed in an April 29 release. This is just the latest grim reading for Addex, which has seen its lead programs knocked back in the clinic one after the other. In 2022, the company revealed that a phase 2a clinical trial designed to spearhead the expansion of dipraglurant, a negative allosteric modulator of metabotropic glutamate receptor-5, into muscle spasm disorders had delivered “inconclusive” data. That left the Geneva-based biotech looking to the drug to prove its worth in a Parkinson’s disease study. But COVID-19 headwinds soon blew that study off course as well, leaving Addex at risk of being delisted from Nasdaq. The company’s CEO Tim Dyer would later explain to Fierce Biotech how persuading investors about the potential of the Janssen collaboration for ADX71149 helped steady the ship during this stormy moment. Now, even ADX71149’s fate appears to be up in the air. Chief Medical Officer Roger Mills, M.D., outlined in today’s early morning release how the biotech will “work with our partner to determine next steps for the ADX71149 program.” Dyer’s own comments stuck to his strategy of trying to focus investors’ attention on the pipeline’s remaining potential. “While this is disappointing news for us and our partner, Janssen, we remain focused on advancing the rest of our portfolio of allosteric modulator programs towards clinical studies,” the CEO said in the release. “In particular, we are making great progress in our GABAB PAM collaboration with Indivior, which is on track to select drug candidates for [investigational new drug]-enabling studies in June this year for substance use disorder and chronic cough programs.” Investors didn’t appear to be reassured, with Addex’s stock dropping 50% to $8 in premarket trading on the Nasdaq Capital Market on Monday morning from a Friday closing price of $16.10. Should the Janssen partnership come to end, the majority of the 109 million euros ($117 million) in potential development and regulatory milestone payments tied to the deal will forever remain out of reach for Addex. Still, the biotech received a welcome show of faith in its allosteric modulator tech earlier this month, when investment firm Perceptive Advisors paid Addex 5 million euros ($5.4 million) to take a portfolio of preclinical assets and spin them out into a new company called Neurosterix that launched with $63 million in initial funding. Addex still has control of dipraglurant, which is being evaluated for dyskinesia associated with Parkinson’s and post-stroke/traumatic brain injury recovery. The company is also deciding on a PAM of the GABAB receptor to take forward in chronic cough. Indivior licensed a GABAB PAM program from Addex in 2018 with the aim of taking a candidate into clinical trials for substance use disorder.