Latest news with #neurofibromatosis
Medscape
23-05-2025
- Health
- Medscape
Irish Drug Ezmekly Gets EU Nod for Plexiform Neurofibromas
At its May 2025 meeting, the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) gave a conditional marketing authorization for mirdametinib (Ezmekly, Springworks Therapeutics Ireland Limited) for the treatment of plexiform neurofibromas (PN) in adults and children from 2 years of age with neurofibromatosis type 1 (NF1). Plexiform neurofibroma is a genetic condition that manifests with irregular, thick, ill-defined tumors of the peripheral nerve sheaths. Most are benign, but some can change into cancerous tissue. The CHMP grants conditional marketing authorization to a medicinal product when it can fulfil an unmet medical need and the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required. It was based on the findings of the ReNeu trial: an open-label, multicenter, pivotal, phase IIb trial of mirdametinib in adults aged 18 and older (n = 58) and children aged 2-17 years (n = 56), with NF1-PN causing significant morbidities. Patients received mirdametinib capsules or tablets for oral suspension in 3 weeks on/1 week off, 28-day cycles. Twenty-four of 58 adults (41%) and 29 of 56 children (52%) had a blinded independent central review confirmed objective response during the 24-cycle treatment phase. In addition, two adults and one child had confirmed responses during long-term follow-up. The median target plexiform neurofibroma volumetric best response was -41% in adults and -42% in children. Both cohorts reported significant and clinically meaningful improvement in patient- or parent proxy-reported outcome measures of worst tumor pain severity, pain interference, and health-related quality of life that began early and were sustained during treatment. The researchers said that mirdametinib treatment was well-tolerated in adults and children with the most commonly reported treatment-related adverse events being dermatitis acneiform, diarrhea, and nausea in adults and dermatitis acneiform, diarrhea, and paronychia in children. Treatment Provides Durable Responses The active substance of Ezmekly, mirdametinib, is a selective, non-competitive mitogen-activated protein kinase 1 and 2 (MEK 1/2) inhibitor. By inhibiting MEK, mirdametinib blocks the proliferation and survival of tumor cells in which the rapidly accelerated fibrosarcoma‑MEK-extracellular related kinase pathway is activated. In granting the authorization, the CHMP said that the benefits of Ezmekly were its ability to provide durable responses: reduction of the volume of PN in adults and children from 2 years of age with NF1-associated symptomatic, inoperable PN. Ezmekly will be available as 1 mg and 2 mg hard capsules and 1 mg dispersible tablets as monotherapy for the treatment of symptomatic, inoperable PN in pediatric and adult patients with NF1 aged 2 years and older. Ezmekly was designated as an orphan medicine during its development for use against a rare, life-threatening, or chronically debilitating condition or, for economic reasons, would have been unlikely to have been developed without incentives. The EMA said that it would now review the information available to-date to determine if the orphan designation can be maintained.
Globe and Mail
14-05-2025
- Business
- Globe and Mail
Pasithea Therapeutics Announces Initiation of Phase 1/1B Study of PAS-004 in Adult NF1 Patients and Activation of First Clinical Trial Site
-- First patient expected to be dosed during Q2 2025 -- -- Trial will evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy in both plexiform neurofibromas and cutaneous neurofibromas -- -- Starting dose of 4mg tablet QD (once daily) -- -- First trial site in Australia. Four additional sites planned for Australia, South Korea, and U.S. – -- Australian R&D Tax Incentive refund of up to 48.5% of eligible study-related costs expected -- MIAMI, May 14, 2025 (GLOBE NEWSWIRE) -- Pasithea Therapeutics Corp. (NASDAQ: KTTA) ('Pasithea' or the 'Company'), a clinical-stage biotechnology company developing PAS-004, a next-generation macrocyclic MEK inhibitor today announced initiation of its Phase 1/1b open label study to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of PAS-004, in adult participants with neurofibromatosis type 1 (NF1) with symptomatic and inoperable, incompletely resected, or recurrent plexiform neurofibromas. The study will also assess preliminary anti-tumor activity and help determine a recommended dose for subsequent Phase 2 trials. Exploratory objectives include assessing the effects of PAS-004 on cutaneous neurofibromas. The first active clinical trial site is the Royal North Shore Hospital in Sydney, Australia, which is expected to begin patient enrollment in Q2 2025. Additional clinical trial sites in Australia, South Korea, and the United States are expected to be opened in the coming months. Pasithea has selected Novotech (Australia) Pty Limited as its clinical research organization (CRO) for this trial. The Company is conducting the study through its wholly owned subsidiary in Australia, Pasithea MacroMEK Pty Ltd, and anticipates eligibility for an Australian R&D Tax Incentive with a cash refund of up to 48.5% of the amount spent annually on eligible R&D activities (trial costs) in Australia. Dr. Rebecca Brown, M.D., Ph.D. a member of Pasithea's Scientific Advisory Board and Associate Professor of Neuro Oncology at The University of Alabama at Birmingham commented, 'I am pleased to have collaborated with the Pasithea team on the design of a comprehensive dose exploration and expansion study to assess the safety and tolerability of PAS-004 in adult NF1 patients. In addition to testing the effects of PAS-004 on plexiform neurofibromas, exploratory endpoints will also examine the effects of PAS-004 on cutaneous neurofibromas. The safety profile observed to date in advanced cancer patients is encouraging, and I look forward to seeing that profile translate to the NF1 population.' Dr. Brown added, 'One of the biggest challenges in treating plexiform neurofibromas associated with NF1 is ensuring that patients remain on MEK inhibitor therapy over the long-term. Real-world data shows that a significant proportion of NF1 patients discontinue treatment due to poor tolerability, including high rates of rash and gastrointestinal side effects. PAS-004 is also given as a once daily dose that offers a more convenient regimen than current FDA-approved therapies that are dosed twice a day and which could improve patient compliance.' Dr. Tiago Reis Marques, Pasithea's Chief Executive Officer, said, 'Following our recent financing, including the exercise of certain warrants, Pasithea is now funded to produce initial interim patient data in NF1. The initiation of this clinical trial in NF1, the initial indication we seek FDA marketing approval for, marks an important milestone for Pasithea and for patients living with NF1-related plexiform neurofibromas. Activating our first clinical trial site underscores our commitment to advancing PAS-004 as a potential best-in-class next-generation MEK inhibitor. We are encouraged by the safety and clinical data observed to date in oncology patients and are optimistic that PAS-004's tolerability profile will extend to the NF1 population. Importantly, our existing cancer data has enabled us to begin the NF1 trial at a higher dose than originally contemplated. In addition, we anticipate meaningful cash rebates of eligible trial costs through the Australian R&D Tax Incentive, further enhancing the efficiency of this program.' About the Phase 1/1b Clinical Trial in Adult NF1 Patients The primary objective of the Phase 1/1b study (NCT06961565) is to evaluate the safety and tolerability of PAS-004 when administered for one 28-day treatment cycle in adult NF1 participants with at least one and up to two additional target plexiform neurofibromas (PNs) that are symptomatic and inoperable, incompletely resected, or recurrent. Secondary objectives are (i) to identify the recommended Part B dose ('RPBD') or Maximum Tolerated Dose (MTD) of PAS-004, (ii) to characterize the PK and PD profile of PAS-004, (iii) to evaluate the preliminary efficacy of PAS-004 on target PN volume, (iv) to evaluate the preliminary efficacy of PAS-004 on the size, appearance, and associated symptoms of cutaneous neurofibromas (CNs), and (v) to evaluate the impact of PAS-004 on quality of life ('QOL') and any physical symptoms attributed to the target PN. Experimental objectives are (i) to evaluate the impact of PAS-004 on QOL and any physical symptoms attributed to CNs, (ii) to evaluate the impact of PAS-004 on pain and function attributed to PNs, and (iii) to investigate PAS-004 effects on CN tumor cellular and molecular biology. The trial will be conducted in two parts. In Part A, following a screening period of up to 28 days, up to 24 eligible participants will be enrolled sequentially to receive one of four planned dose levels of PAS-004 tablets (4mg, 8mg, 12 mg, 18mg) in a modified 3+3 design. Part A will identify the recommended RPBD. During Part B, up to 24 eligible participants will be enrolled in parallel to receive one of two planned dose levels of PAS-004 tablets. Participants will be dosed at the RPBD level and at a dose level below the RPBD for up to six continuous 28-day treatment cycles. Part B will identify the recommended phase 2 dose (RP2D). The study is planned to be conducted at five clinical trial sites in Australia, South Korea and the U.S. To learn more about the PAS-004 clinical trial in adults with NF1-associated plexiform neurofibromas, please visit About Pasithea Therapeutics Corp. Pasithea is a clinical-stage biotechnology company focused on the discovery, research and development of innovative treatments for central nervous system (CNS) disorders, RASopathies and MAPK pathway driven tumors. Forward-Looking Statements This press release contains statements that constitute 'forward-looking statements' made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include statements regarding the Company's ongoing Phase 1 clinical trial of PAS-004 in advanced cancer patients, the Company's Phase 1/1b clinical trial of PAS-004 in adult patients with NF1-associated plexiform neurofibromas, and the safety, tolerability, pharmacokinetic (PK), pharmacodynamics (PD) and preliminary efficacy of PAS-004, as well as all other statements, other than statements of historical fact, regarding the Company's current views and assumptions with respect to future events regarding its business, as well as other statements with respect to the Company's plans, assumptions, expectations, beliefs and objectives, the success of the Company's current and future business strategies, product development, pre-clinical studies, clinical studies, clinical and regulatory timelines, market opportunity, competitive position, business strategies, potential growth opportunities and other statements that are predictive in nature. Forward-looking statements are subject to numerous conditions, many of which are beyond the control of the Company. While the Company believes these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements, which are based on information available to the Company on the date of this release. These forward-looking statements are based upon current estimates and assumptions and are subject to various risks and uncertainties, including risks that future clinical trial results may not match results observed to date, may be negative or ambiguous, or may not reach the level of statistical significance required for regulatory approval, as well as other factors set forth in the Company's most recent Annual Report on Form 10-K, Quarterly Report on Form 10-Q and other filings made with the U.S. Securities and Exchange Commission (SEC). Thus, actual results could be materially different. The Company undertakes no obligation to update these statements whether as a result of new information, future events or otherwise, after the date of this release, except as required by law. Pasithea Therapeutics Contact
Health Line
11-05-2025
- Health
- Health Line
Mom, Daughter Diagnosed With NF1-PN: What to Know About the Rare Disease
A mother and daughter share the same rare genetic disease that causes tumor growth throughout the body. After living with neurofibromatosis type 1 with plexiform neurofibromas (NF1-PN) for four years, daughter Samatha Pearson was accepted into a clinical trial that changed her life. The mother-daughter duo shares their journey of managing the condition and advocating for others living with the rare disorder. In July 2015, Samantha Pearson was at summer camp playing a running game in the gym when her knee buckled, and she collapsed. 'The pain started immediately,' she told Healthline. When she told her parents about the pain, they decided to wait and see if it would subside on its own. However, after a few days of constant pain, they took her to the doctor. 'After doing an X-ray of my knee cap, he showed mom the tumor in my femur and knee, and he said to go see an orthopedic surgeon,' said Samantha. A couple of days later, at the orthopedic surgeon's office, an X-ray of Samantha's waist down revealed 27 tumors. The doctor informed Samantha and her mom, Michelle, that she most likely had neurofibromatosis type 1 (NF1) with plexiform neurofibromas (PN), a chronic disease in which tumors grow along nerves and can cause severe pain, mobility issues, and disfigurement. 'He handed me a note with the condition written on it and told me to call Shriners Children in Salt Lake City because there was no one in Las Vegas who could treat her. I was terrified,' Michelle told Healthline. A rare genetic disease After waiting for several months, Samantha was able to get an appointment at Shriners Children's Hospital in October 2015. 'The doctor took one look at Samantha and said, 'You have neurofibromas' and he looked at me and said, 'She got it from you,'' said Michelle. While NF1 is a genetic condition, as many as half of those diagnosed with NF1 might not have a family member with the condition, said Phioanh Leia Nghiemphu, MD, professor of clinical neurology at the University of California, Los Angeles, and clinical director of the UCLA Neurofibromatosis Program. 'Within one family, the manifestations of NF1 can also be different, so even if a family has many members with NF1, not all of them will have NF1-PN,' she told Healthline. Like the Pearsons, people with NF1 might have PN developed since birth, but the PN might not be diagnosed until their late adolescence or adult age, Nghiemphu added. Based on visual characteristics of the condition, including neurofibromas and freckling, the doctor determined that both Samantha and her mother have the same condition. Michelle had experienced partial deafness in her left ear for about a decade, which she learned was due to a tumor near her ear. 'It was a shock. I had never heard the word neurofibromas before,' said Michelle. 'I had no idea I had this. When the doctor told us about the visual characteristics, I asked my parents if it runs in the family and I checked out my two boys to see they had any symptoms.' Her sons showed no signs and her parents knew of no one else in the family with the condition. Michelle was relieved that her sons didn't have the condition and that she didn't experience debilitation or pain from it. However, it was difficult to witness Samantha's suffering, she said. 'Because [the tumors] grow on nerves and can grow very large, they can cause disfiguration, pain, difficulty using various body organs because of compression, or numbness and paralysis,' said Nghiemphu. Removing tumors by surgery can be painful, too, yet if they are not removed, they have a rare risk of developing into cancer called malignant peripheral nerve sheath tumor (MPNST), which is rare. But in most cases, NF1 is not a deadly disease. Most people with the condition have an average life expectancy. A life-changing clinical trial Because Shriners does not provide emergent care, Samantha was referred to Primary Children's Hospital in Salt Lake City to have the tumor in her left femur removed. However, the doctor who was recommended to Michelle through a parents' support group had a three-year waiting list. 'I didn't care that he had a three-year waiting list. I wasn't going to leave until Samantha saw him,' said Michelle. 'I was unruly, outspoken, and unconventional cause I'll do anything for my kid. I had no interest in keeping quiet. My daughter was not well.' Her advocacy resulted in Samantha receiving care from the doctor, who suggested that Samantha participate in a clinical trial. After not qualifying for several trials, in 2019, she finally qualified for the Phase 2b ReNeu trial, which studied the medication Gomekli (mirdametinib). Samantha took the first dose of medication in December 2020. 'The beginning of the trial was rough. I got a bad, painful acne rash, nausea, and vomiting was the worst part. I had no appetite, and I'd try to eat something and then immediately throw up,' said Samantha. After about six months of participating in the trial, she was ready to give up until she received good news. 'My mom and dad were moving my brother to college and big things for the boys always turn into something about me and so I wanted to be respectful, so I asked mom if she had two minutes to walk away and hear good news,' said Samantha. She shared that the doctors informed her that her tumor had shrunk by 82%. By the end of the trial, she had 90% shrinkage by volume and her pain was significantly reduced. 'Before the trial… even putting on a t-shirt or bra would hurt it. I'm a very physical touch person and love hugs; hugs would hurt. Coughing too hard would hurt, sneezing would hurt,' said Samantha. The Food and Drug Administration (FDA) approved Gomekli in February 2025 for adults and children with NF1-PN. The approval was based on the trial Samatha participated in. 'A few years ago, surgery was the only option, which can lead to many complications, and up to approximately 85% of plexiform neurofibromas cannot be completely removed through surgery,' said Nghiemphu. In addition to Gomekli, there is one other FDA-approved medication for the treatment of PN in pediatric patients with symptomatic, inoperable NF1-PN. However, it is not approved for adults. 'It is very recent that we finally have medical treatments for NF1-PN, but they are not perfect and do not work for everyone, and we hope that we can continue with research programs that help patients with these rare conditions so they can lead better lives,' Nghiemphu said. Humor, advocacy helped them cope While they were close before they learned they had NF1-PN, the condition brought Michelle and Samantha closer. Michelle said humor helped strengthen their bond. 'I would mock her. I don't mean that in a nasty way but I had to make her laugh. It kind of stinks. Why my kid? Why is this happening? We tried really hard to laugh at everything,' she said. When Samantha complained about the pain in her plexiform, they nicknamed it plexi, referring to it in a silly, whiny voice. 'I'd say, 'My plexi, you're hurting me,'' said Samantha. Then they'd laugh together. While waiting at the hospital, she also relied on her mom's humor to help pass the time. She recalled a time they waited in radiology for images and played the game Heads Up. 'We were shaking money makers and my dad said, 'I'm not doing that, that's all you.' We wrestled, we stop drop and rolled,' said Samantha. Michelle went all out. 'I know people were staring at us, but the fact of the matter is that everyone who was staring was wishing their mom was just as much of a lunatic as I am and that they were playing it too,' she said. 'If I can keep one mom from feeling that fear because Samantha and I are making fun of each other, then awesome.' They also share a passion for spreading awareness about NF1-PN by speaking and attending events with the Neurofibromatosis Network and the Children's Tumor Foundation. Samantha has also advocated on Capitol Hill and continues to share her story to inspire others. 'I let [this disease] define me for a while, and I was told I was never going to dance again, and dance was my first passion and first love, and two years later, after my first surgery, I was back dancing on my high school dance team,' she said. While it wasn't easy, she also excelled academically in high school. Today, she is attending college and working toward becoming a certified nursing assistant as she aspires to eventually become a registered nurse.
