Protein-Losing Enteropathies

CHAPLE is an ultra-rare hereditary disease that can cause potentially life-threatening gastrointestinal and cardiovascular symptoms Approval represents 10th FDA-approved medicine invented by Regeneron With the approval of Veopoz, the pre-approval inspection issues related to the aflibercept 8 mg biologics license application (BLA) have been addressed FDA action on the aflibercept 8 mg BLA is expected in the next few weeks Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced the U.S. Food and Drug Administration (FDA) has approved Veopoz™ (pozelimab-bbfg) for the treatment of adult and pediatric patients 1 year of age and older with CHAPLE disease, also known as CD55-deficient protein-losing enteropathy. Veopoz is the first and only treatment indicated specifically for CHAPLE. With the approval of Veopoz, the pre-approval inspection issues related to the aflibercept 8 mg BLA have been addressed. FDA action on the aflibercept 8 mg BLA is expected in the next few weeks. “Most patients with CHAPLE disease are children who face severely debilitating symptoms and often life-threatening complications that begin in infancy,” said Michael Lenardo, M.D., Chief, Molecular Development of the Immune System Section; Co-Director, Clinical Genomics Program, National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH). “As an investigator in this pivotal trial and one of the discoverers of this disease, I saw first-hand the transformational clinical improvement that pozelimab achieves in those suffering from CHAPLE. The approval of pozelimab is a milestone to celebrate, providing a new medicine that can help these long-suffering patients.” CHAPLE is an ultra-rare and life-threatening hereditary immune disease driven by an overactivation of the complement system. In healthy individuals, the complement system is a mechanism for destroying microbes. However, those living with CHAPLE are unable to regulate complement activity due to mutations in their CD55 gene. Without proper CD55 regulation, the complement system may attack normal cells, causing damage to blood and lymph vessels along the upper digestive tract and leading to the loss of circulating proteins. There are fewer than 10 patients with CHAPLE disease identified in the U.S. Veopoz, a fully human monoclonal antibody, is designed to target complement factor C5, a protein involved in complement system activation. “As the first-ever treatment for CHAPLE, Veopoz is a testament to our commitment to uncovering genetic insights and applying them to the development of effective treatments for patients in need – regardless of the prevalence of their disease,” said George D. Yancopoulos, M.D., Ph.D., Board co-Chair, President and Chief Scientific Officer at Regeneron. “Beyond CHAPLE, we believe Veopoz has promise in a variety of complement-mediated diseases and are driving forward several clinical programs to explore its broader potential.” Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors. Meningococcal infections may become rapidly life-threatening or fatal if not recognized and treated early. Complete or update meningococcal vaccination at least two weeks prior to administering the first dose of Veopoz, unless the risks of delaying therapy outweigh the risks of developing meningococcal infection. If urgent therapy is indicated in a patient who is not up-to-date with both meningococcal vaccines according to Advisory Committee on Immunization Practices (ACIP) recommendations, administer meningococcal vaccines as soon as possible and provide the patient with antibacterial drug prophylaxis. Vaccination reduces, but does not eliminate, the risk of meningococcal infections. Regeneron is committed to helping people with rare diseases access their medications. Assistance for eligible CHAPLE patients, including information on treatment, insurance coverage, and financial support, will be available through Regeneron’s myRARE™ patient support program. Patients can call 1-833-4my-RARE (1-833-469-7273) for more information. Healthcare providers with questions regarding Veopoz access outside the United States can contact Clinigen at medicineaccess@clinigengroup.com and register for an account to request access at https://www.clinigengroup.com/direct/en/invitation-form/. Veopoz was reviewed under Priority Review, and the Company received a Rare Pediatric Disease Priority Review voucher upon approval. Veopoz was previously granted Rare Pediatric Disease designation, Orphan Disease designation and Fast Track designation. About the Pivotal CHAPLE Trial The FDA approval is based on results from a Phase 2/3 open-label trial that investigated the efficacy and safety of pozelimab in 10 patients aged 3 to 19 (median of 8.5 years). Patients were given a single loading dose of pozelimab 30 mg/kg intravenously on day 1, followed by subcutaneous weekly weight-based doses of pozelimab. All ten patients achieved normalization of serum albumin and serum IgG concentrations by week 12 and maintained these concentrations through at least 72 weeks of treatment. Five of the 10 patients received a total of 60 albumin transfusions in the 48 weeks prior to treatment. In the 48 weeks after starting treatment, one patient received one albumin transfusion. Nine of the 10 patients were hospitalized for a total of 268 days in the 48 weeks prior to treatment. In the 48 weeks after starting treatment, two patients were hospitalized for a total of 7 days. The most common adverse reactions occurring in two or more patients included upper respiratory tract infection, fracture, urticaria, and alopecia. About Veopoz Veopoz was invented using Regeneron’s proprietary VelocImmune® technology and is a fully human, monoclonal antibody designed to block the activity of complement factor C5 and prevent diseases mediated by the complement pathway. It is an IgG4 antibody that binds with high affinity to wild-type and variant human C5. As part of its ongoing development program, Veopoz is also being evaluated in combination with Alnylam’s cemdisiran (siRNAi C5 inhibitor) as an investigational combination therapy for the treatment of other complement-mediated disorders including paroxysmal nocturnal hemoglobinuria (PNH) and myasthenia gravis (MG). This combination is currently under clinical development, and its safety and efficacy have not been evaluated by any regulatory authority. About Regeneron's VelocImmune® Technology Regeneron's VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron's co-Founder, President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite® technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create a substantial proportion of all original, FDA-approved fully human monoclonal antibodies currently available. This includes REGEN-COV® (casirivimab and imdevimab), Dupixent® (dupilumab), Libtayo® (cemiplimab-rwlc), Praluent® (alirocumab), Kevzara® (sarilumab), Evkeeza® (evinacumab-dgnb) and Inmazeb® (atoltivimab, maftivimab and odesivimab-ebgn). About Regeneron Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led for 35 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous FDA-approved treatments and product candidates in development, almost all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, hematologic conditions, infectious diseases and rare diseases. Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite® technologies, such as VelocImmune®, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center®, which is conducting one of the largest genetics sequencing efforts in the world. The content above comes from the network. if any infringement, please contact us to modify.

The FDA has signed off on Regeneron and Bayer's high dose version of eye disease drug Eylea, setting up a market battle with Roche's fast-rising Vabysmo. Regeneron pulled off a rare double play on Friday afternoon as it scored two FDA approvals—one under the radar and the other highly anticipated. After the FDA signed off on Veopoz to treat ultra-rare Chaple disease, the United States regulator followed up with a nod for Regeneron’s high-dose version of blockbuster eye disease drug Eylea. The company revealed the approvals in a span of fewer than five hours. While the endorsement for Veopoz opens the treatment up to an extremely small patient population of around 100 people globally, the green light for HD Eylea covers millions who have wet age-related macular degeneration (AMD), diabetic macular edema (DME) and diabetic retinopathy (DR). It also kicks off a much anticipated market clash with Roche. The Eylea thumbs up comes after the FDA’s surprise rejection of the treatment in June because of an issue at the Bloomington, Indiana, plant of Regeneron’s contract manufacturer Catalent. Earlier this month, when Regeneron reported its second quarter earnings, the company said that Catalent would deliver information in the middle of August that could lead to approval by the end of the third quarter. With the news, Regeneron’s share price increased from $794 on Friday afternoon to $826 by mid-morning on Monday, a 4% gain. Regeneron and its Eylea partner Bayer are now set to take on Roche and its surging high-dose treatment Vabysmo, which has already gained blockbuster status this year despite being on the market for just 19 months. Regeneron will charge $2,625 per dose of HD Eylea. This compares to a $2,190 price for a vial of Vabysmo, which is a 6 mg dose. Regeneron will launch high-dose Eylea immediately, with customers able to order it "early this week," a company spokesperson wrote in an email. The approval "is a significant step for Regeneron to solidify its ophthalmology franchise and could allow for transitioning of new patient starts to Eylea HD ahead of new Eylea biosimilar entrants and increasing competition from Roche's Vabysmo,” Evan Seigerman, analyst with BMO Capital Markets, wrote in a note to clients. With its ability to extend injection intervals for many patients to once every four months, Vabysmo hit the market with much fanfare as an alternative to Eylea, which requires a shot every two months. But now Regeneron has answered with its 8 mg version of Eylea, which trials suggest has superior staying power.   Earlier this month, results of a phase 3 study showed that 88% of patients receiving 8 mg injections of Eylea over a two-year period were able to extend their dosage to at least 12-week intervals. The PULSAR study, which was conducted by Bayer, also showed that 71% of patients met the extension criteria for longer dosing intervals, with 47% of patients reaching 20 or more weeks and 28% reaching the criteria for 24-week intervals. As Regeneron has touted the staying power of Eylea, Roche has countered with results of trials that show that Vabysmo provides better drying of the retina than Eylea. Last month, at the American Society of Retina Specialists conference, Roche subsidiary Genentech presented a post-hoc analysis of pooled data from two trials which showed Vabysmo led to less fibrosis than Eylea in patients with diabetic macular edema (DME). Post-hoc data from these and other trials also showed that more than half of AMD and DME patients who were treated every 16 weeks with Vabysmo met criteria to extend their dosing intervals to every 20 weeks. As Vabysmo has gained steam—registering sales of 957 million Swiss francs ($1.1 billion) in the first half of this year—Eylea’s sales have stagnated. Its $1.5 billion generated in the second quarter matched the figure from the previous quarter and was a 7% decline from the same period in 2022.

Regeneron Pharmaceuticals’ Veopoz (pozelimab-bbfg) has been approved by the US Food and Drug Administration (FDA) to treat patients with an ultra-rare immune disease. The human monoclonal antibody has been specifically authorised for use in adult and paediatric patients aged one year and older with CHAPLE disease. Fewer than ten patients in the US have been diagnosed with the condition, which is also known as CD55-deficient protein-losing enteropathy. People with CHAPLE have a mutation in their CD55 gene, which regulates the body's mechanism for destroying microbes. Without proper regulation, the mechanism may start attacking normal cells in the body. Veopoz is now the first treatment indicated specifically for CHAPLE and is designed to target complement factor C5, a protein involved in complement system activation. The FDA’s decision is supported by results from a phase 2/3 trial that evaluated the safety and efficacy of the drug in ten patients aged three to 19 years, who were given a single loading dose of Veopoz intravenously on day one, followed by subcutaneous weekly weight-based doses. All ten patients achieved normalisation of serum albumin and serum IgG concentrations by week 12, the company said, and maintained those concentrations through at least 72 weeks of treatment. “As an investigator in this pivotal trial and one of the discoverers of this disease, I saw first-hand the transformational clinical improvement that [Veopoz] achieves in those suffering from CHAPLE,” said Michael Lenardo, chief of the molecular development and immune system section and the founder and co-director of the clinical genomics programme at the National Institute of Allergy and Infectious Disease, National Institutes of Health. As part of its ongoing development programme, Veopoz is also being evaluated in combination with Alnylam’s cemdisiran to treat other complement-mediated disorders, including paroxysmal nocturnal haemoglobinuria and myasthenia gravis. George Yancopoulos, Regeneron’s president and chief scientific officer, said: “As the first-ever treatment for CHAPLE, Veopoz is a testament to our commitment to uncovering genetic insights and applying them to the development of effective treatments for patients in need – regardless of the prevalence of their disease. “Beyond CHAPLE, we believe Veopoz has promise in a variety of complement-mediated diseases and are driving forward several clinical programmes to explore its broader potential.”