Veopoz™ (pozelimab-bbfg) Receives FDA Approval as the First Treatment for Children and Adults with CHAPLE Disease

CHAPLE is an ultra-rare hereditary disease that can cause potentially life-threatening gastrointestinal and cardiovascular symptoms

Approval represents 10^th 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

TARRYTOWN, N.Y., Aug. 18, 2023 (GLOBE NEWSWIRE) -- 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.

U.S. FDA-approved Indications
Veopoz is a prescription medicine used to treat:

• Adults and children 1 year of age and older with a disease called CD55-deficient protein-losing enteropathy (PLE), also known as CHAPLE disease.
  

It is not known if Veopoz is safe and effective in children younger than 1 year of age.

IMPORTANT SAFETY INFORMATION

What is the most important information I should know about VEOPOZ?
VEOPOZ is a medicine that affects your immune system and can lower the ability of your immune system to fight infections.

• VEOPOZ increases your chance of getting serious and life-threatening meningococcal infections that may quickly become life-threatening and cause death if not recognized and treated early.

1. You must receive meningococcal vaccines at least 2 weeks before your first dose of VEOPOZ if you have not already had these vaccines.
2. If you had a meningococcal vaccine in the past, you might need additional vaccination before starting VEOPOZ. Your healthcare provider will decide if you need additional meningococcal vaccination.
3. If your healthcare provider decides that urgent treatment with VEOPOZ is needed, and your meningococcal vaccines are not up-to-date, you should receive meningococcal vaccination as soon as possible. You should also receive antibiotics.
4. Meningococcal vaccines reduce the risk of meningococcal infection but do not prevent all meningococcal infections. Call your healthcare provider or get emergency medical care right away if you get any of these signs and symptoms of a meningococcal infection:
   • headache with nausea or vomiting
   • headache with a stiff neck or stiff back
   • fever and a rash
   • muscle aches with flu-like symptoms
   • headache and fever
   • fever
   • confusion
   • eyes sensitive to light

Your healthcare provider will give you a Patient Safety Card about the symptoms of meningococcal, or other infection. Carry it with you at all times during treatment and for 3 months after your last VEOPOZ dose. Your risk of meningococcal infection may continue for several weeks after your last dose of VEOPOZ. It is important to show this card to any healthcare provider who treats you. This will help them diagnose and treat you quickly.

VEOPOZ may also increase the risk of other types of serious bacterial infections.

• People who take VEOPOZ may have an increased risk of getting infections caused by Streptococcus pneumoniae and Haemophilus influenzae.
  
• Certain people may also have an increased risk of bacterial infection including gonorrhea infection. Talk to your healthcare provider to find out if you are at risk of gonorrhea infection, about gonorrhea prevention, and regular testing.
  

Call your healthcare provider right away if you have any new signs or symptoms of infection.

Do not receive VEOPOZ if you have a meningococcal infection.

Before you receive VEOPOZ, tell your healthcare provider about all of your medical conditions, including if you: have an infection or fever, are pregnant or plan to become pregnant, and are breastfeeding or plan to breastfeed. It is not known if VEOPOZ will harm your unborn baby or if it passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with VEOPOZ.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. It is important that you have all recommended vaccinations before you start VEOPOZ, receive antibiotics if you start VEOPOZ within 2 weeks of receiving meningococcal vaccination, and stay up to date with all recommended vaccinations during treatment with VEOPOZ.

VEOPOZ and other medicines may affect each other, causing side effects. VEOPOZ may affect the way other medicines work, and other medicines may affect how VEOPOZ works.
Especially tell your healthcare provider if you take Intravenous Immunoglobulin (IVIg).

Know the medicines you take and the vaccines you receive. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

What are the possible side effects of VEOPOZ?

VEOPOZ can cause serious side effects including allergic (hypersensitivity) reactions including infusion-related reactions, which may happen during your treatment. Tell your healthcare provider right away if you develop any of these symptoms or any other symptom during your VEOPOZ treatment that may mean you are having a serious allergic reaction:  chest pain, trouble breathing or shortness of breath, swelling of your face, tongue, or throat, and feel faint or pass out.

The most common side effects of VEOPOZ are upper respiratory tract infection, fracture, raised, red patches of skin that are often very itchy (hives), and hair loss (alopecia).

Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of VEOPOZ. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Please see the full Prescribing Information, including Boxed WARNING, and Medication Guide for VEOPOZ.

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.

For more information, please visit www.Regeneron.com or follow Regeneron on LinkedIn.

Forward-Looking Statements and Use of Digital Media
This press release includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals, Inc. (“Regeneron” or the “Company”), and actual events or results may differ materially from these forward-looking statements. Words such as “anticipate,” “expect,” “intend,” “plan,” “believe,” “seek,” “estimate,” variations of such words, and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. These statements concern, and these risks and uncertainties include, among others, the nature, timing, and possible success and therapeutic applications of products marketed or otherwise commercialized by Regeneron and/or its collaborators or licensees (collectively, “Regeneron’s Products”) and product candidates being developed by Regeneron and/or its collaborators or licensees (collectively, “Regeneron’s Product Candidates”) and research and clinical programs now underway or planned, including without limitation Veopoz™ (pozelimab-bbfg) for the treatment of adult and pediatric patients 1 year of age and older with CHAPLE disease as well as aflibercept 8 mg; uncertainty of the utilization, market acceptance, and commercial success of Regeneron’s Products (such as Veopoz) and Regeneron’s Product Candidates (such as aflibercept 8 mg) and the impact of studies (whether conducted by Regeneron or others and whether mandated or voluntary), including the study discussed in this press release, on any of the foregoing; the likelihood, timing, and scope of possible regulatory approval and commercial launch of Regeneron’s Product Candidates, such as aflibercept 8 mg (including the timing of any action by the U.S. Food and Drug Administration on the Biologics License Application for aflibercept 8 mg referenced in this press release), and new indications for Regeneron’s Products; the ability of Regeneron’s collaborators, licensees, suppliers, or other third parties (as applicable) to perform manufacturing, filling, finishing, packaging, labeling, distribution, and other steps related to Regeneron’s Products and Regeneron’s Product Candidates; the ability of Regeneron to manage supply chains for multiple products and product candidates; safety issues resulting from the administration of Regeneron’s Products (such as Veopoz) and Regeneron’s Product Candidates (such as aflibercept 8 mg) in patients, including serious complications or side effects in connection with the use of Regeneron’s Products and Regeneron’s Product Candidates in clinical trials; determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron’s ability to continue to develop or commercialize Regeneron’s Products and Regeneron’s Product Candidates; ongoing regulatory obligations and oversight impacting Regeneron’s Products, research and clinical programs, and business, including those relating to patient privacy; the availability and extent of reimbursement of Regeneron’s Products (such as Veopoz and, if approved, aflibercept 8 mg) from third-party payers, including private payer healthcare and insurance programs, health maintenance organizations, pharmacy benefit management companies, and government programs such as Medicare and Medicaid; coverage and reimbursement determinations by such payers and new policies and procedures adopted by such payers; competing drugs and product candidates that may be superior to, or more cost effective than, Regeneron’s Products and Regeneron’s Product Candidates; the extent to which the results from the research and development programs conducted by Regeneron and/or its collaborators or licensees may be replicated in other studies and/or lead to advancement of product candidates to clinical trials, therapeutic applications, or regulatory approval; unanticipated expenses; the costs of developing, producing, and selling products; the ability of Regeneron to meet any of its financial projections or guidance and changes to the assumptions underlying those projections or guidance; the potential for any license, collaboration, or supply agreement, including Regeneron’s agreements with Sanofi and Bayer (or their respective affiliated companies, as applicable) to be cancelled or terminated; the impact of public health outbreaks, epidemics, or pandemics (such as the COVID-19 pandemic) on Regeneron's business; and risks associated with intellectual property of other parties and pending or future litigation relating thereto (including without limitation the patent litigation and other related proceedings relating to EYLEA^® (aflibercept) Injection and REGEN-COV^® (casirivimab and imdevimab)), other litigation and other proceedings and government investigations relating to the Company and/or its operations, the ultimate outcome of any such proceedings and investigations, and the impact any of the foregoing may have on Regeneron’s business, prospects, operating results, and financial condition. A more complete description of these and other material risks can be found in Regeneron’s filings with the U.S. Securities and Exchange Commission, including its Form 10-K for the year ended December 31, 2022 and its Form 10-Q for the quarterly period ended June 30, 2023. Any forward-looking statements are made based on management’s current beliefs and judgment, and the reader is cautioned not to rely on any forward-looking statements made by Regeneron. Regeneron does not undertake any obligation to update (publicly or otherwise) any forward-looking statement, including without limitation any financial projection or guidance, whether as a result of new information, future events, or otherwise.

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Investor Relations Vesna Tosic     invest@regeneron.com