• Phase III HAVEN 7 primary data presented at ASH 2023 provide additional confidence in the favorable efficacy and safety profile of subcutaneous Hemlibra given soon after birth
• At nearly two years median follow-up in the descriptive, single-arm study, no babies experienced spontaneous bleeds requiring treatment, and all treated bleeds were as a result of trauma
• Safety results were consistent with previous studies of Hemlibra, with no new safety signals observed
• The HAVEN 7 study was developed in collaboration with the hemophilia A community to generate additional evidence for the prophylactic treatment of infants with hemophilia A

SOUTH SAN FRANCISCO, Calif. / Dec 09, 2023 / Business Wire / Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the primary analysis of the Phase III HAVEN 7 study reinforced the efficacy and safety of Hemlibra^® (emicizumab-kxwh) in previously untreated or minimally treated infants with severe hemophilia A without factor VIII inhibitors. Results showed that Hemlibra achieved meaningful bleed control in babies up to 12 months of age and was well tolerated. The new data were presented at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition taking place December 9-12, 2023 in San Diego, California and included in the press program.

“Hemophilia A can have a devastating impact on any patient, but this is especially true for infants, where the emotional and physical stress due to frequent hospital visits, treatment administration and other worries can be distressing for babies and their parents and caregivers,” said Steven Pipe, M.D., professor of pediatrics and pathology at the University of Michigan. “These results reinforce the benefit of starting prophylaxis as soon as possible after birth, as well as for the use of subcutaneous treatments, which are especially valuable in young babies where access to veins can be very difficult.”

The burden of severe hemophilia A in babies and on their parents and caregivers is significant. The World Federation of Hemophilia treatment guidelines consider the standard of care in hemophilia to be regular prophylaxis initiated at a young age, as studies have shown this improves long-term outcomes, while reducing the risk of intracranial hemorrhage. However, for many babies with hemophilia A, prophylaxis is not started until after the first year of life because of the high treatment burden. Hemlibra, which is already approved and being used to treat babies with hemophilia A, provides a flexible treatment option that can be administered subcutaneously from birth at different dosing frequencies.

“The results of HAVEN 7 provide additional confidence in the efficacy and safety profile of Hemlibra for babies with severe hemophilia A and add to its extensive clinical and real-world evidence across all ages,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “Conducted in collaboration with the hemophilia A community, this trial reflects our ongoing commitment to listen and respond to the needs of those impacted by this condition in hopes of advancing treatment standards even further.”

The HAVEN 7 study is a Phase III, descriptive, single-arm study set up in collaboration with the hemophilia A community to evaluate the efficacy, safety, pharmacokinetics and pharmacodynamics of subcutaneous Hemlibra in infants with severe hemophilia A without factor VIII inhibitors. These results, which included data from 55 participants, showed that at 101.9 weeks median follow-up, 54.5% of participants (n=30) did not have any bleeds that required treatment, while 16.4% (n=9) did not have any treated or untreated bleeds at all. There were no spontaneous bleeds requiring treatment in any participant, and all treated bleeds were as a result of trauma. A total of 207 bleeds occurred in 46 participants (83.6%); 87.9% of these were as a result of trauma. The model-based annualized bleeding rate (95% CI) was 0.4 (0.30–0.63) for treated bleeds. No new safety signals were observed and there were no treatment-related serious adverse events, intracranial hemorrhages or deaths reported. Just 3.6% of participants (n=2) tested positive for factor VIII inhibitors, which may be a consequence of reduced factor VIII usage in participants treated with Hemlibra, and no participant tested positive for anti-drug antibodies. Results were consistent with positive results from the interim analysis and from previous Phase III HAVEN studies.

The results of additional research on biomarkers in the HAVEN 7 study were also presented at ASH and were supportive of the study’s primary efficacy analysis. This additional research showed that the pharmacodynamic profiles of Hemlibra in babies were consistent with those previously observed in older children and adults with hemophilia A. The data showed that Hemlibra exhibits the expected pharmacodynamic response despite the reduced presence of the clotting factors that Hemlibra binds to in this age group.

The Phase III HAVEN 7 study results complement data from the broader, pivotal HAVEN clinical program, providing insights into the evolution of hemophilia A in babies, and the impact of initiating preventative treatment from birth. The primary analysis is being followed by a seven-year extension period. Hemlibra continues to redefine standards of care in hemophilia A as a flexible treatment option approved across all ages and stages of life regardless of inhibitor status and at different dosing frequencies. It is approved for the routine prophylaxis of people with hemophilia A in more than 115 countries worldwide. It has been studied in one of the largest clinical trial programs in people with hemophilia A with and without factor VIII inhibitors, including eight Phase III studies.

About Hemlibra

Hemlibra is a bispecific factor IXa- and factor X-directed antibody. It is designed to bring together factor IXa and factor X, proteins required to activate the natural coagulation cascade and restore the blood clotting process for hemophilia A patients. Hemlibra is a prophylactic (preventative) treatment that can be administered by an injection of a ready-to-use solution under the skin (subcutaneously) once weekly, every two weeks or every four weeks. Hemlibra was created by Chugai Pharmaceutical Co., Ltd. and is being co-developed globally by Chugai, Roche and Genentech.

Hemlibra U.S. Indication

Hemlibra is a prescription medicine used for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children, ages newborn and older, with hemophilia A with or without factor VIII inhibitors.

Important Safety Information

What is the most important information to know about Hemlibra?

Hemlibra increases the potential for blood to clot. People who use activated prothrombin complex concentrate (aPCC; Feiba^®) to treat breakthrough bleeds while taking Hemlibra may be at risk of serious side effects related to blood clots.

These serious side effects include:

• Thrombotic microangiopathy (TMA), a condition involving blood clots and injury to small blood vessels that may cause harm to one’s kidneys, brain, and other organs
• Blood clots (thrombotic events), which may form in blood vessels in the arm, leg, lung, or head

Patients should talk to their doctor about the signs and symptoms of these serious side effects, which can include

• Confusion
• Stomach, chest, or back pain
• Weakness
• Nausea or vomiting
• Swelling, pain, or redness
• Feeling sick or faint
• Decreased urination
• Swelling of arms and legs
• Yellowing of skin and eyes
• Eye pain, swelling, or trouble seeing
• Fast heart rate
• Numbness in your face
• Headache
• Shortness of breath
• Coughing up blood

If patients experience any of these symptoms during or after treatment with Hemlibra, they should get medical help right away.

Patients should carefully follow their healthcare provider’s instructions regarding when to use an on demand bypassing agent or factor VIII, and the dose and schedule to use for breakthrough bleed treatment. If aPCC (Feiba^®) is needed, patients should talk to their healthcare provider in case they feel they need more than 100 U/kg of aPCC (Feiba^®) total.

Patients’ bodies may make antibodies against Hemlibra, which may stop Hemlibra from working properly. Patients should contact their healthcare provider immediately if they notice that Hemlibra has stopped working for them (e.g., increase in bleeds).

The most common side effects of Hemlibra include: injection site reactions (redness, tenderness, warmth, or itching at the site of injection), headache, and joint pain. These are not all of the possible side effects of Hemlibra. Patients can speak with their healthcare provider for more information.

What else should patients know about Hemlibra?

Patients should see the detailed “Instructions for Use” that comes with Hemlibra for information on how to prepare and inject a dose of Hemlibra, and how to properly throw away (dispose of) used needles and syringes.

• Patients should stop taking their prophylactic bypassing therapy the day before they start Hemlibra
• Patients may continue taking their prophylactic factor VIII for the first week of Hemlibra

Hemlibra may interfere with laboratory tests that measure how well blood is clotting and create an inaccurate result. Patients should speak with their healthcare provider about how this may affect their care.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Patients should only use Hemlibra for the condition it was prescribed. Patients should not give Hemlibra to other people, even if they have the same symptoms that they have. It may harm them.

Patients should tell their healthcare provider about all the medicines they take, including prescription medicines, over-the-counter medicines, vitamins, or herbal supplements. Patients should keep a list of them to show their healthcare provider and pharmacist.

Before using Hemlibra, patients should tell their healthcare provider about all of their medical conditions, including if they are pregnant, plan to become pregnant, are breastfeeding, or plan to breastfeed.

Since Hemlibra was tested in males, there is no information on whether Hemlibra may impact an unborn baby or breast milk. Females who are able to become pregnant should use birth control during treatment.

Side effects may be reported to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. Side effects may also be reported to Genentech at (888) 835-2555.

Please see Important Safety Information, including Serious Side Effects, as well as the Hemlibra full Prescribing Information and Medication Guide.

About hemophilia A

Hemophilia A is an inherited, serious disorder in which a person’s blood does not clot properly, leading to uncontrolled and often spontaneous bleeding. Hemophilia affects around 20,000 people in the United States, with hemophilia A being the most common form and approximately 50-60% of people living with a severe form of the disorder.

People with hemophilia A either lack or do not have enough of a clotting protein called factor VIII. In a healthy person, when a bleed occurs, factor VIII brings together the clotting factors IXa and X, which is a critical step in the formation of a blood clot to help stop bleeding. Depending on the severity of their disorder, people with hemophilia A can bleed frequently, especially into their joints or muscles. These bleeds can present a significant health concern as they often cause pain and can lead to chronic swelling, deformity, reduced mobility and long-term joint damage.

A serious complication of treatment is the development of inhibitors to factor VIII replacement therapies. Inhibitors are antibodies developed by the body’s immune system that bind to and block the efficacy of replacement factor VIII, making it difficult, if not impossible, to obtain a level of factor VIII sufficient to control bleeding.

About Genentech in hemophilia

In 1984, Genentech scientists were the first to clone recombinant factor VIII in response to the contaminated hemophilia blood supply crisis of the early 1980s. For more than 20 years, Genentech has been developing medicines to bring innovative treatment options to people with diseases of the blood within oncology, and in hemophilia A. Genentech is committed to improving treatment and care in the hemophilia community by delivering meaningful science and clinical expertise. For more information visit http://www.gene.com/hemophilia.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.