Retinal Vascular Occlusion

Friday, Oct 18, 2024 The ELEVATUM study showed clinically meaningful improvement in vision and reduction in retinal fluid in people with DME treated with Vabysmo who identify as African American, Black, Hispanic and LatinoEfficacy and safety from this Phase IV study were consistent with data from the Vabysmo Phase III DME studies These racial and ethnic groups are disproportionately affected by diabetes and at higher risk of developing DME, a leading cause of vision loss South San Francisco, CA -- October 18, 2024 -- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today positive topline one-year results from the open-label, single-arm Phase IV ELEVATUM study evaluating Vabysmo® (faricimab-svoa) for the treatment of diabetic macular edema (DME) in people from racial and ethnic groups that are often underrepresented in clinical trials. Initial data from 124 participants in the United States showed that after one year of treatment with Vabysmo, administered every eight weeks, participants could read an additional 12.3 letters on average – equivalent to about two and a half lines on an eye chart. Results among major racial and ethnic groups represented in this study were similar. Hispanic and Latino participants started the study with the most severe disease and had an average vision gain of 14.1 letters from baseline at one year, equivalent to nearly three lines on an eye chart. African American and Black participants gained an average of 11.3 letters from baseline at one year. Vabysmo was well tolerated, with no new safety events identified. These data were presented in a late-breaking oral presentation at the American Academy of Ophthalmology (AAO) 2024 Annual Meeting in Chicago on October 18. The study is the first retina trial for historically underrepresented populations. “Vabysmo has been shown to be an effective first-line treatment for diabetic macular edema, and for the first time, we now have data demonstrating its ability to improve vision in Black, African American, Hispanic, and Latino patients who are disproportionately impacted by this condition,” said investigator Jeremiah Brown, M.D., of Retina Consultants of Texas, who presented the data at AAO. “As a clinician who serves patients from these communities, I felt it was important to take part in this groundbreaking study and hope the findings will inform and improve the care we provide to our patients in the clinic daily.” Results were consistent with the Phase III YOSEMITE and RHINE DME studies. A secondary endpoint showed robust retinal drying with Vabysmo across these racial and ethnic groups, who, on average, achieved a decrease of 206.3 microns in central subfield thickness (CST) from baseline. Reducing CST indicates retinal drying, which is an important clinical measure, as swelling from excess fluid in the back of the eye is associated with distorted and blurred vision. “Though certain ethnic and racial groups are disproportionately affected by DME, they lag far behind in clinical trial representation,” said Gregory A. Rippon, M.D., M.S., vice president, U.S. Medical Affairs. “We conducted the ELEVATUM study to specifically address this issue and understand how underrepresented patient populations respond to treatment with Vabysmo to help deliver better, more equitable care, and change how clinical trials are designed in the future.” Among the 124 patients, 45% self-identified as Hispanic or Latino, and 48% as Black or African American. The study was designed to facilitate enrollment and promote retention of underrepresented patients. For example, ELEVATUM was conducted at sites that treat a high proportion of these populations, in urban, rural, and community-based locations. In addition, eligibility criteria allowed participants with a hemoglobin A1c (HbA1c) level up to 12%. An HbA1c test measures a person’s average blood sugar levels over the past three months and is used to diagnose diabetes. Typically, the threshold for DME trials is an HbA1c level of 10%. However, HbA1c levels can be higher in Black, African American, Hispanic and Latino populations compared with Caucasians, meaning a lower HbA1c threshold can inadvertently lead to the exclusion of patients from various ethnic and racial groups. “At Genentech we’re challenging the status quo and pioneering a new era of inclusive research that aims to directly address long standing health disparities,” said Quita Highsmith, vice president and chief diversity officer at Genentech. “The ELEVATUM study is a significant milestone that not only establishes a blueprint of best practices to enroll more diverse patients, but confirms our continued commitment to advancing inclusive research for all patients.” To date, Vabysmo is approved in more than 100 countries for DME and wet, or neovascular, age-related macular degeneration (AMD), and in over 30 countries for macular edema following retinal vein occlusion (RVO). More than five million doses of Vabysmo have been distributed globally since its initial U.S. approval in 2022. Genentech is committed to helping people access the medicines they are prescribed and offers comprehensive services for people prescribed Vabysmo to help minimize barriers to access and reimbursement. Patients can call 833-EYE-GENE for more information. For people who qualify, Genentech offers patient assistance programs through Genentech Access Solutions. More information is also available at (866) 4ACCESS/(866) 422-2377 or https://www.Genentech-Access.com. Visit https://www.Vabysmo.com for additional information. About ELEVATUM ELEVATUM (NCT05224102) is a Phase IV, multicenter, open-label, single-arm study designed to evaluate Vabysmo as a treatment for diabetic macular edema (DME) in patients that have been historically underrepresented in clinical trials, including people who self-identify as Black, African American, Hispanic or Latino. Trial participants have not been treated with an anti‑vascular endothelial growth factor before the study. They receive treatment every 4 weeks with Vabysmo up to week 20, followed by treatment every 8 weeks up to week 52. The primary endpoint is change from baseline in best corrected visual acuity at week 56. Secondary endpoints include safety and change in central subfield thickness from baseline over time. About Diabetic Macular Edema Affecting approximately 750,000 people in the United States, diabetic macular edema (DME) is a vision-threatening retinal condition associated with blindness and decreased quality of life when left untreated. DME occurs when damaged blood vessels in the retina leak into and cause swelling in the macula – the central area of the retina responsible for the sharp vision needed for reading and driving. The number of people with DME is expected to grow as the prevalence of diabetes increases. About the Vabysmo® (faricimab-svoa) Clinical Development Program Genentech has a robust Phase III clinical development program for Vabysmo. The program includes AVONELLE-X, an extension study of TENAYA and LUCERNE, evaluating the long-term safety and tolerability of Vabysmo in wet age-related macular degeneration (AMD), and RHONE-X, an extension study of YOSEMITE and RHINE, evaluating the long-term safety and tolerability of Vabysmo in diabetic macular edema (DME). The POYANG study is evaluating Vabysmo in adult treatment-naive patients with choroidal neovascularization secondary to pathologic myopia. Genentech has also initiated several Phase IV studies, including the ELEVATUM study of Vabysmo in underrepresented patient populations with DME and the SALWEEN study of Vabysmo in a subpopulation of people with wet AMD that is highly prevalent in Asia. Genentech has also initiated the VOYAGER study, a global real-world data collection platform, and supports several other independent studies to further understand retinal conditions with a high unmet need. About Vabysmo® (faricimab-svoa) Vabysmo is the first bispecific antibody approved for the eye. It targets and inhibits two signaling pathways linked to a number of vision-threatening retinal conditions by neutralizing angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A). While research is underway to better understand the role of the Ang-2 pathway in retinal disease, Ang-2 and VEGF-A are thought to contribute to vision loss by destabilizing blood vessels, which may cause new leaky blood vessels to form and increase inflammation. By blocking pathways involving Ang-2 and VEGF-A, Vabysmo is designed to stabilize blood vessels. Vabysmo U.S. Indications Vabysmo (faricimab-svoa) is a prescription medicine given by injection into the eye, used to treat adults with neovascular (wet) age‑related macular degeneration (AMD), diabetic macular edema (DME) and macular edema following retinal vein occlusion (RVO). Important Safety Information Contraindications Vabysmo is contraindicated in patients who have an infection in or around their eye, have active swelling around their eye that may include pain and redness, or are allergic to Vabysmo or any of the ingredients in Vabysmo. Warnings and Precautions Injections like the one for Vabysmo can cause an eye infection (endophthalmitis) or separation of layers of the retina (retinal detachment). Patients should seek medical care if they experience increasing eye pain, vision loss, sensitivity to light, or redness in the white of the eye. Vabysmo may cause a temporary increase in pressure in the eye (intraocular pressure), which occurs 60 minutes after the injection. Although not common, Vabysmo patients have had serious, sometimes fatal, problems related to blood clots, such as heart attacks or strokes (thromboembolic events). In clinical studies for wet AMD during the first year, 7 out of 664 patients treated with Vabysmo reported such an event. In DME studies from baseline to week 100, 64 out of 1,262 patients treated with Vabysmo reported such an event. In clinical studies for RVO during 6 months, 7 out of 641 patients treated with Vabysmo reported such an event. Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, have been reported with the use of Vabysmo. Healthcare providers should discontinue treatment with Vabysmo in patients who develop these events. Patients should be instructed to report any change in vision without delay. Adverse Reactions The most common adverse reactions (≥5%) reported in patients receiving Vabysmo were cataract (15%) and blood on the white of the eye (conjunctival hemorrhage, 8%). These are not all the possible side effects of Vabysmo. Pregnancy, Lactation, Females and Males of Reproductive Potential Based on how Vabysmo interacts with your body, there may be a potential risk to an unborn baby. Patients should use birth control before their first injection, during their treatment with Vabysmo, and for 3 months after their last dose of Vabysmo. It is not known if Vabysmo passes into breast milk. Patients should talk to their healthcare provider about the best way to feed their baby if they receive Vabysmo. Patients may report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. Patients may also report side effects to Genentech at (888) 835-2555. Please see additional Important Safety Information in the full Vabysmo Prescribing Information or visit https://www.Vabysmo.com. About Genentech in Ophthalmology Genentech is researching and developing new treatments for people living with a range of eye diseases that cause significant visual impairment and blindness, including wet age-related macular degeneration (AMD), diabetic macular edema (DME), diabetic retinopathy (DR), geographic atrophy (GA) and other retinal diseases, including rare and inherited conditions. 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 https://www.gene.com. ###

Doppler ultrasound measurement has a significant impact in medical research. The study focused on clinical data from 236 patients in Egypt, Ghana, Kenya, Nigeria, Oman, Saudi Arabia, the United States and the United Kingdom. Specifically, in the Phase III GBT440-032 trial, patients treated with Oxbryta experienced more frequent vascular occlusion crises (VOCs) than those treated without Oxbryta, and unfortunately eight deaths were recorded. As one of the most common acute complications in patients with SCD (sickle cell disease), the severity of VOC cannot be ignored. SCD, as a hereditary blood disorder, has a core pathology in which glutamate, the sixth amino acid in the β-peptide chain, is replaced by valine, which leads to the production of abnormal hemoglobin, sickle hemoglobin (HbS). The presence of HbS causes red blood cells to deform (sickle) and even destroy, and this abnormal form of red blood cells not only has a short life span, but also is easy to block small blood vessels, resulting in pain, breathing difficulties, hemolysis and a series of complex symptoms and complications. Oxbryta, as the first drug approved by the FDA to directly inhibit HbS polymerization, its mechanism is to effectively inhibit the polymerization process of HbS by improving the affinity of hemoglobin to oxygen, thus reducing the degree of deformation and destruction of red blood cells. In addition, a second trial, GBT440-042 (also known as RESOLVE/NCT05561140), which investigated Oxbryta for leg ulcers in 88 12-year-old patients enrolled in Brazil, Kenya, and Nigeria, reported eight deaths in its open-label phase. Of note, the Phase III GBT440-038 trial (NCT04188509), which was scheduled to evaluate the long-term safety of Oxbryta and its efficacy in improving SCD-related complications in participants who completed treatment in earlier clinical studies, has been suspended. In response to the deaths in the trial, the European Medicines Agency (EMA) stated that there is no conclusive evidence that Oxbryta directly caused the deaths of patients. Given that most of the patients involved are from Africa, it cannot be ruled out that some of the cases are related to infectious diseases such as malaria. In light of the above, the U.S. Food and Drug Administration (FDA) has issued an official bulletin urgently urging patients and healthcare providers not to discontinue treatment and advising providers to suspend prescribing Oxbryta. At the same time, patients who have taken the drug should immediately contact their health care provider to discuss and adjust treatment options. As a rare disease with autosomal dominant inheritance, SCD has been included in the first Rare Disease Catalogue in China. Its medical history dates back to the first reported case in 1910 by American physician James B. Herrick, which detailed a 20-year-old patient from Jamaica with a distinctive "sickle" or "crescent" shape of red blood cells. In 1949, a landmark study by E. Anthony Beutler and James V. Neel revealed the genetic nature of SCD and its pathological mechanism driven by mutations in a single gene. Subsequent studies further elucidated the genetic pattern of SCD and its potential protective effect against malaria infection. SCD usually develops in early childhood, and the severity of the condition varies from person to person. At present, treatment strategies mainly include blood transfusion and drug therapy. Among them, hydroxyurea as the first drug approved by the FDA for the treatment of SCD, its development history and efficacy have been widely recognized. In addition, with the advancement of medical technology, a variety of new drugs, including Oxbryta, as well as gene therapies such as Casgevy and Lyfgenia, are gradually being applied to the clinic, providing patients with more treatment options. However, considering the limited scope and high cost of gene therapy, its application in the field of SCD therapy still needs to be further evaluated and explored.

U.S. pharmaceutical giant Pfizer announced on Wednesday that it was withdrawing its sickle cell disease treatment Oxbryta (also known as Voxelotor) from all approved markets because of the risk of serious complications and death. Oxbryta was originally a product of Global Blood Therapeutics, and Pfizer acquired Oxbryta in 2022 for up to $5.4 billion. According to statistics, the treatment contributed $328 million to Pfizer's revenue in the full year 2023. However, based on the current review of clinical data, Pfizer believes that the benefits of Oxbryta no longer outweigh its potential risks and has decided to discontinue all research and market access programs related to Oxbryta. The company pointed out that the data reflect a significant imbalance in the incidence of vascular occlusion crisis, a potentially fatal complication of the disease, which needs further evaluation and discussion. An occlusive crisis usually occurs when blood flow is blocked, tissue is starved of oxygen and inflammation is triggered. The decision comes as the European Medicines Agency's Committee for Medicinal Products for Human Use plans to hold a special meeting on Thursday to consider Pfizer's drug. Notably, in a study involving 236 participants, eight of those treated with Oxbryta died, compared to just two in the placebo group. In response to this situation, Pfizer said that it will continue to analyze the existing data in depth and has informed the relevant regulatory authorities of the findings in a timely manner. In the meantime, the company recommends that all patients who are being treated with Oxbryta speak with a healthcare professional as soon as possible to explore possible alternative treatment options. Oxbryta was originally developed to treat a genetic blood disorder that causes red blood cells to form abnormally, which increases the risk of stroke, organ damage and premature death. Nevertheless, Pfizer stressed that the delisting decision is not expected to have a significant impact on its overall financial performance in 2024.