Rubella Syndrome, Congenital

An international team developed a new model, based on a case study of Nigeria, that may help public health officials accelerate the introduction of rubella vaccination in countries that have yet to do so. When public health officials make policies about when and how vaccination programs are implemented, they must weigh the benefits and risks of how infectious diseases spread throughout the country. However, these analyses are often based on national-level data and, in some countries, may overlook nuances at the local level. A new analysis by an international team, including Penn State researchers, revealed that the resulting recommendations may keep some countries from realizing the benefits of vaccination and globally eradicating diseases, such as rubella -- a contagious viral infection that causes mild symptoms in children. The team examined data from Nigeria, one of 19 countries that hasn't yet introduced rubella vaccination, as a case study. Their findings were published in the journal Vaccine. "It's this interesting challenge where rubella is a mild disease if you get it as a kid, but it's high risk if you get it as an adult," said senior author Matthew Ferrari, professor of biology and director of the Center for Infectious Disease Dynamics at the Huck Institutes of Life Sciences at Penn State. "All of the policy surrounding rubella vaccination has been guided by that risk in adults, which has been holding back the benefit of rubella vaccination in some countries." The primary concern among adults is the potential risk for congenital rubella syndrome (CRS), a serious health condition that can occur if a pregnant person contracts the virus. When an infectious disease like rubella is common, people are more likely to contract it earlier in life. And because the rubella virus is immunizing, those who are infected as children won't have pregnancies at risk of CRS when they are older. Vaccination, on the other hand, reduces the amount of circulating virus, meaning individuals who were not vaccinated as children are less likely to be infected with rubella by adolescence or adulthood, Ferrari explained. As a result, even as the total number of rubella cases goes down with vaccination, the number of rubella infections in people of reproductive age -- who were neither infected nor vaccinated as children -- increases, putting those pregnancies at risk of CRS. Because of this complex dynamic, the World Health Organization (WHO) recommends that countries demonstrate that they can achieve a coverage level of 80% or greater, through either routine immunization or supplemental campaigns, before introducing rubella vaccination. The conventional wisdom has been that when vaccination coverage is above this threshold, the reduced risk of CRS due to less rubella virus offsets the paradoxical increase in CRS risk because infections tend to happen later in life, Ferrari explained. The research team, working in partnership with the U.S. Centers of Disease Control and Prevention and the Nigeria Centre for Disease Control and Prevention, studied the epidemiology of rubella in Nigeria. Rubella is a comparatively rare disease, so it's difficult to quantify the potential harm and risk of CRS. These assessments are further complicated by the fact that Nigeria, Ferrari said, is a country with disparate ranges of wealth, vaccination coverage, health care access and birth rates, all of which play a role in infection and CRS risk. To gain a better understanding of the factors at play, the team analyzed data from a nationally representative serosurvey, which detects the presence of antibodies in blood. The data allowed the researchers to see how many people, particularly women of reproductive age, had rubella antibodies, how many were potentially at risk of rubella infection and where the infection risk was greatest geographically. They identified regional differences in transmission between the northern versus southern part of the country, finding that transmission in the north was two-times higher compared to the south. They were also able to estimate the number of pregnancies affected by rubella infection today. "We grounded the current infection risk and potential pregnancies at risk in strong empirical data and real-world phenomena," Ferrari said. "Parts of the country can already vaccinate more than 80% of kids, based on their current rate of measles vaccination, but low vaccination coverage in the north is a barrier to introduction across the whole country under the current recommendation." What's more, the concern about increased CRS cases may not be as bad as conventionally believed, Ferrari noted. The team's new estimates of transmission rates show that the 80% threshold is conservative and that introducing a rubella vaccination program in Nigeria today could reduce the number of CRS cases by thousands in the first five years. "Some states could see CRS risk increase by hundreds of cases," he said, "but that increased risk would not come to fruition until 10 years down the road" -- providing a decade for public health officials to implement policies and programs to prevent this possibility. "Strengthening and improving routine immunization programs and advancing them everywhere in the world is a benefit to everyone in the world. The more we do this, the elimination of rubella as a virus on this planet is entirely feasible," Ferrari said.

Once approved, Columvi will be the first CD20xCD3 T-cell-engaging bispecific antibody available to treat people in Europe with this aggressive lymphoma The recommendation is based on results from the phase I/II NP30179 study, where Columvi given as a fixed course induced early and long-lasting complete responses in people with heavily pre-treated or refractory diffuse large B-cell lymphoma1 Columvi is part of Roche’s industry-leading CD20xCD3 T-cell-engaging bispecific development programme, which aims to transform the treatment experience for people with blood cancers using off-the-shelf and fixed-duration options Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of Columvi® (glofitamab), for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy. Columvi has the potential to change the current standard of care in DLBCL. As well as inducing early and long-lasting responses in people with heavily pre-treated or refractory DLBCL, potentially allowing patients a treatment free period, Columvi is designed to be given for a fixed period of time so that people know when their treatment will end. It is also an off-the-shelf therapy, meaning that people do not have to wait for cell collection and genetic engineering before starting treatment, which could be particularly important for patients who are at a high-risk of their disease progressing. A final decision is expected from the European Commission (EC) in the near future. “New therapeutic options that are readily and broadly available are urgently needed for people with relapsing diffuse large B-cell lymphoma, which can become fatal without immediate treatment,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “The CHMP’s recommendation for Columvi brings us closer to providing a new, fixed-duration therapy for people with diffuse large B-cell lymphoma that induces early and long-lasting responses.” DLBCL is an aggressive (fast-growing) type of lymphoma and is one of the most prevalent types of blood cancer among adults.2 Each year in Europe, an estimated 36,000 people are diagnosed with DLBCL.3 While many people with DLBCL are responsive to initial treatment, four out of ten are not cured with the current frontline standard of care, and the majority of those who require subsequent lines of therapy have poor outcomes.4,5 Once approved, fixed-duration Columvi will be the first CD20xCD3 T-cell-engaging bispecific antibody available to treat people in Europe with this aggressive type of lymphoma following multiple prior lines of therapy. The CHMP recommendation is based on positive results from a pivotal cohort in the phase I/II NP30179 study, where Columvi given as a fixed-course induced early and long-lasting responses in people with R/R DLBCL. Overall, 83.3% of patients were refractory to their most recent therapy, 90% were refractory to any previous line of therapy, and about one-third (35.2%) had received prior CAR T-cell therapy. Results showed that Columvi given as a fixed course induced a complete response (CR; a disappearance of all signs of cancer) in 35.2% (n =38/108) of people and 50% (n=54/108) achieved an overall response (OR; the combination of CR and partial response, a decrease in the amount of cancer in their body). Among those who achieved a CR, 74.6% (95% CI: 59.19-89.93) continued to experience a response at 12 months, while the median duration of CR was not reached. The median follow-up for duration of response (DOR) was 12.8 months. Median time to first CR was 42 days (95% CI: 41-47). The most common adverse events (AEs) were cytokine release syndrome (CRS; 64.3%), neutropenia (a reduction in white blood cells [37.7%]), anaemia (30.5%) and thrombocytopenia (low blood platelet count [24.7%]). CRS was generally low grade (Grade 1: 48.1%; Grade 2: 12.3%). One patient discontinued treatment due to CRS.1 Additional data from a larger cohort in the NP30179 study, published in the New England Journal of Medicine, reinforce the durability of Columvi. Fixed-duration Columvi resulted in early and long-lasting responses in people with heavily pre-treated or refractory DLBCL, with 39.4% of patients (n=61/155) achieving a CR and a median DOR of 18.4 months. Median time to first CR was 42 days (95% CI: 42-44), with the majority of responses reported at the first scheduled response assessment (approximately 1.4 months after the start of treatment). Half of patients (51.6%; n=80/155) achieved an OR. The most common AE was CRS, which was generally low grade (Grade 1: 47.4%; Grade 2: 11.7%) and occurred at initial doses. Columvi-related AEs leading to treatment discontinuation occurred in 3.2% of patients.6 Columvi was recently approved by Health Canada for the treatment of adult patients with R/R DLBCL not otherwise specified, DLBCL arising from follicular lymphoma, or primary mediastinal B-cell lymphoma, who have received two or more lines of systemic therapy and are ineligible to receive or cannot receive CAR T-cell therapy or have previously received CAR T-cell therapy. Additionally, the U.S. Food and Drug Administration (FDA) accepted Genentech’s Biologics License Application and granted priority review for glofitamab for the treatment of people with R/R large B-cell lymphoma. The U.S. FDA is expected to make a decision on approval by 1 July 2023. Submissions to additional health authorities worldwide are ongoing. Columvi is part of Roche’s broad and industry-leading CD20xCD3 T-cell-engaging bispecific antibody clinical development programme. Roche’s portfolio also includes Lunsumio® (mosunetuzumab), which was granted accelerated approval by the U.S. FDA in December 2022 and conditional marketing authorisation by the EC in June 2022 for the treatment of adult patients with R/R follicular lymphoma after two or more lines of systemic therapy. In an effort to help more patients in need of new treatment options, Roche continues to expand Columvi’s clinical development programme, which includes the phase III STARGLO trial, evaluating Columvi in combination with gemcitabine and oxaliplatin (GemOx) versus rituximab in combination with GemOx in people with second-line plus DLBCL who are ineligible for autologous stem cell transplant. Additional phase III studies are also planned, including in first-line DLBCL. About Columvi® (glofitamab) Columvi is an investigational CD20xCD3 T-cell-engaging bispecific antibody designed to target CD3 on the surface of T-cells and CD20 on the surface of B-cells. Columvi was designed with a novel 2:1 structural format. This T-cell-engaging bispecific antibody is engineered to have one region that binds to CD3, a protein on T-cells, a type of immune cell, and two regions that bind to CD20, a protein on B-cells, which can be healthy or malignant. This dual-targeting brings the T-cell in close proximity to the B-cell, activating the release of cancer cell-killing proteins from the T-cell. A robust clinical development programme for Columvi is ongoing, investigating the molecule as a monotherapy and in combination with other medicines for the treatment of people with B-cell non-Hodgkin lymphomas, including diffuse large B-cell lymphoma and other blood cancers. About the NP30179 study The NP30179 study [NCT03075696] is a phase I/II, multicentre, open-label, dose-escalation and expansion study evaluating the safety, efficacy and pharmacokinetics of Columvi® (glofitamab) in people with relapsed or refractory diffuse large B-cell lymphoma. Outcome measures include complete response rate by an independent review committee (primary endpoint), overall response rate, duration of response, progression-free survival, safety, and tolerability (secondary endpoints). About diffuse large B-cell lymphoma (DLBCL) DLBCL is the most common form of non-Hodgkin lymphoma (NHL), accounting for about one in three cases of NHL. DLBCL is an aggressive (fast-growing) type of NHL.2 While it is generally responsive to treatment in the frontline, as many as 40% of people will relapse or have refractory disease, at which time salvage therapy options are limited and survival is short.4,5 Each year in Europe, it is estimated that 36,000 people are diagnosed with DLBCL.3 About Roche in haematology Roche has been developing medicines for people with malignant and non-malignant blood diseases for more than 20 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera®/Rituxan® (rituximab), Gazyva®/Gazyvaro® (obinutuzumab), Polivy® (polatuzumab vedotin), Venclexta®/Venclyxto® (venetoclax) in collaboration with AbbVie, Hemlibra® (emicizumab), Lunsumio® (mosunetuzumab) and Columvi® (glofitamab). Our pipeline of investigational haematology medicines includes a T-cell-engaging bispecific antibody cevostamab, targeting both FcRH5 and CD3; Tecentriq® (atezolizumab), a monoclonal antibody designed to bind with PD-L1 and crovalimab, an anti-C5 antibody engineered to optimise complement inhibition. Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further. About Roche Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. In recognising our endeavour to pursue a long-term perspective in all we do, Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the thirteenth consecutive year. This distinction also reflects our efforts to improve access to healthcare together with local partners in every country we work. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. References [1] Roche data on file. [2] Cancer.Net. Lymphoma - Non-Hodgkin: Subtypes. [Internet; cited April 2023]. Available from: https://www.cancer.net/cancer-types/lymphoma-non-hodgkin/subtypes. [3] Calculation for Worldwide incidence: World Health Organization. GLOBOCAN 2020, Cancer Incidence and Mortality: IARC CancerBase No. 11 [Internet; cited April 2023]. Available from: https://gco.iarc.fr/today/online-analysis-table?v=2020&mode=cancer&mode_population=continents&population=900&populations=908&key=asr&sex=0&cancer=39&type=0&statistic=5&prevalence=0&population_group=0&ages_group%5B%5D=0&ages_group%5B%5D=17&group_cancer=1&include_nmsc=1&include_nmsc_other=1#collapse-group-1-4-0. [4] Maurer MJ et al. Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy. J Clin Oncol. 2014;32:1066-73. [5] Sehn LH, Gascoyne RD. Diffuse large B-cell lymphoma: optimizing outcome in the context of clinical and biologic heterogeneity. Blood. 2015;125(1):22-32. [6] Dickinson MJ et al. Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. The New England Journal of Medicine. 2022. doi: 10.1056/NEJMoa2206913. The content above comes from the network. if any infringement, please contact us to modify.

RED BANK, N.J., Feb. 2, 2023 /PRNewswire/ -- Provention Bio, Inc. (Nasdaq: PRVB) (the "Company"), a biopharmaceutical company dedicated to intercepting and preventing immune-mediated diseases, today announced the close of the $40 million second tranche under the previously announced term loan facility of up to $125 million with Hercules Capital, Inc. (NYSE: HTGC), a leader in customized financing for companies in life sciences. "Exercising the second tranche of this term loan facility provides the anticipated additional capital to advance the commercial launch of TZIELD® as we continue to build awareness of our paradigm shifting therapeutic option to delay the onset of Stage 3 type 1 diabetes in those 8 years and older with Stage 2 T1D," noted Ashleigh Palmer, Co-Founder and CEO of Provention Bio. "We are very pleased with the reception that TZIELD® has received from patients and prescribers in the early days of our launch. We are also pleased to see the rapid and positive response from payers to TZIELD®, with most coverage policies published to date reflecting coverage to label, including United Healthcare and Anthem. During the first half of January, we completed the launch meetings for both our Provention commercialization team and our copromotion partners at Sanofi. With the help of our COMPASS Navigator patient services team, a number of patients have already received prior authorization approval and completed a full 14-day course of TZIELD®, with many more in the process of scheduling their infusions. We are grateful for the expertise and dedicated support of our employees and for partners like Sanofi and Hercules who have been instrumental in helping us provide access to TZIELD® for the stage 2 T1D individuals who need and can benefit from it." "We are proud to partner with Provention during this exciting time in the Company's history," said Bryan Jadot, Senior Managing Director and Life Sciences Group Head at Hercules Capital. "This substantial capital commitment from Hercules is testament to our confidence in Provention's ability to deliver on their important mission to intercept and prevent otherwise debilitating and life-threatening immune-mediated diseases like T1D." Under the terms of the term loan facility dated August 31, 2022, Hercules agreed to provide for up to $125 million of term loans in the aggregate, available to be funded in up to five tranches. The first tranche in an amount equal to $25 million was drawn at transaction close. Following the United States Food and Drug Administration (FDA) approval of TZIELD®, the Company has exercised the second tranche in an amount equal to $40 million. The third and fourth tranches will be available to the Company in an aggregate amount of up to $35 million, subject to satisfaction of certain conditions, including achievement of certain milestones. The availability of the fifth tranche of up to $25 million is subject to the approval of the lenders. On February 2nd, Provention Bio and Hercules Capital agreed to amend and restate the definition of "Term Loan Interest Rate" in the Loan and Security Agreement, dated August 31, 2022, to mean, for any day, a per annum rate of interest equal to the greater of either (i) the prime rate as reported in The Wall Street Journal plus 2.20% and (ii) 8.20%. This favorably compares to the previous definition of the greater of either (i) the prime rate as reported in The Wall Street Journal plus 2.70% and (ii) 8.20%. About TZIELD® TZIELD (teplizumab-mzwv) is a CD3-directed antibody indicated to delay the onset of Stage 3 T1D in adults and pediatric patients aged 8 years and older with Stage 2 T1D. TZIELD injection is supplied as a sterile, preservative-free, clear and colorless solution in a 2 mg/2 mL (1 mg/mL) single-dose vial for intravenous use. TZIELD should be administered by intravenous infusion (over a minimum of 30 minutes) once daily for 14 days. Please see full prescribing information for the dosing schedule. If a patient needs help paying for TZIELD, Provention Bio's Patient Assistance Program may be able to help. While co-pay amounts vary based on individual coverage, with the Provention Bio Copay Program, commercially or privately insured individuals enrolled in COMPASS may pay as little as $0 for TZIELD. If a patient qualifies, their COMPASS Navigator can help enroll them into the program so they may be able to lower their out-of-pocket costs. Interested patients and healthcare providers can contact COMPASS for questions about our available assistance programs at [email protected] and 1-844-778-2246, Monday through Friday from 8AM-8PM EST. Important Safety Information about TZIELD® WARNINGS AND PRECAUTIONS Cytokine Release Syndrome (CRS): CRS occurred in TZIELD-treated patients during the treatment period and through 28 days after the last drug administration. Prior to TZIELD treatment, premedicate with antipyretics, antihistamines and/or antiemetics, and treat similarly if symptoms occur during treatment. If severe CRS develops, consider pausing dosing for 1 day to 2 days and administering the remaining doses to complete the full 14-day course on consecutive days; or discontinue treatment. Monitor liver enzymes during treatment. Discontinue TZIELD treatment in patients who develop elevated alanine aminotransferase or aspartate aminotransferase more than 5 times the upper limit of normal (ULN) or bilirubin more than 3 times ULN. Serious Infections: Use of TZIELD is not recommended in patients with active serious infection or chronic infection other than localized skin infections. Monitor patients for signs and symptoms of infection during and after TZIELD administration. If serious infection develops, treat appropriately, and discontinue TZIELD. Lymphopenia: In clinical trials, lymphopenia occurred in 78% of TZIELD-treated patients. For most patients, lymphocyte levels began to recover after the fifth day of treatment and returned to pretreatment values within two weeks after treatment completion and without dose interruption. Monitor white blood cell counts during the treatment period. If prolonged severe lymphopenia develops (<500 cells per mcL lasting 1 week or longer), discontinue TZIELD. Hypersensitivity Reactions: Acute hypersensitivity reactions including serum sickness, angioedema, urticaria, rash, vomiting and bronchospasm occurred in TZIELD-treated patients. If severe hypersensitivity reactions occur, discontinue TZIELD and treat promptly. Vaccinations: The safety of immunization with live-attenuated (live) vaccines in TZIELD-treated patients has not been studied. TZIELD may interfere with immune response to vaccination and decrease vaccine efficacy. Administer all age-appropriate vaccinations prior to starting TZIELD. Administer live vaccines at least 8 weeks prior to treatment. Live vaccines are not recommended during treatment, or up to 52 weeks after treatment. Administer inactivated (killed) vaccines or mRNA vaccines at least 2 weeks prior to treatment. Inactivated vaccines are not recommended during treatment, or 6 weeks after completion of treatment. ADVERSE REACTIONS: Most common adverse reactions (>10%) were lymphopenia, rash, leukopenia, and headache. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088 or contact Provention Bio at 1-844-778-2246. USE IN SPECIFIC POPULATIONS Pregnancy: May cause fetal harm. Lactation: A lactating woman may consider pumping and discarding breast milk during and for 20 days after TZIELD administration. Please see accompanying Prescribing Information. About Sanofi US Co-Promotion In October 2022, Provention entered into a co-promotion agreement with Sanofi U.S. for the launch of TZIELD. Under the terms of the agreement, Sanofi will commit commercial resources in the United States, including diabetes field specialists, account directors, field-based reimbursement, and medical science liaisons to expand the number of key healthcare professionals reached in the United States. In exchange, Provention will reimburse field force-related expenses that Sanofi will incur in connection with commercializing teplizumab under the agreement. Provention retains all rights to TZIELD and maintains responsibility for the commercialization strategy. About Provention Bio, Inc. Provention Bio, Inc. (Nasdaq: PRVB) is a commercial-stage biopharmaceutical company focused on advancing the development and commercialization of investigational therapies that may intercept and prevent debilitating and life-threatening immune-mediated diseases. The Company's pipeline includes clinical-stage product candidates that have demonstrated in pre-clinical or clinical studies proof-of-mechanism and/or proof-of-concept in autoimmune diseases, including T1D, celiac disease and lupus. Visit www.ProventionBio.com for more information and follow us on Twitter: @ProventionBio. Internet Posting of Information Provention Bio, Inc. uses its website, www.proventionbio.com, as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation F.D. Such disclosures will be included on the Company's website in the "News" section. Accordingly, investors should monitor this portion of the Company's website, in addition to following its press releases, SEC filings and public conference calls and webcasts.