World Hepatitis Summit 2022 urges action to eliminate viral hepatitis as unexplained hepatitis cases in children rise globally

 The World Hepatitis Summit 2022 will review progress and renew commitments by global partners to accelerate action to achieve the global target of eliminating of viral hepatitis by 2030. 

 

At the 2016 World Health Assembly, countries made a historic commitment to eliminate viral hepatitis by 2030. Since 2016, countries have met the global 2020 target of reducing the incidence of hepatitis B in children under 5 and the number of people receiving treatment for hepatitis C has increased 10-fold.  

 

However, most countries failed to meet other 2020 targets. Timely access to the hepatitis B birth dose is still low in many low- and middle-income countries. Meanwhile, lack of awareness, limited political commitment, as well as stigma and discrimination continue to stop people accessing testing and care. It is estimated 354 million people globally are still living with this life-threatening infection and at least one person dies from viral hepatitis every 30 seconds. That’s over 1 million deaths per year – a greater toll than that from HIV and malaria combined. 

 

“Hepatitis is one of the most devastating diseases on earth, but it’s also one of the most preventable and treatable, with services that can be delivered easily and cheaply at the primary health care level,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General. 

 

“Many of the reasons people miss out on those services are the same reasons they miss out on services for other health challenges – accessibility and affordability, because of who they are, where they live or how much they earn. We call on all countries to commit to realising the dream of eliminating viral hepatitis by 2030, as part of a broader commitment to universal health coverage based on strong primary health care.” 

 

Most recently, in the months leading up to the Summit, some 700 cases of sudden and unexplained hepatitis in young children have come under investigation in 34 countries.Symptoms of this acute hepatitis come on quickly leading to a high proportion of children developing liver failure with a few requiring liver transplants. 

 

The Summit will showcase these epidemiologic updates and progress towards the commitment to eliminate hepatitis by 2030. In June 2021, WHO provided interim guidance on the criteria needs to achieve to be validated for the elimination of Hepatitis B and C viruses. Seven countries that have piloted these criteria will share their experiences and progress on the path to elimination.  

 

The new WHO Global Health Sector Strategy (GHSS) on viral hepatitis 2022-2030  recently reviewed and noted at the World Health Assembly, will play a strong part in this summit, the strategy contains operational and strategic shifts to ensure that globally we are on track to achieve the 2030 goal of ending the disease of viral hepatitis.  

 

This third World Hepatitis Summit will open with a high-level panel discussion featuring Dr Tedros Adhanom Ghebreyesus, Director-General, World Health Organization (WHO); Helen Clark, former Prime Minister, New Zealand; Professor Khaled Abdel Ghaffar, acting Health Minister, Egypt; Dr Tenu Avafia, Deputy Executive Director, Unitaid; and Charles Gore, Executive Director, Medicines Patent Pool. 

“Women’s and children’s health needs to be a top priority if we are to achieve hepatitis elimination by 2030. Hepatitis B is a major public health threat requiring collective efforts to advance universal vaccination of new-borns against Hepatitis B and prevent mother-to-child transmission” said Right Honourable Helen Clark, Former Prime Minister of New Zealand and Board Chair of PMNCH. 

Danjuma Adda, World Hepatitis Alliance President, said “we have come a long way, as a global community, in the drive towards hepatitis elimination. I thank the WHO and all partners for their support in this journey. We still have a long way to go to reach many populations affected by viral hepatitis. The World Hepatitis Summit promises to deliver on the power of the community, scientific and policy partnerships in driving the elimination goals of viral hepatitis.” 

The World Hepatitis Summit 2022 will be attended virtually by delegates from more than 100 countries, including world leaders, ministers of health, public health officials, medical professional, parliamentarians, academics and representatives from organizations of people affected by viral hepatitis.  

Elevation Oncology Announces the Presentation of New Preclinical Data in Pancreatic and Cholangiocarcinoma

Elevation Oncology, a  clinical stage biopharmaceutical company focused on the development of precision medicines for patients with genomically defined cancers, announced today the presentation by its collaborators in the Marc Ladanyi lab at Memorial Sloan Kettering (MSK) of further preclinical data on the specific inhibition of NRG1 fusion-induced tumorigenesis and signaling by seribantumab, a HER3 monoclonal antibody, at the American Association of Cancer Research Virtual Annual Meeting 2021. These data  in patient-derived xenograft (PDX) models of NRG1 fusion-positive pancreatic and cholangiocarcinoma build on earlier studies generated in lung and ovarian NRG1 fusion PDX models,, and further support the mechanistic rationale for the Phase 2 CRESTONE study for patients  with solid tumors of any origin harboring an NRG1 gene fusion. The CRESTONE study is currently enrolling at sites across the United States.

"Here we observed that NRG1 fusions activated HER3 and downstream signaling mediators such as AKT in a pancreatic cell line," said Igor Odintsov, MD, Research Fellow at MSK and lead author of the poster presentation. "Treatment with seribantumab was able to inhibit phosphorylation of the activated HER3 and AKT in the same cell line, and subsequent treatment of an APP-NRG1 fusion-positive pancreatic PDX model with seribantumab robustly inhibited tumor growth at clinically achievable doses."

Regressions were observed in all mice treated with 10 mg/kg BIW seribantumab, equivalent to a clinical dose of 2.6 g seribantumab in humans by allometric scaling. As in prior analysis in lung and ovarian NRG1 fusion PDX models, the pan-ERBB inhibitor afatinib was used as an active control in this pancreatic PDX model. No regression was observed in pancreatic PDX tumors treated with afatinib at 5 mg/kg QD.

NRG1 fusions have been identified in a variety of solid tumors, including lung, pancreatic, gallbladder, breast, ovarian, colorectal, neuroendocrine, cholangiocarcinomas, and sarcomas. Current data suggest that NRG1 fusions are predominantly mutually exclusive with other known driver alterations and are therefore considered to be the primary driver of the tumor's growth and proliferation.

"The rarity of competing oncogenic drivers in tumors driven by an NRG1 fusion presents a strong biological rationale for use of a targeted anti-HER3 monotherapy approach across tumor types. This approach is reflected in the design of our Phase 2 CRESTONE study as a tumor-agnostic study of monotherapy seribantumab with pre-defined exclusion of patients whose tumors harbor multiple actionable driver alterations," said Shawn M. Leland, PharmD, RPh, Founder and Chief Executive Officer of Elevation Oncology "In rare instances when multiple actionable driver alterations are identified in the same tumor, we believe there may be a similar biological rationale for addressing each driver alteration through combinations of agents targeted to each individual alteration, rather than the traditional combinations with chemotherapy. We are excited to report early results from preclinical exploration of this hypothesis, and look forward to continued investigation of new treatment paradigms informed by comprehensive genomic profiling of tumors."

"We utilized an RBPMS-NRG1 fusion cholangiocarcinoma PDX model that also contained mutations in both ERBB4 and IDH1," continued Dr. Odintsov. "While treatment with monotherapy seribantumab or afatinib in this model produced mixed results, by applying a triple combination of seribantumab with afatinib to target the entire ERBB family, and AG-120 to target the IDH1 mutation, we were able to achieve regressions in the majority of tumors. This suggests that tumors harboring multiple oncogenic drivers may benefit from combination therapy that addresses the contribution of each genomic alteration in disease progression."

In totality, the data reported support the use of monotherapy seribantumab to treat GI and other cancers that are uniquely driven by an NRG1 fusion in the ongoing Phase 2 CRESTONE study.