Cryptosporidiosis

Courtesy of Harold Cunningham/Getty Images Switzerland-based Novartis has had a very busy week, and it's not over yet. In addition to patent cases, partnerships and pledging money to global tropical disease efforts, the company scored a win on a combo-treatment for solid tumors. FDA Greenlights Two-Drug Combo for BRAF V600E Solid Tumors The U.S. Food and Drug Administration granted accelerated approval to Novartis’ Tafinlar (dabrafenib) plus Mekinist (trametinib) for treatment of adults and children six years and older with unresectable or metastatic solid tumors with a BRAF V600E mutation who have progressed after previous treatment and who have no satisfactory alternative treatment options. Because it is an accelerated approval, the company has to run confirmatory trials, or the approval could be rescinded. The combo is the first and only BRAF/MEK inhibitor approved with a tumor-agnostic indication for solid tumors with the BRAF V600E mutation. These mutations are associated with 20 different tumor types. “The combination of dabrafenib and trametinib demonstrated meaningful efficacy in multiple BRAF-positive tumor types, including in some patients with rare cancers who have no other treatment options available,” Dr. Vivek Subbiah, M.D., associate professor of Investigational Cancer Therapeutics and center medical director of the Clinical Center for Targeted Therapy, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center in Houston, Texas said. “Physicians should consider a BRAF test as a routine diagnostic step that could enable a new option for treating patients with many solid tumors.” Novartis Pledges $250 Million to Fight Tropical Diseases and Malaria The company endorsed the Kigali Declaration on neglected tropical diseases (NTDs) and pledged a five-year financial commitment of $250 million to fight NTDs and malaria with the Kigali Summit on Malaria and NTDs. This is along with the 26th Commonwealth Heads of Government (CHOGM) meeting. Novartis initially endorsed the London Declaration on NTDs in 2012, donating to global efforts to eliminate leprosy. The company committed $100 million in 2018 to fight malaria. The new investment will help to advance research and development of new therapeutics against NTDs and malaria. This includes $100 million to focus on four diseases, Chagas disease, visceral leishmaniasis, dengue fever and Cryptosporidium infection. “Over the past decade, great progress has been made against NTDs, but there is still a lot more work to be done,” Vas Narasimhan, chief executive officer of Novartis, said. “Novartis will continue progressing our longstanding commitment to helping realize a world free of NTDs. Today, by endorsing the Kigali Declaration and pledging to invest $250 million, we aim to accelerate progress toward elimination of these diseases, which continue to cause suffering and stigma for millions of people around the globe.” Last week, Novartis announced it was collaborating with PerkinElmer to expand newborn screening for sickle cell disease in sub-Saharan Africa. PerkinElmer and the Novartis Africa Sickle Cell Disease program will expand advocacy efforts to educate patients, caregivers and communities on how vital newborn screening and early intervention is with hydroxyurea (HU) and other SCD treatments. Novartis and Precision Unite on Sickle Cell and Thalassemia Gene Therapies Novartis and Precision BioSciences inked a partnership to develop a potential cure for hemoglobinopathies, including sickle cell disease and beta-thalassemia. Precision will create a custom ARCUS nuclease and conduct in vitro studies, then Novartis will take over the rest of the R&D, manufacturing and commercialization. Novartis will pay Precision $75 million upfront, but the deal includes up to $1.4 billion in potential milestones, additional research funding and tiered royalties on commercial products. Jay Bradner, president of the Novartis Institutes for Biomedical Research (NIBR), said, “We identify here a collaborative opportunity to imagine a unique therapeutic option for patients with hemoglobinopathies, such as sickle cell disease and beta thalassemia — a potential one-time treatment administered directly to the patient that would overcome many of the hurdles present today with other therapeutic technologies.” Novartis Loses MS Drug Patent Battle as Appeals Court Reverses Decision Yesterday, a U.S. Court of Appeals reversed its own 2020 ruling between Novartis and China’s HEC Pharm. The dispute was over Novartis’ multiple sclerosis drug Gilenya. The appeal focused on a specific no-loading-dose limitation in Novartis’ patent description of the drug, which the judges found to be in error. The court ruled in favor of Novartis in 2020, upholding the patient’s drug dosage regimen that prevented HEC and other generic drug companies from challenging the patent until Dec. 25, 2027. HEC filed an Abbreviated New Drug Application with the FDA with plans to produce a generic version of Gilenya before the patent expires in 2027. But the repeal cited experts claiming discrepancies in defining and interpreting the loading dose. Novartis expects to petition for further review of the dissolution. “Novartis intends to vigorously defend the validity of the patent and is considering all available options, including current plans to seek review of this decision by the full CAFC [U.S. Court of Appeals for the Federal Circuit], a process which may take several months,” Novartis stated.

Novartis has endorsed the Kigali Declaration on neglected tropical diseases (NTDs) by announcing a $250m investment over five years to fight against NTDs and malaria. The declaration aims to increase government support and secure commitments to achieve the SDG3 target on NTDs and to deliver the targets set out in the World Health Organization’s (WHO) Neglected Tropical Disease Roadmap. Country leaders, including presidents, community and business leaders, and philanthropists attended The Kigali Summit on Malaria and NTDs to renew high-level commitments and to galvanise action to end these diseases. $100m of the investment will be used to advance research and development of Novartis’ NTD programme, that includes Chagas disease, leishmaniasis, dengue and cryptosporidiosis. The other $150m will be used to advance the clinical development programmes of its three novel drug candidates to combat the emerging resistance to malaria treatment artemisinin and develop a new formula for babies under 5kg with malaria. 1.7 billion people around the world are affected by NTDs, which are prevalent in tropical areas and mostly affect impoverished communities, causing devastating health, social and economic consequences. According to the 2021 World Malaria Report, there were 241 million cases of malaria and 627,000 malaria deaths in 2020. Children under five are particularly at risk, with malaria taking the life of a child every minute in Africa. Novartis, working with partners, has delivered more than one billion treatments for malaria to date, including more than 450 million paediatric treatments, without profit to malaria-endemic countries. Van Narasimhan, CEO of Novartis, said: “Over the past decade, great progress has been made against NTDs, but there is still a lot more work to be done. Novartis will continue progressing our longstanding commitment to helping realise a world free of NTDs. “Today, by endorsing the Kigali Declaration and pledging to invest $250m, we aim to accelerate progress toward elimination of these diseases, which continue to cause suffering and stigma for millions of people around the globe.” Novartis was among the original endorsers of the London Declaration on NTDs in 2012, committing to a multidrug therapy (MDT) donation to support global efforts to eliminate leprosy. A subsequent commitment of $100m was made in 2018 towards the fight against malaria.

Over the next five years, Novartis is pledging to pour $250 million into R&D for new treatments of neglected tropical diseases and malaria — with the ultimate goal of eliminating these diseases. “Over the past decade, great progress has been made against NTDs, but there is still a lot more work to be done,” CEO Vas Narasimhan said in a statement. About 1.7 billion people still suffer from NTDs around the world, mostly in impoverished areas, and while malaria doesn’t fall in the NTD category, it still affects 241 million people and kills hundreds of thousands of children every year. Specifically, Novartis is allocating $100 million toward four NTDs. The Novartis Institute for Tropical Diseases will be leading up the work, which spans anti-parasitic therapies for Chagas disease (in collaboration with Wellcome), a Phase II-ready candidate to treat visceral leishmaniasis, a Phase I drug for dengue fever and a Phase I program tackling cryptosporidium infection. As for the $150 million malaria initiative, Novartis wants to focus on three drug candidates that promise to combat the emerging resistance to artemisinin, while also supporting the development of optimized formulation for neonates and infants under 5 kg. Novartis has previously committed $100 million toward malaria eradication in 2018 and donated a number of its therapies over the years, including the parasitic flatworm treatment Egaten and a multidrug therapy for leprosy. It’s also been rewarded with tropical disease priority review vouchers for some of those treatments, stoking controversy among global health advocates.