Multi-Centric Castleman's Disease

Sanofi’s Enjaymo, the only approved drug therapy for a rare and debilitating blood disorder, is being acquired by Recordati in a deal that helps the Italian company build its rare disease portfolio and expand its commercial reach in key markets. Recordati is paying $825 million up front for global rights to Enjaymo, a drug that is approved in the U.S., Japan, and Europe. If the drug achieves sales milestones, the company could pay out up to $275 million more, according to deal terms announced Friday. Sanofi and Recordati expect to complete the transaction by the end of this year. Enjaymo treats cold agglutinin disease, a condition in which the immune system attacks red blood cells and causes them to rupture. This process happens at cold temperatures, giving the disease its name. At these temperatures, antibodies that normally attack bacteria instead attach to red blood cells, causing them to bind together, or agglutinate. The red blood cells are destroyed by the immune system, leading to anemia. presented by Health Tech What’s Keeping Healthcare CIOs Up at Night: How to Improve Patient Satisfaction by Handling Calls More Efficiently Health systems have spent billions on portals while investments in modernizing the voice channel — the dominant preference of healthcare consumers — have taken a backseat. By Stephanie Baum The resulting anemia can be managed with blood transfusions. Enjaymo takes a different approach by interfering with the process that leads to red blood cell destruction in cold agglutin disease. The drug, an intravenously infused monoclonal antibody, is designed to selectively target and block a complement system protein called C1. This in turn stops immune system antibodies from attaching to immune cells. The FDA approved Enjaymo in 2022. Approvals in Japan and Europe soon followed. In these three markets, the companies estimate cold agglutin disease affects between 11,000 and 12,000 patients. Recordati, which is headquartered in Milan, is the latest stop in a long journey for Enjaymo. The drug was initially developed by True North Therapeutics, which itself was acquired by Bioverativ in 2017. In 2018, Sanofi paid $11.6 billion to buy Bioverativ. Enjaymo generated €72 million (about $79 million) in sales last year, a 240% increase over the product’s sales in 2022, according to Sanofi’s annual report. Sales for Enjaymo are continuing to grow, but it’s not on track to become a blockbuster seller. Recordati said that in the 12 months ending in August, the drug accounted for €100 million (about $109 million) in revenue. The company projects the product’s peak sales could reach €250 million to €300 million (about $274 million to $328 million). Recordati said its milestone payment to Sanofi is tied to the achievement of net sales at or above the top end of peak year sales expectations. Rare disease accounts for about 34% of Recordati’s more than €2 billion in annual revenue, according to a September investor presentation. Most of those rare disease sales are in the U.S. Much of the company’s rare disease portfolio is comprised of assets from its 2022 acquisition of EUSA Pharma, a developer of drugs for rare cancers. Sponsored Post Get Ready for HLTH 2024: A Preview Guide HLTH 2024, scheduled for October 20-23 at the Venetian Expo Center in Las Vegas, will highlight new programming, a physicians roundtable, generative AI, the shifting landscapes of telemedicine, retail health, women's health, and lots more. By Stephanie Baum In a prepared statement, Recordati CEO Rob Koremans said Enjaymo is particularly complementary to one of those products, Sylvant. This drug, an antibody designed to block the inflammatory signaling protein IL-6, has approvals in more than 40 countries for treating idiopathic multicentric Castleman disease, a rare disorder characterized by abnormal growth of the lymph nodes. While this disease is not cancer, its progression is similar to that of lymphoma, a cancer of the lymph nodes. Last year, Recordati began exploring the development of Sylvant for other diseases driven by IL-6 signaling. “Enjaymo further expands our rare diseases footprint in the U.S., Japan and Europe, and will contribute positively to both our top and bottom lines,” Koremans said. “Most importantly, with a strong clinical profile and as the only product approved for the treatment of [cold agglutinin disease], Enjaymo addresses a serious unmet medical need for patients living with this debilitating disease.” Image by istocksdaily, via Getty Images

Researchers have developed a model of Kaposi sarcoma that could expedite the development of new drugs to treat the disease, which is the most common cancer in people living with HIV. Researchers at UNC Lineberger Comprehensive Cancer Center, after decades of research efforts, have developed a mouse model of Kaposi sarcoma that could be key to the development of new drugs to treat the disease. Kaposi sarcoma is a cancer that is the most common cancer in people living with HIV. The findings appeared in Cell Host & Microbe. "This is an important development as we have created the first animal model ever of Kaposi sarcoma. Animal models are essential to move new drugs from the laboratory bench into clinical trials," said UNC Lineberger's Dirk Dittmer, PhD, senior corresponding author, co-leader of the UNC Lineberger Virology Research Program and director of the UNC Viral Genomics Core. "Before this, only repurposed drugs from other cancers were used to treat Kaposi sarcoma, but now we can start investigating entirely new compounds to help treat what can be a lethal cancer." About 20% of all human cancers arise from viruses or require viral infection as an essential cofactor. The Kaposi sarcoma-associated herpes virus (KSHV) was discovered in 1994 and is associated with Kaposi's sarcoma as well as B-cell cancers. KSHV-associated diseases affect internal organs and are ultimately fatal. In the U.S., the diseases are found primarily in immunosuppressed people such as those who are HIV-positive or are transplant patients. Worldwide, an estimated 34,270 cases of Kaposi sarcoma were diagnosed, and 15,086 deaths reported in 2020, with twice as many cases and deaths occurring in men compared to women. Africa accounted for 73% of new cases and 86.6% of the deaths from Kaposi sarcoma worldwide. The disease is endemic, and not HIV-related, in some southern and eastern African countries. Aside from animal models, one way to study cancer is to look at tumor cells in the lab. But according to Dittmer, Kaposi sarcoma tumor cells are very finicky and dependent on signaling molecules and blood supply, which is why they don't survive in a laboratory culture dish. Therefore, researchers have been focusing on developing animal models that would mimic, as closely as possible, the disease in humans. One of the challenges the researchers faced in developing their model was the fact that two types of genes are transcribed into proteins in the Kaposi sarcoma mouse model. Normally when a virus infects a cell, the cell dies as the virus replicates, which is a process called cell lysis; the genes that are needed for the virus to propagate itself are lytic genes. Cancer viruses are different as they enter a quiet state, called latency, where only the genes that help the infected cell survive are expressed. The mouse model the researchers developed is complex as a bit of both types of genes were needed. Cervical cancer and its related virus, HPV (human papilloma virus), offers a good comparison for the challenge of developing a Kaposi sarcoma mouse model. The KSHV genome is 20 times larger than HPV. HPV has two cancer-causing genes, E6 and E7, so to mimic the disease in animals, researchers only needed to design two mice, one for each gene. KSHV may have as many as 10 cancer-causing genes that all work together so it would be way too difficult to develop that many mice, hence the virtue of their single model, Dittmer noted. "Another of the key virtues of our new mouse model is that it helps us understand angiogenesis, or new blood vessel formation. Without angiogenesis cancer cells are deprived of oxygen and die," Dittmer said. "In this mouse model, we can study angiogenesis blocking drugs better than ever before. If new drugs work against Kaposi sarcoma, they will also likely work against lesser-angiogenic tumors, which would be a major plus." For next steps, the researchers hope that others will pursue drug and vaccine development based on a new understanding of fundamental aspects of KSHV provided by their mouse model, including possible development of a much-needed primate model for human KSHV and Kaposi sarcoma.

Researchers have discovered a key mechanism used by Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8), to induce cancer. The research points to effective new treatment options for KSHV-associated cancers, including Kaposi's sarcoma, primary effusion lymphoma, and HHV8-associated multicentric Castleman disease. Cleveland Clinic researchers have discovered a key mechanism used by Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8), to induce cancer. The research points to effective new treatment options for KSHV-associated cancers, including Kaposi's sarcoma, primary effusion lymphoma, and HHV8-associated multicentric Castleman disease. "Our findings have significant implications: viruses cause between 10% to 20% of cancers worldwide, a number that is constantly increasing as new discoveries are made. Treating virus-induced cancers with standard cancer therapies can help shrink tumors that are already there, but it doesn't fix the underlying problem of the virus," said Jun Zhao, Ph.D., of Cleveland Clinic Florida Research & Innovation Center. "Understanding how pathogens transform a healthy cell into a cancer cell uncovers exploitable vulnerabilities and allows us to make and repurpose existing drugs that can effectively treat virus-associated malignancies." The Nature Communicationsstudy, led by Dr. Zhao, reveals that KSHV manipulates two human enzymes called CDK6 and CAD to reshape the way human cells produce new nucleotides -- the building blocks of DNA and RNA -- and process glucose. The changes to how infected cells grow and how KSHV persists put cells at a much higher risk of forming tumors and play a crucial role in causing cancer. The team showed the virus activates a specific pathway driving cell metabolism and proliferation. Inhibiting this process with existing FDA-approved breast cancer drugs reduced KSHV replication, blocked lymphoma progression and shrunk existing tumors in preclinical models. Like other herpesviruses, KSHV often has no symptoms initially and remains in the body after primary infection. The virus stays dormant, suppressed by the immune system. However, KSHV can reactivate when immunity is weakened -- as in older people, those with HIV/AIDS, and transplant recipients. In these high-risk groups, the now active virus can trigger aggressive cancers. KSHV-induced cancers are fast-acting, aggressive and difficult to treat. An estimated 10% of people in North America and Northern Europe have KSHV, but this ranges throughout the globe. More than 50% of individuals in parts of Northen Africa are estimated to have the virus. Experts estimate these rates are higher, as KSHV often goes undiagnosed because of lack of symptoms. These findings have implications that reach past KSHV; researchers can apply knowledge about KSHV to other cancer-associated viruses that might use the same process to cause cancer. To understand the cells' metabolic processes to uncover the virus's vulnerabilities, Dr. Zhao collaborated with Michaela Gack, Ph.D., Scientific Director of the Florida Research & Innovation Center. Rapidly replicating cancer cells reprogram metabolism to fuel growth. Meanwhile, most viruses cannot produce energy or necessary molecules on their own, so they rely on human cells to do the work for them. The team found that the virus takes over the host protein CDK6 and CAD, causing the infected cells to produce extra metabolites, which allows faster replication of the virus and an uncontrolled proliferation of the cells. The research team treated pre-clinical models with a CDK6-blocking drug, Palbociclib, an FDA-approved breast cancer medication, as well as a compound targeting CAD. They saw significant decreases in tumor size and increases in cancer survival rates: most tumors virtually disappeared after about a month of treatment, and remaining tumors shrank around 80%. Survival increased to 100% for selected lymphoma cell lines. Dr. Zhao and his team are working to better understand the connections among KSHV, CDK6/CAD pathway, and cancer formation. With the knowledge they obtain, they plan to implement and refine their experimental drug combinations for clinical trials. "Cellular metabolism could be hijacked by both viruses and cancers for pathogenesis," said Dr. Zhao. "By investigating these metabolic rewiring mechanisms, we aim to find the Achilles' heel of cancer-causing viruses and non-viral cancers. I'm excited to see what the future of this work holds."