Improving outcomes for immunocompromised patients
Chimerix, a biopharmaceutical company in Durham, North Carolina, is developing innovative medicines to prevent and treat multiple, life-threatening viral infections in bone marrow transplant recipients and other people with weakened immune systems.
Approximately 81,000 hematopoietic cell transplants (HCTs; also known as bone marrow or stem cell transplants) are performed each year worldwide. Nearly two-thirds of HCT recipients experience two or more infections with DNA viruses, most commonly adenoviruses (AdVs), BK virus, cytomegalovirus (CMV), and other human herpes viruses. Infection with multiple viruses increases the risk of prolonged or repeated hospitalizations, illness, and death in the first year after transplant. Combined infectious causes remain a significant factor contributing to the 1-in-5 mortality rate in the first year after HCT, which leads approximately half of the people who are offered this potentially curative procedure to decide not to undergo the transplant. Currently, there are no approved medicines for the treatment of AdV or for preventing infection by CMV and other DNA viruses in HCT recipients.
Chimerix is on a mission to address this problem by discovering, developing, and commercializing much-needed medicines that can improve outcomes for immunocompromised patients. Incorporated in 2000, the biopharmaceutical company has developed a proprietary lipid-conjugate technology that has led to two promising clinical-stage product candidates: brincidofovir (CMX001) and CMX157.
Chimerix’s lead candidate, brincidofovir, has demonstrated broad-spectrum antiviral activity against DNA viruses that affect humans, including AdVs, herpes viruses such as CMV, BK virus, and smallpox. CMX157 is licensed to ContraVir Pharmaceuticals and is in development for the treatment of hepatitis B virus and HIV. Chimerix also recently announced a new clinical candidate, CMX521, which is being investigated for the treatment and/or prevention of norovirus.
Chimerix is committed to discovering, developing, and commercializing medicines that improve outcomes for immunocompromised patients.
“Our goal is to develop safe and effective therapies to protect immunocompromised patients from life-threatening infections so they can remain on the path to recovery,” said Chimerix’s president and CEO, M. Michelle Berrey.
Improving drug delivery
A common problem in drug development is that many potentially effective treatments cannot be given orally owing to poor absorption in the gut or poor tissue penetration. Chimerix’s innovative lipid-conjugate technology overcomes this problem through the attachment of lipid side chains to antivirals, such as nucleotides. These lipid–antiviral conjugates are thought to facilitate absorption of the compound across the gut and into the bloodstream, and deliver it to the cells where viral replication occurs, while also helping to address some unwanted side effects of currently available medicines.
“We welcome opportunities to explore collaborations that could result in the discovery, development, or commercialization of other new orally available molecules,” Berrey said.
Leading the way with brincidofovir
Chimerix’s lead product candidate is a nucleotide-analog lipid conjugate that has shown broad-spectrum antiviral activity, with a high barrier to drug resistance, no toxicity to the bone marrow, and low risk of kidney toxicity. Brincidofovir has received Fast Track designation from the US Food and Drug Administration for the treatment of AdV, smallpox, and CMV. The promising product candidate has also received Orphan Medicinal Product designation from the European Commission for the treatment of AdV and prevention of CMV disease, and the Committee for Orphan Medicinal Products has issued a positive opinion for an Orphan Designation for the drug for the treatment of smallpox.
Chimerix is planning to conduct a new study, AdAPT (Adenovirus after Allogeneic Pediatric Transplantation), to further evaluate the efficacy of a short course of oral brincidofovir in treating AdV infections after pediatric HCT. Additionally, the company has developed an intravenous formulation of brincidofovir that is now in human trials. Chimerix is planning phase 2/3 studies to evaluate intravenous brincidofovir for the prevention of AdV and other DNA viral infections in allogeneic patients who have undergone stem cell transplant, and for the treatment of CMV and BK virus infections in transplant recipients and other patient populations.
Chimerix is working with the Biomedical Advanced Research and Development Authority within the US Department of Health and Human Services to develop brincidofovir as a medical countermeasure for the treatment of potential smallpox outbreaks caused by accidental release or deliberate dispersal as part of a bioterror event. “If successful, brincidofovir could be an important contribution to US national security and public health preparedness for the treatment of smallpox—a virus for which there is no approved treatment,” Berrey said. “Given the global risks of infectious bioweapons, we believe that other countries would also be interested in securing brincidofovir for smallpox outbreaks, should our trials be successful.”
Chimerix is also conducting targeted screening of its rich chemical library to build other, more potent antivirals. This library contains a diverse array of heterocyclic ring-system molecules, including more than 3,000 structurally diverse nucleoside derivatives.
The company actively seeks collaborations with the aim of augmenting its discovery programs and development pipeline. Areas of interest include stem cell transplantation, solid organ transplantation, specialty/critical care infectious diseases, hematology– oncology, and antifungals. “Chimerix has a strong commitment to pursuing collaborations that will result in improvements in patient care,” Berrey said. “We see significant opportunities for expansion into diseases that have major global impact and for which there are currently no effective treatments.”
Linda M. Richardson, Chief Strategy and
Durham, North Carolina, USA