Despite advances in bone marrow transplants over the last 30 years, CMV remains one of the
leading causes of death in the first year following a transplant. Moreover, adenovirus can be rapidly fatal in immunocompromised patients with disseminated disease. There are no medicines approved to prevent CMV or treat adenovirus in hematopoietic cell transplant (HCT) recipients.
In addition to commercializing novel, oral antivirals for areas of high unmet medical need, we’re working with the Biomedical Advanced Research and Development Authority (BARDA) to develop a medical countermeasure to treat smallpox in the event of a bioterror attack or accidental release.
Our proprietary lipid conjugate technology platform—which leverages lipid side-chains, such as nucleotides, to enhance antiviral bioavailability—enables us to drive therapy development for these viral infections and beyond.
A common barrier to finding effective therapies is the lack of molecules that can be given orally due to poor absorption in the gut or poor tissue penetration.
Our proprietary lipid technology directly addresses this barrier by attaching lipid side-chains to antivirals, such as nucleotides, that are limited by poor gut absorption. These lipid-antiviral conjugates are thought to mimic a phospholipid in the cell membrane and thus use the natural uptake pathways in the small intestine to achieve oral bioavailability and efficient tissue penetration. It is thought that the lipid side-chain facilitates efficient uptake into the target cells as evidenced by much higher concentrations of the active antiviral measured in the cell in vitro.
Two Chimerix lipid-nucleotide conjugates are currently in clinical development: brincidofovir (BCV, CMX001) and CMX157. A third conjugate, CMX669, is currently in discovery phase.
Our lead product candidate, brincidofovir, is a clinical-stage nucleotide analog that has shown in vitro antiviral activity against all five families of DNA viruses that affect humans, including cytomegalovirus (CMV), adenovirus, BK virus and herpes simplex viruses.
Brincidofovir and Transplant Patients
There are no approved therapies for the prevention of CMV in hematopoietic cell transplant (HCT, or bone marrow transplant) recipients. Available antivirals are associated with known toxicities, such as bone marrow suppression and renal impairment. But significant morbidity (diseased state) and mortality (death) are associated with CMV and other viral infections in the first year post transplant. A mortality rate (death rate) of approximately 1 in 5 patients during the first year following HCT is independent of mortality from relapse of the underlying disease. This 20% non-relapse death rate is caused by post-transplant complications—including viral infections like CMV in particular—as well as bacterial and fungal infections and graft failure.
Approximately 20,000 hematopoietic transplants are performed annually in the U.S., and a similar number in Europe - representing a great unmet need for effective therapies that help protect immunocompromised patients.8
With no preventive therapy approved for CMV in HCT recipients, Chimerix is committed to moving brincidofovir forward in this indication. Plans for brincidofovir in HCT recipients will be the subject of further discussions with the FDA and other regulators.
Chimerix also plans to pursue Phase 2 trials of brincidofovir in kidney transplant recipients to confirm activity against BK virus and to determine the safety profile of brincidofovir in this population.
Brincidofovir and Adenovirus
Currently, there are no therapies approved for the treatment of adenovirus. Disseminated adenovirus disease can be associated with a mortality rate of up to 80% in patients who are undergoing hematopoietic cell transplant (HCT, also called bone marrow transplant).6
In 2015, Chimerix completed enrollment of its AdVise Study, which is evaluating brincidofovir for the treatment of adenovirus infections in pediatric and adult patients. The company is also conducting Study 305 to obtain clinical outcomes data in patients considered matched controls from the same medical centers as AdVise participants.
Chimerix is currently enrolling patients in Study 351 to provide patients with serious adenovirus infection or disease access to treatment with brincidofovir.
for trial information.
Brincidofovir for Smallpox
In 2011, Chimerix received a grant of $81 million from the Biomedical Advanced Research and Development Authority (BARDA) to continue exploring the development of brincidofovir (CMX001) as a medical countermeasure to treat potential smallpox outbreaks in the event of a bioterror attack or accidental release. If successful, brincidofovir could be an important contribution to U.S. national security and public health preparedness for the treatment of smallpox—a virus for which there is no approved treatment.
In 2014, Chimerix was awarded a contract extension from BARDA of $17.0 million to further support the development of brincidofovir, and in September 2015 received a second contract extension of $13.0 million for a period of 15 months. Read more