The FDA has just recently approved CYRAMZA as a treatment for those with hepatocellular carcinoma (HCC), who have been treated with sorafenib, and who have ≥400 ng/mL of alpha-fetoprotein (AFP). Until now, there had been no approved therapy specifically made for those living with that high a level of AFP. This form of HCC is often more aggressive and the prognosis is even worse than normal.
Additionally, and thankfully, the FDA has also announced that they have removed their boxed warning from the drug.
HCC is unfortunately the fastest growing cause of cancer death in the United States. The incidence of this disease is continually rising. This is due to obesity/fatty liver disease, diabetes, under-diagnosis of chronic liver disease, lack of access to therapy for viral hepatitis, or continued cancer risk even after viral hepatitis is treated.
For those patients who have high levels of AFP, without treatment, survival is only 3-5 months post diagnosis.
Current treatment options for the disease are not adequate and the more liver damage there is, the fewer options a patient has. For instance, for advanced stage patients, surgery is typically not an option.
The one good thing about AFP is that its levels can be assessed through a blood test. This allows doctors to monitor the progression of disease easily as well as select patients who may respond best to various therapies.
CYRAMZA, by itself or as a combination therapy, is currently being investigated in over 110 different clinical trials across the world. In total, these trials have enrolled over 15,000 individuals.
CYRAMZA is a VEGF Receptor 2 antagonist. It binds to VEGFR-2 and blocks the receptor ligands from binding. This can slow the growth of tumors. In an animal model, it was able to prevent angiogenesis.
What was the boxed warning for you may be wondering? The warning discussed the danger of gastrointestinal perforation, impaired wound healing, and hemorrhage. These risks are still included in the package so that physicians and patients can ensure they are making the right treatment decision.
Phase 3 Trial
CYRAMZA’s most recent approval was based on a Phase 3 clinical trial titled REACH-2. (The REACH study was the investigation that first uncovered AFP as a usable biomarker in this disease). REACH-2 was a double-blind and randomized trial comparing the drug to placebo in HCC patients who were AFP-high and had been treated with the drug sorafenib.
The primary endpoint of the trial was overall survival. The secondary endpoint was progression-free survival. CYRAMZA was statistically significant for both of these endpoints. Eli Lilly and Company, the developer of this drug, has already filed for marketing authorization of CYRAMZA in both Japan and the EU. Action is expected by mid-2019.
In addition to this good news, Lilly has also recently announced positive results from their Phase 3 investigation of the drug as a treatment for EGFR-mutated metastatic non-small cell lung cancer. The company plans to file for approval by mid-2019.
This recent approval of CYRAMZA is a milestone for this HCC patient population and another noteworthy contribution to the field of precision medicine. This approval is for a very unique and rare group of patients living with an advanced form of disease. With this approval, these patients have a new source of hope.
You can read more about this new approval for CYRAMZA here.