Why UniQure's Etranacogene dezaparvovec Gene Therapy Still Holds A Promise For Hemophilia B Patients With Unmet Medical Needs
If you are hemophilia patients, scientists, or investors, you must have heard about the gene UniQure's (Nasdaq: QURE) Etranacogene dezaparvovec gene therapy program for the treatment of Hemophilia B. One subject in the HOPE-B clinical trial was diagnosed with Hepatocellular carcinoma, a form of liver cancer. This incident has generated a flurry of news and pessimism about the future of the gene therapy program and UniQure company. The stock was down 10 to 15% with emotional sell-offs from investors. I will tell you three reasons why UniQure still holds a promise to deliver gene therapy for Hemophilia B patients and everyone needs to take a deep breath and show patience. 
Three Reason Why Etranacogene dezaparvovec Gene Therapy Still Holds A Promise.
Adeno-associated Virus Plaform
Uniqure's Hemophilia B Gene Therapy Program utilizes Adeno-Associated Virus Serotype 5 (AAV5) to deliver the gene that encodes a functional copy of Factor IX variant (Padua) into the liver tissues. These AAV5 are genetically modified to inactivate the viral self-replication, reduce the integration of the viral genome into the host DNA. The genetically modified AAV5 has been used in other clinical programs from UniQure and other companies like Biomarin. Any cancer incidence or development has not been observed in any AAV5 gene therapy clinical programs for over ten years.
Hemophilia B Clinical Program
The HOPE-B, a phase 3 clinical trial, enrolled 54 subjects with severe hemophilia, with additional participation in phase 2 studies. In both of these clinical studies, the subjected were administered Etranacogene dezaparvovec, and none of the subjects have shown to develop hepatocellular carcinoma or cancer of any form, except this specific subject. While it is not impossible but it is less likely that Etranacogene dezaparvovec has caused hepatocellular carcinoma in this subject.
Subject that developed hepatocellular carcinoma had predisposing conditions
Based on the information provided by UniQure, this specific subject from the HOPE-B clinical trial had predisposing conditions including chronic hepatitis C infection and hepatitis B infection. Both of these chronic hepatic infections are the known predisposing factors with higher odds for developing hepatocellular carcinoma. With these facts in hand, it is more likely that these predisposing factors may have been associated with the HCC.
How about the hold on the clinical program?
I believe the FDA has taken action to hold this clinical program to ensure the safety of the subjects and out of precautionary measures. The enrollment for the pivotal HOPE-B clinical program is already been completed. This FDA action pauses any other actively recruiting clinical programs for Etranacogene dezaparvovec. Now, it is imperative to show that the hepatocellular is not associated with the Etranacogene dezaparvovec infusion.
The FDA may enforces the clinical screening of all the remaining subjects from clinical studies and also the development/implementation of the robust biomarker for early detection of these carcinomas. The investigations that may also include
a) Evaluation of integration of Etranacogene dezaparvovec into the liver
b) Evaluation of site of integration, and whether it activated factors (oncogenes) that causes hepatocellular carcinoma
c) Evaluation of host factors that may have caused the development of hepatocellular carcinoma
What is the future of Etranacogene dezaparvovec?
It is astonishing to learn the advancement of gene therapies have enabled disease-altering treatment for these genetic disorders. This particular event has also revealed there are still unanswered questions that need to be addressed. And, I strongly believe that UniQure's Etranacogene dezaparvovec is the front runner to deliver this disease altering treatment for Hemophilia B patients. It will reach the finish line and benefit Hemophilia B patients with unmet medical needs.