DNA delivery technology (Vical) and rAAV Vctor Technology (Targeted Genetics)

VICAL’S DNA DELIVERY TECHNOLOGY

Vical (VICL) had licensed its its DNA delivery technology to the Japanese firm AnGes MG. This firm reported positive results on its drug candidate developed based on Viccal’s technology. The drug, HGF genetic uses Vical’s technology to deliver a gene encoding Hepatocyte Growth Factor (HGF), a human protein that causes angiogenesis (growth of blood vessels) in areas of ischemia (restricted blood flow).

Interim analysis of data from a Phase 3 trial on patients with critical limb ischemia (advanced peripheral arterial disease) demonstrate that the drug is safe and has achieved statistical significance with regard efficacy. As a result, an Independent Data Monitoring Committee (IDMC) recommended stopping the trial early to prevent potential ethical issues against the placebo group subjects. AnGes is ending the trial and preparing to file an application for Japanese marketing approval.

The results validate Vical’s DNA delivery technology.

TARGETED GENETICS’ rAAV VECTOR TECHNOLOGY

TARGETED GENETICS (TGEN’S) inflammatory arthritis drug tgAAC94 is a TNF modulator developed for intra-articular injection. The rationale behind this drug development is based on the fact that not all arthritis patients fully respond the approved systemic tumor necrosis factor-alpha (TNF-alpha) antagonists, which otherwise were tremendously effective in stopping the joint inflammation and progressive degeneration.

Obviously, Targeted Genetics drug tgAAC94 attempts to benefit those patients who have not been lucky with the systemically administered anti-TNF drugs such as Enbrel and Remicade. What encouraged Targeted Genetics to develop the drug is its recombinant (rAAV) vector technology, which made possible the development of an effective intra-articular TNF inhibitor version. The drug was tested in clinical trials and recently, some results began to emerge, suggesting good news.

Results: Data from the dose escalation arm of the ongoing Phase 1/2 clinical study of tgAAC94 on patients with inflammatory arthritis demonstrate that tgAAC94 is safe and provides clinical benefit to arthritis patients who are being treated with the marketed systemic TNF antagonists. At week 12 after treatment with tgAAC94, 13%, 14% and 33% of subjects receiving low, mid and high dose tgAAC94, respectively, achieved a two-point reduction in swelling compared to none who took placebo. A trend towards reduction of swelling was observed in tgAAC94-injected joints compared to placebo in subjects with or without concurrent use of systemic TNF antagonist.

According to the firm’s scientists, the data suggest that tgAAC94 has helped arthritis patients who have not fully benefited from the systemic TNF antagonists.

Targeted Genetics promised to present additional data that provide more insight into the most effective way to advance the development of tgAAC94. Further testing is currently being made with a follow up that enables further assessment of safety, improvement in swelling and functional improvement in the treated joints. MRI is planned on treated joints in a subset of subjects for image-based assessment.

Comments: Taking care of patients who do not benefit from the best arthritis treatments in town is necessary if feasible. It seems it is. The beneficial effect, if confirmed would touch the patients, the rheumatologists and Targeted Genetics. It validates its technology.

Like the firm, we are also encouraged by the results of Phase 1/2 trials and are anxious to learn more from the additional data that will be presented soon. If tgAAC94 passes the test, it will be a great validater of Targeted Genetics’ rAAV vector technology, which is used to deliver a DNA sequence that encodes a soluble form of the TNF-alpha receptor (TNFR:Fc).

This technology was originally developed to deliver genes for gene replacement. The concept proved to be working as the rAAV vector technology enabled the lintraarticularly injected tgAAC94 to instigate an intracellular secretion of TNFR:Fc within joints, preventing TNF alpha from causing joint inflammation and destruction. Adeno-associated virus (AAV) has never been associated with any disease in humans.

It is another validation of a relevant, but difficult technology that has taken a long time to provide results. We hope the results will be confirmed.