- web-based article
- Matthew Dennis
Introgen Therapeutics has submitted a BLA to the FDA, while simultaneously Gendux Molecular (Introgen) has submitted an MAA to the EMEA, both seeking marketing approval for Advexin (INGN 201), the company’s targeted p53 tumour suppressor gene therapy, to treat recurrent, refractory head and neck cancer. INGN 201 represents the first in a new class of tumour suppressor cancer therapy and is the first of its kind to be submitted for regulatory approval in the US and Europe. Introgen has requested priority review from the FDA for INGN 201, meaning that the treatment could be on the market in early 2009.
INGN 201 therapy harnesses the body’s natural tumour suppression mechanisms to fight cancer, without the toxicities associated with conventional cancer treatments. Abnormalities in protective tumour suppressor p53 pathways are associated with the majority of all solid cancers. Designed to restore patients’ ability to fight cancer, INGN 201 delivers large doses of the normal p53 gene to target abnormal p53 function present in tumour cells, which triggers natural tumour suppression mechanisms in cancer without harming normal cells.
According to Dr Jack Roth, inventor of Advexin and professor at the University of Texas MD Anderson Cancer Center: “This is an important milestone in the clinical application of gene therapy for cancer patients. With the use of p53 biomarkers, Advexin will provide more effective and less toxic treatment for head and neck cancer patients who have limited treatment options.”
The submissions are based on pivotal Phase II and III trials evaluating survival, tumour response and safety in patients with recurrent, refractory end-stage, squamous cell carcinoma of the H&N. These studies incorporated common diagnostic tests to identify patients most likely to benefit from INGN 201 based upon pretreatment tissue analyses to determine p53 profile status.
The Phase III trial achieved the study’s objectives and demonstrated clinical benefit of INGN 201 in comparison to the control drug, methotrexate. The patients most likely to benefit from INGN 201 treatment with increased tumour responses and survival were identified by prespecified p53 biomarker profiles. Overall, the study results demonstrated that INGN 201 addresses an unmet medical need and the combination of biomarker testing and treatment has the potential to provide recurrent H&N cancer patients with an effective therapy that is less toxic than standard chemotherapies.
INGN 201 is Advexin’s lead product candidate, approval of which may open the door for the company’s other gene therapy drugs. Indeed, INGN 201 is being investigated in Phase II trials for breast, non-small cell lung and oesophageal cancer, as well as earlier-stage studies in prostate, ovarian, bladder, brain and bronchoalveolar cancer. However, it is unclear whether regulatory bodies will even approve INGN 201. The FDA has faced considerable scrutiny in recent years for approving drugs that have turned out to produce dangerous side effects, and it has become more cautious as a result. How the Agency along with the EMEA will view the first in a new class of drugs remains to be seen.
1. Matthew Dennis – Editor, Cancer Drug News