NeurogesX part II
Last time I covered the therapeutic market area of neuropathic pain, which is Neurogesx’ major area of focus. This time I’ll be doing the due diligence on their first product candidate NGX-4010, and it’s safe to say that the entire company rests with the fate of this therapeutic. NGX-4010 is a non-narcotic analgesic formulated in a topical (transdermal) patch containing an 8% concentration of synthetic capsaicin. Capsaicin is released from the patch and absorbed into the skin without significant absorption into the bloodstream. The chemical capsaicin is popularly known as the compound which gives hot chili peppers their spicy properties and natural concentrations range from 0.1% to 1% w/w. Chemically known as trans-8-methyl-N-vanillyl-6-nonenamide, it is a highly selective agonist for the transient receptor potential vanilloid receptor 1 (TRPV1). TRPV1 is a ligand-gated, nonselective, cation channel preferentially expressed in nociceptive sensory nerves. TRPV1 responds to noxious stimuli, including capsaicin, heat, and extracellular acidification, and integrates simultaneous exposures to these stimuli.
Low doses of capsaicin cream have long been used successfully for relief of neuropathic pain. However the first published study to use high doses (5-10%) in combination with regional anesthesia (to numb the normal burning sensation accompanying such high dose) was published in 1998 from UCSF. This study showed that at these levels of capsaicin, 90% of patients (N=10) were relieved from neuropathic pain from 1 to 18 weeks. Interestingly, in 1996, prior to the publication three of the authors of the study patented the use of high percentage capsaicin with the Regents of the
So Neurogesx has the worldwide exclusive license for a high concentration capsaicin transdermal patch. The use of high-concentration capsaicin itself is not exactly in the public domain but neither does NGSX have exclusive worldwide rights. Therefore, it goes without saying any investment in Neurogesx is banking on the utility of the transdermal patch method of capsaicin delivery. As it turns out the only current alternatives to a transdermal patches are a topical creams which of course have the drawback of wildly inaccurate dosing (FDA wont approve) and injection such as Anesiva is developing for post surgical pain.
Now that we’ve covered the therapeutic market and the intellectual property let’s move on to the pipeline. NGX-4010 has completed two phase 3 clinical trials that have met their primary endpoints, one in PHN and one in HIV-DSP. The results demonstrated that a single 30 or 60 minute application of NGX-4010, depending on the indication, may provide at least 12 weeks of clinically-meaningful pain relief. Neurogesx expects to file a marketing authorization application in Europe for NGX-4010 in 2007 based upon existing clinical trial data, and if the safety and efficacy of NGX-4010 are confirmed by two ongoing pivotal Phase 3 clinical trials, they intend to file a new drug application in the
Relatively speaking, I feel that the Neurogesx story is fairly straightforward for a biotech company. First, the therapeutic market is underserved in terms of an easily administered, but long lasting, transdermal patch. Secondly, the intellectual property situation is not ideal but NGSX has 30% of the license for high-concentration capsaicin and a monopoly on the patch delivery. Finally we are looking at a late stage development pharmaceutical which needs secondary phase 3 studies before filing the NDA. That being said, the elephant in the room here is the indication for PDN which is acknowledged in the S-1. By far the biggest opportunity in a therapeutic for neuropathic pain exists for this disorder. Apparently Neurogesx plans to file the broad label authorization for NGX-4010 MAA in
Next time I’ll wrap up with the Neurogesx financial situation and put it all together for a final verdict.
Disclosure: I have no position in NGSX