Archive for June, 2010

Neurocrine and Abbott’s elagolix – have they found the right parameters to measure endometriosis pain?

Posted by lifetech on June 29th, 2010

Neurocrine Biosciences has just completed phase II trials of elagolix (an oral GnRH antagonist) for endometriosis. It also recently announced a partnership with Abbott. The path through phase II was difficult, as Neurocrine struggled to find the appropriate endpoints with which to measure the effect of treatment on disease-associated pain. The drug is clearly active: it suppresses estradiol and interrupts the menstrual cycle — the intended pharmacological effects suggested by its mechanism of action. However, the goal of showing that therapy consistently relieves pain was more elusive and early trials showed mixed results. Encouragingly, the last trial in the series, Daisy PETAL, demonstrated robustly positive efficacy. But the pending question is whether Neurocrine has finally identified a winning set of parameters for designing phase III trials, or whether the difficulties seen throughout the earlier trials will continue to haunt further studies. If it succeeds in pivotal trials, elagolix will enter a competitive market with various agents used on and off label for endometriosis. But Neurocrine and Abbott are betting that elagolix’s differentiated safety profile will provide the market edge it needs to capture greater market share. We refer you to LifeTech’s report for our take on elagolix and its prospects.

Pfizer hits Tanezumab’s safety iceberg

Posted by lifetech on June 25th, 2010

On June 23rd, Pfizer announced that FDA put its Tanezumab osteoarthritis phase III program on hold, following reports of worsening disease among patients receiving the antibody, which targets NGF (nerve growth factor). This came as no surprise to us. As we wrote back in November, “Tanezumab has titanic potential, but there are looming safety icebergs”.

NGF is involved in many vital physiological pathways, not just in the nervous system but also in the immune and neuroendocrine systems. Thus it is likely that other toxicities should emerge once the molecule’s action is blocked. As we discuss in our report, based on NGF’s role, possible consequences of its inhibition include peripheral neuropathy, dementia or other central nervous system dysfunction, increased rate of infection, slow wound healing or metabolic dysfunction. In fact, some evidence of these adverse effects has already been observed in phase II. In addition, it is certainly disturbing that there is sufficient rationale to test recombinant NGF itself (ie, the opposite pharmacologic effect of Tanezumab) as a treatment for Alzheimer’s disease – and such trials are underway by other companies. If that strategy is effective, doesn’t it suggest that anti-NGF therapies such as Tanezumab may accelerate or predispose patients to Alzheimer’s disease?

Our report provides an in-depth discussion of the observed and theoretical safety concerns of Tanezumab based on the known role of NGF. The chronic pain market potential is enormous. Pfizer is pursuing seven clinical indications, with a combined market potential of up to $6BN in the US alone. Osteoarthritis, the most advanced clinical indication, represents about a third of that opportunity. Even if osteoarthritis is out of the picture, the opportunity for Tanezumab is still huge – should it safety profile permit…

JAZZ PHARMACEUTICALS’ XYREM – Can this notorious drug find redemption in fibromyalgia?

Posted by lifetech on June 12th, 2010

We just published a report on sodium oxybate – better known as GHB, a powerful nervous system depressant that gained notoriety in the 1990s as a  “date rape” drug. Despite its reputation and schedule I restriction, FDA approved a branded GHB formulation, Xyrem, for treating narcolepsy. In 2009, Xyrem sales accounted for about $97 million in revenue for Jazz Pharmaceuticals, which is now seeking to expand the market opportunity for Xyrem into fibromyalgia, a much more prevalent condition.

Jazz reported positive phase III studies last year and submitted its marketing application to FDA, putting it on track for a regulatory decision in mid-October. An approval would be a boon to Jazz. But will FDA view significant efficacy as sufficient to justify approval in a much broader population with a non-life-threatening condition, given the complex history and track record of GHB in other settings? In this report we weigh these and other issues as we attempt to gauge the likelihood of regulatory success for Xyrem this Fall in fibromyalgia