Another day, another drug on hold. Two in fact.

On Monday, Regeneron Pharmaceuticals (Nasdaq: REGN) said the anti-nerve growth factor (NGF) drug it's developing with sanofi-aventis (NYSE: SNY) was put on clinical hold.

Yesterday, it was both AstraZeneca (NYSE: AZN) and Johnson & Johnson (NYSE: JNJ) disclosing that they were pausing development of their anti-NGF drugs. Apparently AstraZeneca's medi-578 has been on a voluntary hold since July, but since the company is so large, it wasn't necessary to disclose it (or we all just missed it). Johnson & Johnson, like Regeneron, found out from the FDA last week that its drug, fulranumab, was being put on hold.

Nerve growth factor, as you might guess, stimulates the growth of nerve cells, but it also sensitizes and/or activates the pain response. NGF is increased in many types of chronic pain, so sequestering NGF seemed like a good way to reduce the pain. And it apparently was.

In a phase 3 trial, Pfizer's (NYSE: PFE) anti-NGF antibody, tanezumab, produced a statistically significant reduction in pain compared to placebo in patients with osteoarthritis in their knee.

But as the phase 3 program progressed, Pfizer noted that a "small number" of patients' osteoarthritis got worse, and the FDA put the program on a clinical hold.

Given the additional clinical holds, the FDA is apparently worried that the shared mechanism of action for all the anti-NGF molecules is the reason for worsening of osteoarthritis. The only anti-NGF drug still standing at this point seems to be Abbott Labs' (NYSE: ABT) ABT-110, but you have to figure Abbott could easily be getting a similar call from the FDA shortly.

Theoretically, the companies could get over this issue. Maybe by proving that it's specific to osteoarthritis, they might be able to get the drugs approved in other chronic pain indications like lower back pain or nerve pain that's associated with diabetes. But the potential side effect is always going to be hanging over anti-NGF drugs. Even if the FDA signs off on the drugs, it's unlikely the anti-NGF drugs will live up to their potential.

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