FDA May Delay Approval of New Opioid Drugs

FDA May Delay Approval of New Opioid Drugs

The Food and Drug Administration is asking for additional studies on the safety of a powerful new opioid medicine designed to treat constipation. The FDA’s concerns about possible cardiovascular risks raised uncertainty among investors and caused one analyst to downgrade the stock of a drug maker, citing regulatory concerns.

Jefferies & Company downgraded its rating on Nektar Therapeutics  (NASDAQ: NKTR) from a buy to a hold, and lowered its price target from $10 to $8. Nektar recently completed Phase III studies on naloxegol, its constipation pain medicine. Constipation is a common side effect of prescription opioids.

“Recent FDA scrutiny on CV (cardiovascular risks) with chronic opioid antagonist use translates to higher approval hurdles potentially involving additional large CV outcome studies and potentially delaying naloxegol’s approval/launch,” Jeffries said in a research note to clients.

Last week Salix Pharmaceuticals (NASDAQ:SLXP) and Progenics (NASDAQ:PGNX) disclosed that the FDA wants a large, long-term safety study conducted before their constipation drug Relistor will be approved. The chief concern is whether opioid withdrawal symptoms from Relistor may trigger a cardiovascular event or heart attack in patients.

The FDA’s concerns about Relistor prompted Nektar to warn investors that a similar study may be required for naloxegol, also known as NKTR-118.

“The health authorities retain significant discretion over regulatory requirements which remain very uncertain and difficult to predict prior to obtaining approval,” Nektar said in an SEC filing.

Hoping to put a positive spin on the drug’s progress, Nektar partner AstraZeneca (NYSE: AZN) reported positive results from two Phase III studies, and said there were no “clinically relevant imbalances” in cardiovascular events between patients treated with naloxegol and a placebo.

The most common adverse side effects reported in both trials were abdominal pain, diarrhea and nausea. However, those studies were brief, lasting 12 and 24 weeks. The results of a one year study of naloxegol currently underway won’t be released until early next year.

It’s not clear if the FDA will require Nektar and AstraZeneca to conduct further safety studies. But any delays in development will be costly to Nektar. The drug maker will receive $95 million from AstraZeneca when naloxegol is submitted to the FDA for approval. AstraZeneca will pay Nektar another $140 million if naloxegol is approved and launched commercially in the U.S. and Europe.

“I can’t comment on confidential discussions with FDA and I can’t speculate on what the FDA might do or might not do. We’re aware that the FDA is exploring whether there’s evidence of a cardiovascular risk,” said Howard Robin, Nektar’s President and CEO, in a conference call Monday with analysts. “Anything that we might have seen has been very mild. We don’t see any cardiovascular risk signal in these studies.”

“I think, at this point we’re very, very happy with the safety profile of naloxegol,” Robin said in a transcript of the call on Seeking Alpha.

Opioids work by attaching to specific proteins called opioid receptors. When receptors located in the brain or central nervous systems are blocked, pain is reduced. But when the opioids attach to receptors in the gastrointestinal tract, there’s a decrease in fluid absorption and constipation may occur.

Naloxegol is one of several drugs being developed to address the stubborn constipation that affects about half the 35 million patients worldwide who take opioids for chronic, long term, non-cancer pain relief.

Although the FDA has not explained why it’s now concerned about the safety of the drugs, there is speculation that is was prompted by heart attacks associated with Entereg, a drug sold by Cubist Pharmaceuticals (NASDAQ: CBST), and approved to speed the recovery of bowel function in patients following abdominal surgery.

Authored by: Richard Lenti