* FDA asks for more data on Probuphine
* Titan shares fall 72 percent in early trading
* Titan says extremely surprised and disappointed by ruling
By Toni Clarke
May 1 U.S. health regulators rejected an
experimental drug to treat opioid addiction made by Titan
Pharmaceuticals Inc and asked for additional data
showing it works, the company said.
The drug, Probuphine, is a long-acting version of
buprenorphine, a drug sold by British rival Reckitt-Benckiser
Group Plc under the brand names Subutex and Suboxone.
Unlike Subutex and Suboxone, which are taken daily and
dissolved under the tongue, Titan's drug is implanted under the
skin of the upper arm during a 10- to 15-minute office procedure
and delivers a continuous supply of buprenorphine for six
Clinical data showed Probuphine to be more effective than
placebo in curbing addiction, but an outside panel of experts to
the FDA said in March that the data were not particularly robust
and suggested the proposed Probuphine dose could be too low.
Even so, the panel voted 10-4 with one abstention that the
drug be approved, with the proviso that Titan clarify the most
effective dose and establish a strong plan to mitigate any risk
of abuse. In its rejection letter, the FDA asked, among other
things, for data showing the effect of higher doses of the drug.
"I'm surprised (at the FDA rejection), given the positive
advisory committee vote," said Jason Napodano, an analyst at
Zacks Investment Research. "I thought given the outcome of the
panel, the FDA was going to approve the device."
Napodano said it was unclear whether Titan already has the
data or will need to generate it through new clinical studies.
Titan's stock fell 41 percent after the expert panel's
comments on March 19. The stock plunged 72 percent to $0.45 a
share in early trading on Wednesday.
Titan, which announced the FDA decision shortly before
midnight on Tuesday, said it was "extremely surprised and
disappointed" with the agency's response. The formulation of
Probuphine is consistent with recently issued FDA guidance
supporting diversion and abuse-resistant drugs, the company
In December, Titan licensed the U.S. and Canadian rights to
Probuphine to Braeburn Pharmaceuticals, a company owned by the
venture capital firm Apple Tree Partners. Titan received an
up-front payment of $15.75 million and would have received an
upfront payment of $50 million if Probuphine had been approved.
To date, the market for buprenorphine has been dominated by
Reckitt, a consumer goods company whose products range from
cleaning supplies to condoms. Subutex and Suboxone generated
sales of roughly $1.3 billion in 2012.
Suboxone and Subutex lost market exclusivity in 2009, and
while generic competitors promptly introduced cheap copies of
Subutex, they were slow to develop alternatives to Suboxone. In
the meantime, Reckitt persuaded many physicians to switch from
Suboxone tablets to Suboxone Film, its newer, patent-protected
wafer-like strip that patients dissolve under the tongue. At the
end of 2012, according to Reckitt, Suboxone Film had captured 64
percent of the market.
Earlier this year, the FDA approved generic versions of
Suboxone tablets from Amneal Pharmaceuticals LLC and Actavis Inc