NICE backs decades-old bladder pain drug Elmiron despite 'uncertainty' over clinical evidence

Can a decades-old drug with “substantial uncertainty” over its clinical evidence still win public health coverage in England? In bladder pain drug Elmiron’s case, the answer is “yes”—but not without a price discount and some use restrictions.

England’s National Institute for Health and Care Excellence (NICE) has decided to recommend (PDF) Elmiron for NHS coverage as a treatment for treating bladder pain syndrome. The drug, sold by Johnson & Johnson’s Janssen since the late 1990s in the U.S., only won official EU approval mid-2017 by bene-Arzneimittel and is distributed in the U.K. by Consilient Health.

The recommendation marks a change of mind at the drug cost watchdog, which in July shot Elmiron down over cost-effectiveness concerns. But this time, NICE is allowing the drug “for a defined population” after Consilient Health offered a confidential discount to the NHS. Before the cut, a pack of 90 capsules cost £450 ($553).

Within Elmiron’s EMA-approved indication—bladder pain syndrome with either glomerulations or Hunner’s lesions—NICE will further limit Elmiron’s use to patients who do not respond to other oral treatments and exclude patients who already respond to such drugs as Uracyst, which is a fluid that’s instilled into the bladder. Elmiron is the only oral drug that’s specifically approved to treat bladder pain syndrome, also known as interstitial cystitis, in the EU.

In its evaluation, the review committee found Elmiron “not cost-effective compared with best supportive care.” However, it also said the most plausible estimates for Elmiron compared with bladder instillations are “likely to be a cost-effective use of NHS resources.”

The clinical data around Elmiron by itself was clearly not enough to win over NICE. In a meta-analysis of four older clinical trials—involving 454 patients altogether—that helped Elmiron win EU approval in June 2017, the drug topped placebo at improving pain, urinary urgency and urinary frequency. However, NICE experts found the trials used inconsistent and non-validated methods for assessing symptoms and identified “substantial uncertainty” in the clinical evidence.

In Consilient’s second try, the company pitted Elmiron as an alternative to invasive bladder instillations. In a cross-trial analysis, Elmiron elicited a response in 33% of patients, while bladder instillations achieved a 22% response rate, even though both the company and the committee acknowledged such an indirect comparison can be problematic.

About 400,000 people in the U.K. have bladder pain syndrome but only about 10% will seek treatment, clinical experts told NICE. According to a November 2017 presentation by Navamedic, which holds Nordic commercial rights to Elmiron, the drug returned over $250 million in U.S. sales to J&J in 2016.