InterMune rides high on pirfenidone wave

InterMune appears to be succeeding where others have failed with pirfenidone, its treatment for idiopathic pulmonary function (IPF). With the proposed new brand name Esbriet, the tumour necrosis factor-alpha inhibitor was forwarded to the FDA with a favourable advisory committee vote Tuesday, making it potentially the first disease-modifying drug for a degenerative disease that affects 100,000 in the US.

Shares in the California firm rocketed 66% to $38.68, an eight-year high, in early trading in the wake of the 9-3 vote in favour of pirfenidone’s approval from the FDA’s Pulmonary-Allergy Drugs Advisory Committee; an unsurprising performance considering the drug could be worth $1.29bn to InterMune, according to EvaluatePharma's NPV Analyzer (Event - InterMune races for open field with Tracleer failure, March 2, 2010).

Mixed trial results

What may be a little more surprising is the vote supporting the drug. InterMune prevailed despite the failure of one of pirfenidone’s two phase III trials to show a statistically significantly slowing of the decline in lung function, the primary endpoint (Mixed pirfenidone data improves InterMune's capacity, February 3, 2009). In its analysis of Intermune’s submission, FDA staff noted that the agency usually requires more than one trial to demonstrate efficacy, even for orphan drugs, as pirfenidone is.

Moreover, the FDA staff cautioned that in trials there were more patients in the pirfenidone arms than in the placebo arms who reported adverse events and more discontinued treatment. Widespread use of the drug is likely to create safety concerns for the FDA as it approaches its PDUFA date of May 4.

However, in a conference call following the adcom vote, Daniel Welch, InterMune’s president, said the company had proposed a risk evaluation and mitigation strategy (REMS) and will be in discussions with FDA staff about its proposal in advance of the PDUFA date.

Market dominance

IPF is an always fatal condition with a median survival time of two to five years. With no disease-modifying drugs on the market, it is usually managed with corticosteroids (Therapeutic focus - Behind Tracleer pulmonary fibrosis pipeline is a trickle, January 18, 2010). As a first-to-market drug, pirfenidone is likely to dominate, depending on how quickly InterMune can commercialise should the FDA approve it, and may be able to charge as much as $40,000 a year. Mr Welch would not discuss the company’s commercial plans nor its pricing in the conference call, however.

With the recent failure of Actelion’s Tracleer in phase III trials for IPF (Actelion stopped in tracks with negative Tracleer data, March 1, 2010), the promise of market dominance looms even larger. Letairis, the Gilead Sciences' pulmonary hypertension drug, also known as GlaxoSmithKline’s Volibris outside the US, is in phase III trials, but it is also an endothelin A receptor antagonist like Tracleer and may have similar difficulties. Phase III data for that drug is not expected until late 2012 or early 2013.

As a sign of pirfenidone’s likely market dominance, EvaluatePharma’s February consensus forecast estimates 2014 sales at $482m. However, that estimate is down markedly from as much as $917m in December 2008 and $768m in January 2010, largely reflecting a broader consensus view of the drug as gradually more analysts cover the company .

In Japan, where it is already approved and sold by partner Shionogi under the name Pirespra, it is forecast to have $28m in sales this year, rising to $65m by 2014. Mr Welch noted, however, that Japanese sales were restricted under a strict safety surveillance scheme.

Forecasts are of course dependent on FDA approval, and it is always important to note that adcom blessings are no guarantee of that. Although it is undoubtedly helpful to have adcom support, there must be more than a little bit of concern about the failure of one of the phase III trials to show efficacy. With that chink in InterMune’s armour, it may be that no amount of unmet clinical need will appease the FDA if it wants absolute certainty about pirfenidone’s efficacy and safety.

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