Sanofi and Regeneron itching to move dupilumab into phase III

Sanofi’s long-term collaboration with Regeneron Pharmaceuticals is looking tantalisingly close to paying even bigger dividends for the US big biotech. The latest development is a successful phase IIb readout for eczema injection dupilumab.

The partners announced that the antibody significantly reduced the size and severity of lesions in patients with moderate to severe disease at all five of the dose levels tested. If these promising signs are confirmed in pivotal trials, it could be the first interleukin modulator proven to treat atopic dermatitis.

Spoilt for choice

Interleukin modulators have already shown that they can effectively treat inflammatory disease – Johnson & Johnson’s IL-12 and 23 antibody Stelara is a blockbuster in plaque psoriasis and psoriatic arthritis. The closely related cytokines IL-4 and 13, which dupilumab blocks, are associated with allergic and airway response.

Sanofi and Regeneron announced that the trial in 380 patients showed that all doses of dupilumab, a monoclonal antibody injected subcutaneously, met the primary endpoint of a statistically greater improvement in the eczema area and severity index (EASI) from baseline over 16 weeks than placebo.

The doses ranged from 300mg weekly to 100mg monthly. Patients taking the former dose saw a 74% reduction in EASI and the latter 45%, compared with 18% for patients in the placebo arm. Nasopharyngitis adverse events were roughly equal in the active and control arms, although a greater number of patients taking dupilumab experienced injection site reactions and headache.

The other dosage groups included 300mg every other week, 300mg monthly and 200mg every other week; the partners did not disclose efficacy data on the other dose groups. However, the statistically significant benefit seen in all the dosage groups should give the partners many choices when designing the pivotal programme, which is expected to begin later this year.

EvaluatePharma’s consensus forecasts $467m in sales by 2020, a number that could rise as analysts become more comfortable with dupilumab’s promise. Likewise, Regeneron analysts have not forecast any royalties, so those estimates could change.

Win-win yet?

The collaboration between the two groups dates back more than a decade, when Regeneron and Sanofi's predecessor company Aventis signed a deal to develop VEGF-Trap, the colorectal cancer drug now known as Zaltrap. That drug is reckoned to be on track to sell more than half a billion dollars by 2020, but because of the terms of that deal, Regeneron is still paying back collaboration costs to Sanofi – $30.8m in 2013, according to the Regeneron’s annual report.

Thus the company and its investors probably want to see a bigger payoff from the relationship. The two expanded the partnership in 2007 to include products from its monoclonal antibody technology VelocImmune, an agreement that also saw the French group take a one-fifth stake in Regeneron.

The leading candidate from the collaboration is the rheumatoid arthritis injection sarilumab, which has reported positive phase III data. No word on regulatory filings has come, but some analysts are forecasting a 2015 launch. The anti-PCSK9 MAb alirocumab is another late-stage product from the collaboration.

What Regeneron needs is for these projects to begin generating sustainable revenue. Zaltrap has yet to produce a penny in royalty income, so investors would surely like to see signs that the Sanofi collaboration will have more benefits for both sides.

To contact the writer of this story email Jonathan Gardner in London at jonathang@epvantage.com or follow @JonEPVantage on Twitter

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