Pfiz­er, Mer­ck KGaA score a land­mark FDA OK for check­point con­tender avelum­ab

Lu­ciano Ros­set­ti, Mer­ck Serono

Mer­ck KGaA and Pfiz­er have done it.

The bio­phar­ma part­ners came away with their first FDA ap­proval of the check­point in­hibitor avelum­ab, mak­ing it the fourth drug in this cat­e­go­ry to make it to the mar­ket. They beat As­traZeneca, which will now an­gle for its first ap­proval of dur­val­um­ab as the 5th check­point.

The FDA gave out its ap­proval for Merkel cell car­ci­no­ma un­der an ac­cel­er­at­ed ap­proval process. The ther­a­py, the first for a rare form of skin can­cer, has al­so been giv­en break­through drug sta­tus. The drug is cur­rent­ly in 30 clin­i­cal pro­grams as the two play­ers look to wedge their way in­to a multi­bil­lion-dol­lar mar­ket for drugs that are gain­ing wide use in treat­ing can­cer.

The ap­proval marks an­oth­er big ad­vance for Pfiz­er, which paid $850 mil­lion up­front to part­ner with Ger­many’s Mer­ck — a record sum. The ap­proval of this an­ti-PD-L1 IgG1 mon­o­clon­al an­ti­body al­so marks a ma­jor win for Mer­ck KGaA, which has suf­fered through more than a decade with­out a block­buster OK. Mer­ck KGaA al­so came away with a pack­age of reg­u­la­to­ry and com­mer­cial mile­stones on avelum­ab worth up to $2 bil­lion when it tied up with Pfiz­er in 2014.

The ther­a­py will be sold as Baven­cio. A spokesper­son for Pfiz­er said the drug will cost $13,000 a month whole­sale — ahead of pay­er dis­counts.

The new ap­proval marks just how quick­ly the FDA can move when it wants to. The OK is based on a sin­gle arm study in­clud­ing 88 pa­tients. Of the 88 pa­tients who re­ceived Baven­cio in the tri­al, says the FDA, 33% ex­pe­ri­enced com­plete or par­tial shrink­age of their tu­mors. The re­sponse last­ed for more than six months in 86% of re­spond­ing pa­tients and more than 12 months in 45% of re­spond­ing pa­tients.

Not on­ly was avelum­ab a big suc­cess as a check­point, the de­vel­op­ment pro­gram from start to first ap­proval was ex­e­cut­ed swift­ly.

“Three-and-a-half years af­ter the first-in-hu­man dose es­ca­la­tion stud­ies, we are get­ting our first ap­proval,” says Lu­ciano Ros­set­ti, the head of R&D at Mer­ck Serono. And don’t ex­pect any­one to start sit­ting on lau­rels. Check­point in­hi­bi­tion is a big field, and the Pfiz­er/Mer­ck KGaA team plan to make their mark as the pi­o­neers divvy up lead­er­ship roles in a wide ar­ray of can­cers.

As­traZeneca re­jigged its de­vel­op­ment cam­paign for the next check­point in the pipeline, re­ly­ing heav­i­ly on its work in com­bin­ing it with the CT­LA-4 check­point treme­li­mum­ab to try and leapfrog the fast mov­ing trio in the lead: Mer­ck, Bris­tol-My­ers Squibb and Roche/Genen­tech. They’ll be star­ing down some of the biggest ri­vals in the in­dus­try in a make-or-beak ef­fort to dis­tin­guish its R&D op­er­a­tions, which has had sev­er­al suc­cess­es in can­cer but con­tin­ues to be plagued by set­backs in the clin­ic and at the FDA.

You can add Mer­ck KGaA to the list now.

“You need to have a strong PD1/ PD-L1 to an­chor com­bi­na­tions for oth­er as­sets,” Ros­set­ti tells me. And now they have one ap­proved and en­ter­ing the mar­ket.

The FDA ac­cept­ed their ap­pli­ca­tion for urothe­lial car­ci­no­ma just a few weeks ago, and Ros­set­ti says they’re push­ing hard on ovar­i­an, gas­tric and lung can­cer work that could pave the way for near-term ap­provals.

“To be prac­ti­cal,” he adds, “the biggest op­por­tu­ni­ty is in non-small cell lung can­cer.” One of those big op­por­tu­ni­ties is demon­strat­ing an ef­fect in low PD-L1 ex­pressers with re­searchers al­so ex­plor­ing high in­ten­si­ty ther­a­py for high ex­pressers.

Ros­set­ti, though, is care­ful to of­fer no big promis­es on what the da­ta will show. He’s acute­ly aware that when they mod­i­fied the lung can­cer study, the com­pa­ny was gam­bling on a dis­ease that proved a dis­as­ter for Bris­tol-My­ers Squibb and a chance for Mer­ck to leap ahead of the pack.

The first thing that Ros­set­ti did when he was named R&D chief in 2014 was to fo­cus the pipeline, get­ting rid of 13 pro­grams so they could con­cen­trate on a few se­lect ef­forts like avelum­ab. Now he says the com­pa­ny is in­ter­est­ed in do­ing a few deals to help beef up its fo­cus on com­bi­na­tions and more. But they’ll be very strate­gic about launch­ing new tri­als.

“While skin can­cer is one of the most com­mon can­cers, pa­tients with a rare form called Merkel cell can­cer have not had an ap­proved treat­ment op­tion un­til now,” said Richard Paz­dur, MD, act­ing di­rec­tor of the Of­fice of Hema­tol­ogy and On­col­o­gy Prod­ucts in the FDA’s Cen­ter for Drug Eval­u­a­tion and Re­search and di­rec­tor of the FDA’s On­col­o­gy Cen­ter of Ex­cel­lence. “The sci­en­tif­ic com­mu­ni­ty con­tin­ues to make ad­vances tar­get­ing the body’s im­mune sys­tem mech­a­nisms for the treat­ment of var­i­ous types of can­cer. These ad­vance­ments are lead­ing to new ther­a­pies—even in rare forms of can­cer where treat­ment op­tions are lim­it­ed or non-ex­is­tent.”

5AM Ven­tures: Fu­el­ing the Next Gen­er­a­tion of In­no­va­tors

By RBC Capital Markets
With Andy Schwab, Co-Founder and Managing Partner at 5AM Ventures

Key Points

Prescription Digital Therapeutics, cell therapy technologies, and in silico medicines will be a vital part of future treatment modalities.
Unlocking the potential of the microbiome could be the missing link to better disease diagnosis.
Growing links between academia, industry, and venture capital are spinning out more innovative biotech companies.
Biotech is now seen by investors as a growth space as well as a safe haven, fuelling the recent IPO boom.

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