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.”

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Fangliang Zhang, AP Images

UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 83,200+ biopharma pros reading Endpoints daily — and it's free.

As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 83,200+ biopharma pros reading Endpoints daily — and it's free.

Bris­tol My­ers is clean­ing up the post-Cel­gene merg­er pipeline, and they’re sweep­ing out an ex­per­i­men­tal check­point in the process

Back during the lead up to the $74 billion buyout of Celgene, the big biotech’s leadership did a little housecleaning with a major pact it had forged with Jounce. Out went the $2.6 billion deal and a collaboration on ICOS and PD-1.

Celgene, though, also added a $530 million deal — $50 million up front — to get the worldwide rights to JTX-8064, a drug that targets the LILRB2 receptor on macrophages.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 83,200+ biopharma pros reading Endpoints daily — and it's free.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.

UP­DAT­ED: Es­ti­mat­ing a US price tag of $5K per course, remde­sivir is set to make bil­lions for Gilead, says key an­a­lyst

Data on remdesivir — the first drug shown to benefit Covid-19 patients in a randomized, controlled trial setting — may be murky, but its maker Gilead could reap billions from the sales of the failed Ebola therapy, according to an estimate by a prominent Wall Street analyst. However, the forecast, which is based on a $5,000-per-course US price tag, triggered the ire of one top drug price expert.