As­traZeneca, Mer­ck­'s star PARP in­hibitor Lyn­parza ex­pands reach in ovar­i­an can­cer with new US ap­proval

Weeks af­ter GSK widened the mar­ket for PARP in­hibitor Ze­ju­la in pa­tients with ovar­i­an can­cer, ri­val As­traZeneca’s mar­ket-lead­ing Lyn­parza has al­so se­cured ex­pand­ed use in women with the dis­ease.

Lyn­parza, in com­bi­na­tion with Roche’s Avastin, has been ap­proved by the FDA for the main­te­nance treat­ment of adult pa­tients with ad­vanced ep­ithe­lial ovar­i­an, fal­lop­i­an tube or pri­ma­ry peri­toneal can­cer who have ex­pe­ri­enced a com­plete or par­tial re­sponse to first-line plat­inum-based chemother­a­py and whose dis­ease is as­so­ci­at­ed with ho­mol­o­gous re­com­bi­na­tion de­fi­cien­cy (HRD) pos­i­tive sta­tus, de­fined by ei­ther a BR­CA mu­ta­tion and/or ge­nom­ic in­sta­bil­i­ty. Rough­ly one in two women with ad­vanced ovar­i­an can­cer has an HRD+ tu­mor.

Al­though drug de­vel­op­ers have large­ly leaned on BR­CA mu­ta­tions to iden­ti­fy pa­tients who can ben­e­fit from PARP in­hibitors, sci­en­tists have sug­gest­ed that de­fects in oth­er genes in­volved in DNA re­pair — which ren­der cells can­cer­ous — could be prime tar­gets too.

The new Lyn­parza ap­proval is based on the late-stage PAO­LA-1 tri­al, which showed the ad­di­tion of the PARP in­hibitor to Avastin ther­a­py re­duced the risk of dis­ease pro­gres­sion or death by 67%, and that the com­bi­na­tion im­proved pro­gres­sion-free sur­vival (PFS) to a me­di­an of 37.2 months ver­sus 17.7 months in pa­tients with HRD pos­i­tive ad­vanced ovar­i­an can­cer who were on­ly giv­en Avastin.

“We ex­pect grad­ual up­take in the HRD+ set­ting, as ge­net­ic se­quenc­ing be­comes more in­te­grat­ed in­to treat­ment par­a­digms. Be­yond the HRD+ in­di­ca­tion, the PARP class may be more chal­lenged giv­en the su­pe­ri­or ef­fi­ca­cy of Avastin in these pa­tients. How­ev­er, Avastin us­age re­quires in­tra­venous ad­min­is­tra­tion and is as­so­ci­at­ed with a num­ber of side ef­fects that may make oral PARP us­age more de­sir­able, es­pe­cial­ly in the COVID en­vi­ron­ment,” SVB Leerink an­a­lysts said.

The ap­proval will al­so se­cure for As­traZeneca $100 mil­lion in col­lab­o­ra­tion rev­enue from part­ner Mer­ck.

Akin to Lyn­parza, GSK’s Ze­ju­la and Clo­vis’ Rubra­ca are poly ADP-ri­bose poly­merase (PARP) in­hibitors. PARP is a pro­tein used by dam­aged cells to ini­ti­ate re­pair, and by thwart­ing it, the class of drugs is en­gi­neered to pre­vent can­cer cells from re­pair­ing them­selves, there­by cat­alyz­ing their de­struc­tion.

Last Oc­to­ber, Ze­ju­la was ap­proved for use in ovar­i­an can­cer pa­tients with HRD+ tu­mors who have been through (and were sen­si­tive to) at least three rounds of chemother­a­py. But in late April, Ze­ju­la’s use was ex­pand­ed — on the ba­sis of the PRI­MA tri­al — to women with ovar­i­an can­cer who ex­pe­ri­enced a com­plete or par­tial re­sponse to first-line plat­inum-based chemother­a­py — ac­count­ing for ap­prox­i­mate­ly 80% of all ovar­i­an can­cer pa­tients — this ap­proval in­clud­ed in­clud­ing HRD neg­a­tive pa­tients.

“While this does open the door for Ze­ju­la to be the on­ly PARP that has for­mal ap­proval for use in 1L ovar­i­an can­cer pa­tients with­out a mark­er of re­pair de­fi­cien­cy (HRD-), the drug may face com­mer­cial chal­lenges in this HRD- group, giv­en Avastin monother­a­py main­te­nance demon­strat­ed ~2x the ef­fi­ca­cy of PARP monother­a­py main­te­nance based on a com­par­i­son be­tween PAO­LA-1 and PRI­MA tri­al re­sults,” SVB Leerink an­a­lysts wrote in a note.

“We think some clin­i­cians may be re­luc­tant to ad­min­is­ter a PARP with­out de­ter­min­ing HRD sta­tus giv­en that about 2/3 of non-BR­CA+ pa­tients, the HRD- co­hort, may get less ef­fi­ca­cy with a PARP than with Avastin.”

As the sec­ond-to-mar­ket drug in the class, Ze­ju­la gen­er­at­ed ~25% of the rev­enue Lyn­parza did last year — £229 mil­lion ver­sus £921 mil­lion.

Next up on the dock­et for As­traZeneca and Mer­ck’s Lyn­parza is an ap­proval for a sub­set of pa­tients with metasta­t­ic cas­tra­tion-re­sis­tant prostate can­cer, af­ter the com­pa­nies re­port­ed a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in over­all sur­vival.

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.

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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.

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.

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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.

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.

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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.

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Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.