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.

Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

A lab technician works during research on coronavirus at Johnson & Johnson subsidiary Janssen Pharmaceutical in Beerse, Belgium, Wednesday, June 17, 2020. (Virginia Mayo/AP Images)

End­points News ranks all 28 play­ers in the Covid-19 vac­cine race. Here's how it stacks up to­day

The 28 players now in or close to the clinical race to get a Covid-19 vaccine over the finish line are angling for a piece of a multibillion-dollar market. And being first — or among the leaders — will play a big role in determining just how big a piece.

Endpoints News writer Nicole DeFeudis has posted a snapshot of all the companies, universities and hospital-based groups now racing through the clinic, ranking them according to their place in the pipeline as well as the latest remarks available on timelines. And we’ll keep this lineup updated right through the end of the year, as the checkered flags start to fall, possibly as early as October.

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Bayer's Marianne De Backer with Endpoints founder John Carroll, Endpoints@JPM20 (Jeff Rumans for Endpoints News)

UP­DAT­ED: Hunt­ing a block­buster, Bay­er forges an $875M-plus M&A deal to ac­quire women’s health biotech

Bayer has dropped $425 million in cash on its latest women’s health bet, bringing a UK biotech and its non-hormonal menopause treatment into the fold.

KaNDy Therapeutics had its roots in GlaxoSmithKline, which spun out several neuroscience drugs into NeRRe Therapeutics back in 2012. Five years later the team created a new biotech to focus solely on NT-814 — which they considered “one of the few true innovations in women’s health in more than two decades.”

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Phase III read­outs spell dis­as­ter for Genen­tech’s lead IBD drug

Roche had big plans for etrolizumab. Eyeing a hyper-competitive IBD and Crohn’s market where they have not historically been a player, the company rolled out 8 different Phase III trials, testing the antibody for two different uses across a range of different patient groups.

On Monday, Roche released results for 4 of those studies, and they mark a decided setback for both the Swiss pharma and their biotech sub Genentech, potentially spelling an end to a drug they put over half-a-decade and millions of dollars behind.

Eisai moves to 200 Metro Blvd. by late 2021 (ON3)

Ei­sai is cre­at­ing a new US cor­po­rate, R&D HQ in Roche’s old Nut­ley, NJ cam­pus

Eight years after Roche pulled up stakes from Nutley, NJ in a major R&D reorganization, Japan’s Eisai is moving its US corporate and research hub into their old campus.

Now the ON3 property, Eisai — a longtime Biogen partner focused on neurodegenerative disorders like Alzheimer’s — will bring together a staff of up to 1,200 employees. And execs are pitching the move to the New Jersey campus as a cultural game-changer.

DFC CEO Adam Boehler and Kodak CEO Jim Continenza (Kodak)

Covid-19 roundup: Cure­Vac beefs up its uni­corn IPO dreams as bil­lion­aire own­er takes this Covid-19 mR­NA play­er on a forced march to Nas­daq; Ko­dak's $765M deal is put on hold

When CureVac initially jotted down $100 million for its IPO raise a couple of weeks ago, it seemed small. The German mRNA player, after all, had jumped into a Covid-19 race that swelled the sails of Moderna and BioNTech by tens of billions. And after raising $640 million in a slate of deals, $100 million in a hot market like this seemed like a pittance in the bigger scheme of things.

Today, we got a look at a figure that probably comes closer to the game-changing number the top execs probably have in mind. Selling 15.3 million shares at the high end of their $14 to $16 range would net a $243 million bounty. Majority owner Dietmar Hopp is putting in another €100 million, bringing the total to around $350 million. And what are the chances they want to do even better than that?

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FDA gives thumbs-down on hear­ing loss drug, cit­ing man­u­fac­tur­ing is­sues, and sends Fen­nec stock reel­ing

A small, North Carolina-based biotech has run into some headwinds in its efforts to develop a compound that prevents hearing loss associated with cisplatin chemotherapy treatments.

The FDA handed down a complete response letter to Fennec Pharmaceuticals $FENC for its Pedmark drug late Monday night, citing manufacturing issues with the company’s supplier. Fennec hopes to meet with regulators sometime within the next month or two, CEO Rosty Raykov said in a call with investors Tuesday morning, in order to resolve the issue.

Ugur Sahin, BioNTech CEO

Covid-19 roundup: Pfiz­er-backed BioN­Tech plans to seek FDA OK for a new vac­cine 'as ear­ly as' Oc­to­ber — ahead of the elec­tion

BioNTech execs say they’re on track to get their late-stage data on a Covid-19 vaccine — partnered with Pfizer — into the hands of regulators as early as October.

In their Q2 release Tuesday morning, the biotech reported that investigators could have late-stage data as early as October, and they won’t be wasting any time in hustling that over to the FDA.

“I am incredibly proud of our team, who has worked tirelessly to initiate our BNT162 Phase 2b/3 trial in record time and put us in a position to seek regulatory review as early as October of this year, if our trials are successful,” said Ugur Sahin, BioNTech’s CEO and co-founder.

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Warren Huff, Reata CEO

UP­DAT­ED: Rea­ta sug­gests Friedre­ich's atax­ia pro­gram could be de­layed, send­ing stock plung­ing

Reata Pharmaceuticals $RETA made waves last October when its drug omaveloxolone produced positive trial results in treating a rare neurological disorder, but the candidate’s path forward became much murkier Monday.

In a report of quarterly earnings, the biotech divulged that the FDA is considering delaying omaveloxolone’s NDA pending completion of a second trial. That could push back approval by at least a year given that the target population, individuals with Friedreich’s ataxia, is limited and progression of the hard-to-treat illness is notoriously slow. The Covid-19 pandemic would also hinder Reata’s ability to complete an additional trial.