No OS ben­e­fit? No prob­lem. FDA pan­el backs use of Lyn­parza in pan­cre­at­ic can­cer

As As­traZeneca works to tight­en its hold on the PARP mar­ket, an in­de­pen­dent pan­el of ad­vi­sors to the FDA cau­tious­ly en­dorsed Lyn­parza’s use in cer­tain pan­cre­at­ic can­cer pa­tients, even though it failed to help pa­tients live longer.

On Tues­day, pan­elists vot­ed 7-5 to rec­om­mend the drug for main­te­nance use in pa­tients with germline BR­CA-mu­tat­ed metasta­t­ic ade­no­car­ci­no­ma of the pan­creas, whose dis­ease has not pro­gressed on at least 16 weeks of first-line plat­inum-based chemother­a­py. Glob­al­ly, germline BR­CAm pan­cre­at­ic can­cer ac­counts for 5-7% of all cas­es.

The FDA is not oblig­ed to ac­cept the rec­om­men­da­tions of the pan­el but typ­i­cal­ly does. The agency is ex­pect­ed to make its fi­nal de­ci­sion in the fourth quar­ter.

Lyn­parza, known chem­i­cal­ly as ola­parib, is al­ready ap­proved as a main­te­nance agent in mul­ti­ple lines of ther­a­py for ovar­i­an can­cer, as well as a metasta­t­ic breast can­cer ther­a­py. It is al­so ex­pect­ed to se­cure ap­proval in prostate can­cer next year.

The pan­cre­at­ic can­cer ap­pli­ca­tion was based on the 154-pa­tient, place­bo-con­trolled PO­LO tri­al. Lyn­parza in­duced a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in pro­gres­sion-free sur­vival (PFS) (95% con­fi­dence in­ter­val: 0.35, 0.81; p=0.0035) — cor­re­spond­ing to a 3.6-month im­prove­ment in me­di­an PFS. There was al­so ev­i­dence of tu­mor shrink­age, in­di­cat­ed by the dif­fer­ence in the over­all re­sponse rate of 9.9% ver­sus the place­bo arm. How­ev­er, no ef­fect on over­all sur­vival (OS) was ob­served.

In a brief­ing doc­u­ment post­ed days ear­li­er, FDA staff high­light­ed their con­cerns about the drug’s use in this pan­cre­at­ic can­cer pop­u­la­tion. Re­view­ers took is­sue that the pri­ma­ry end­point was as­sessed on the ba­sis of tu­mor mea­sure­ments, which can dif­fer among tu­mor set­tings and are sub­ject to as­sess­ment bias. In ad­di­tion, they ques­tioned whether the tri­al was ‘ad­e­quate­ly con­trolled’ giv­en its small size. An­oth­er source of un­cer­tain­ty, they said, was the lim­i­ta­tions of cur­rent imag­ing tech­nol­o­gy to ac­cu­rate­ly mea­sure the ef­fect on PFS.

“Giv­en these con­cerns re­gard­ing the ac­cu­ra­cy of tu­mor mea­sure­ment in pan­cre­at­ic can­cer, FDA ap­proval of all pre­vi­ous drugs for the treat­ment of pan­cre­at­ic can­cer has been based on ef­fects on OS, an end­point for which as­sess­ment bias and lim­i­ta­tions in the ac­cu­ra­cy of tu­mor mea­sure­ment by imag­ing tech­nol­o­gy are not present,” the re­port said.

“FDA ac­knowl­edges that a dif­fer­ence in PFS fa­vor­ing the ola­parib arm has been demon­strat­ed in the PO­LO tri­al. How­ev­er, there is un­cer­tain­ty that the ob­served mag­ni­tude of the treat­ment ef­fect on PFS ac­cu­rate­ly rep­re­sents the true treat­ment ef­fect…”

As­traZeneca and part­ner Mer­ck’s Lyn­parza, akin to GSK’s Ze­ju­la and Clo­vis On­col­o­gy’s Rubra­ca, is a poly-ADP ri­bose poly­merase (PARP) in­hibitor. 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.

“While there are cur­rent­ly 4 ap­proved PARP in­hibitors in the US and Eu­rope, As­traZeneca and part­ner Mer­ck have es­tab­lished the drug as the mar­ket leader through a com­bi­na­tion of mar­ket­ing ex­per­tise and strate­gic tri­al de­signs,” SVB Leerink’s An­drew Berens wrote in a note last month.

“We ex­pect the drug to re­main the mar­ket leader…with po­ten­tial ex­pan­sion to oth­er tu­mors like pan­cre­at­ic, blad­der and lung,” he said, adding that ex­perts ex­pect Lyn­parza to con­tin­ue as the dom­i­nant PARP in­hibitor un­til its loss of ex­clu­siv­i­ty, which is mod­eled for 2029.

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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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.

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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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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FDA de­lays de­ci­sion on No­var­tis’ po­ten­tial block­buster MS drug, wip­ing away pri­or­i­ty re­view

So much for a speedy review.

In February, Novartis announced that an application for their much-touted multiple sclerosis drug ofatumumab had been accepted and, with the drug company cashing in on one of their priority review vouchers, the agency was due for a decision by June.

But with June less than 48 hours old, Novartis announced the agency has extended their review, pushing back the timeline for approval or rejection to September. The Swiss pharma filed the application in December, meaning their new schedule will be nearly in line with the standard 10-month window period had they not used the priority voucher.

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Mer­ck wins a third FDA nod for an­tibi­ot­ic; Mereo tack­les TIG­IT with $70M raise in hand

Merck — one of the last big pharma bastions in the beleaguered field of antibiotic drug development — on Friday said the FDA had signed off on using its combination drug, Recarbrio, with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. The drug could come handy for use in hospitalized patients who are afflicted with Covid-19, who carry a higher risk of contracting secondary bacterial infections. Once SARS-CoV-2, the virus behind Covid-19, infects the airways, it engages the immune system, giving other pathogens free rein to pillage and plunder as they please — the issue is particularly pertinent in patients on ventilators, which in any case are breeding grounds for infectious bacteria.