No­var­tis punts a late-stage PI3K drug with a wor­ry­ing safe­ty pro­file to one of Chi­na’s up­start biotechs

Just months af­ter a group of re­searchers warned against the fur­ther de­vel­op­ment of a wor­ry­ing PI3K in­hibitor project No­var­tis had been work­ing on, the phar­ma gi­ant li­censed out the glob­al rights to a new­ly ac­tive Chi­nese biotech. 

No­var­tis is the lat­est in a long string of Big Phar­ma play­ers who have de­cid­ed to bow out of a trou­ble­some PI3K de­vel­op­ment pro­gram. But in­stead of drop­ping the drug the Swiss com­pa­ny hand­ed world­wide com­mer­cial rights to the late-stage bu­parlis­ib to one of Chi­na’s new up­start biotechs — rais­ing some thorny is­sues about how ques­tion­able drug as­sets may be passed to new play­ers for a com­mer­cial roll­out.

An­ge­lo Di Leo

Late last year a group of sci­en­tists pub­lished a re­port in The Lancet — fund­ed by No­var­tis — that con­clud­ed the drug’s safe­ty pro­file “does not sup­port its fur­ther de­vel­op­ment” in breast can­cer. The group was led by An­ge­lo Di Leo of Nuo­vo Os­pedale di Pra­to San­to Ste­fano in Pra­to, Italy.

The Chi­nese com­pa­ny is Ad­lai Nortye, based in Hangzhou. There’s no word on the terms here, but there has been a con­sid­er­able amount of mar­gin­al ef­fi­ca­cy and wor­ry­ing safe­ty da­ta on dis­play. 

In a study called Belle-3 which com­bined bu­parlis­ib with ful­ves­trant, re­searchers found that there was a pos­i­tive ben­e­fit in pro­gres­sion-free sur­vival: 3.9 months com­pared to 1.8 months for a mar­gin­al but sig­nif­i­cant ad­van­tage for pa­tients.

Grade 3/4 ad­verse events were re­port­ed in close to two out of three pa­tients in the drug arm, com­pared to 34% in the con­trol group. Se­ri­ous ad­verse events, though, were re­port­ed in 22% of the drug arm, com­pared to 16% in the con­trol group, with one treat­ment-re­lat­ed death to re­port in each arm. There were al­so three sui­cide at­tempts in the bu­parlis­ib group, rais­ing con­cerns about sui­ci­dal ideation among pa­tients ex­posed to the drug. Ruth O’Re­gan of the Uni­ver­si­ty of Wis­con­sin-Madi­son has raised con­cerns about the sui­cide at­tempts, not­ing that  “transam­i­nase el­e­va­tions and mood dis­or­ders in pa­tients on this drug may rep­re­sent a clin­i­cal­ly rel­e­vant chal­lenge.”

Ruth O’Re­gan

The re­searchers al­so not­ed in The Lancet that the work may have warned them off the drug for this set­ting, but con­clud­ed that “PI3K in­hibitors plus en­docrine ther­a­py in pa­tients with PIK3CA mu­ta­tions” is a promis­ing area of re­search.

The PI3K field has been plagued by safe­ty con­cerns and weak ef­fi­ca­cy. Roche dumped taselis­ib a few weeks ago at the end of a dis­ap­point­ing Phase III. Gilead’s pi­o­neer­ing Zy­delig got slapped with a black box warn­ing on se­ri­ous and some­times fa­tal tox­i­c­i­ties, forc­ing an end to its quest to com­plete front­line tri­als. Bay­er’s Aliqopa (co­pan­lis­ib) was ap­proved last fall for fol­lic­u­lar lym­phoma pa­tients, crowd­ing a field that Ve­rastem hopes to join with du­velis­ib, a PI3K dropped by In­fin­i­ty Phar­ma­ceu­ti­cals af­ter Ab­b­Vie walked away af­ter get­ting a glimpse of unim­pres­sive — but still ap­prov­able — re­sults. And now not­ed can­cer re­searcher Sid­dhartha Mukher­jee is be­gin­ning a hu­man study to de­ter­mine if a ke­to­genic di­et can close a feed­back loop that de­feats these drugs’ abil­i­ty to fight can­cer.

In its re­lease, Ad­lai Nortye doesn’t men­tion the breast can­cer study, or what kind of com­mer­cial prospects it has in an al­ready well de­vel­oped field. The com­pa­ny did, though, high­light “promis­ing ef­fi­ca­cy in com­bi­na­tion with pa­cli­tax­el in head and neck squa­mous cell car­ci­no­ma” and the fact that the drug “has re­ceived a Fast-Track des­ig­na­tion from the FDA.”

Brent Saunders [Getty Photos]

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An­a­lysts have been watch­ing this race for awhile now, as Sanofi/Re­gen­eron won a snap pri­or­i­ty re­view for what is now their third dis­ease in­di­ca­tion for this treat­ment. And they’re not near­ly done, build­ing up hopes for a ma­jor fran­chise.

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Ini­tial­ly pen­ciled in at a uni­corn-sized $225 mil­lion, the KKR-backed biotech has spiked that to the neigh­bor­hood of $300 mil­lion, look­ing to sell 20 mil­lion shares at $14 to $16 each. That’s an added 5 mil­lion shares, re­ports Re­nais­sance Cap­i­tal, which fig­ures the pro­posed mar­ket val­u­a­tion for Neil Ku­mar’s com­pa­ny at $1.8 bil­lion.

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Judge Leonard P. Stark is­sued a tem­po­rary in­junc­tion ear­li­er this week, forc­ing My­lan, Dr. Red­dy’s Lab­o­ra­to­ries and Au­robindo Phar­ma to shelve their launch plans to al­low the patent fight to pro­ceed. He ruled that al­low­ing the gener­ics in­to the mar­ket now would per­ma­nent­ly slash the price for No­var­tis, even if it pre­vails. 

Af­ter rais­ing $158M, this up­start's founders have star back­ers and plans to break new ground in gene ther­a­py

Back in 2014, Stephanie Tagliatela opted to take an early exit out of her PhD program after working in Mark Bear’s lab at MIT, where she specialized in the synaptic connections between neuronal cells in the brain. She never finished that PhD, but she and fellow MIT student Kartik Ramamoorthi — who was on the founding team at Voyager — came away with some ideas for a gene therapy startup.

Today, fully 5 years later, she and Ramamoorthi are taking the wraps off of a $104 million mega-round designed to take the cumulative work of their preclinical formative stage for Encoded Therapeutics into human studies. They’ve now raised $158 million since starting out in Illumina’s incubator in the Bay Area, and they believe they are firmly on track to do something unique in gene therapy.

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Novotech CEO Dr. John Moller

Novotech CRO Award­ed Frost & Sul­li­van Best Biotech CRO Asia-Pa­cif­ic 2019

Known in the in­dus­try as the Asia-Pa­cif­ic CRO, Novotech is now lead CRO ser­vices provider for the grow­ing num­ber of in­ter­na­tion­al biotechs se­lect­ing the re­gion for their stud­ies.

Re­flect­ing this Asia-Pa­cif­ic growth, Novotech staff num­bers are up 20% since De­cem­ber 2018 to 600 in-house clin­i­cal re­search peo­ple across a full range of ser­vices, across the re­gion.

Novotech’s ca­pa­bil­i­ties have been rec­og­nized by an­a­lysts like Frost & Sul­li­van, most re­cent­ly with the pres­ti­gious Asia-Pa­cif­ic CRO Biotech of the year award for best prac­tices in clin­i­cal re­search for biotechs for the fifth year. See oth­er awards here.

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The com­pa­ny’s shares $AC­ER cratered near­ly 77% to $4.47 in Tues­day morn­ing trad­ing.

Richard Gonzalez testifying in front of Senate Finance Committee, February 2019 [AP Images]

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Top an­a­lyst finds a sil­ver lin­ing in Ab­b­Vie’s $63B Al­ler­gan buy­out — but there’s a catch

Af­ter get­ting beat up on all sides from mar­ket ob­servers who don’t much care for the lat­est mega-deal to ar­rive in bio­phar­ma, at least one promi­nent an­a­lyst now is start­ing to like what he sees in the num­bers for Ab­b­Vie/Al­ler­gan.

But it’s go­ing to take some en­cour­age­ment if Ab­b­Vie ex­ecs want it to last.

Ab­b­Vie’s mar­ket cap de­clined $20 bil­lion on Tues­day as the stock took a 17% hit dur­ing the day. And SVB Leerink’s Ge­of­frey Porges can see a dis­tinct out­line of an up­side af­ter re­view­ing the fun­da­men­tals of the deal.

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