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.”

Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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A new chap­ter in the de­cen­tral­ized clin­i­cal tri­al ap­proach

Despite the promised decentralized trial revolution, we haven’t yet moved the needle in a significant way, although we are seeing far bolder commitments to this as we continue to experience the pandemic restrictions for some time to come. The vision of grandeur is one thing, but operationalizing and execution are another and recognising that change, particularly mid-flight on studies, is worthy of thorough evaluation and consideration in order to achieve success. Here we will discuss one of the critical building blocks of a Decentralized and Remote Trial strategy: TeleConsent; more than paper under glass, it is a paradigm change and key digital enabler.

John Maraganore, Alnylam CEO (Scott Eisen/Bloomberg via Getty Images)

With lumasir­an on the FDA's doorstep, Al­ny­lam reads out new PhI­II da­ta in PH1

Just over a month away from its December PDUFA date, Alnylam flaunted new data from two Phase III studies to back lumasiran in primary hyperoxaluria type 1 (PH1), a rare liver condition.

The Cambridge, MA-based biotech snagged a priority review for the candidate back in June, and got positive feedback from the EMA’s Committee for Medicinal Products for Human Use just last week. Lumasiran uses RNA interference (RNAi) to silence the gene for glycolate oxidase, an enzyme used in the production of oxalate.

Stephen Hoge, Moderna president (Moderna)

On morn­ing of FDA Covid-19 ad­comm, Mod­er­na com­pletes PhI­II en­roll­ment, putting them neck-and-neck with Pfiz­er

Weeks away from a potential EUA application, Moderna announced they have completed enrollment in their 30,000-person Phase III Covid-19 vaccine trial, with over a third of volunteers non-white and a quarter over the age of 65.

The announcement caps what has been the most closely-watched recruitment race in the history of drug development, as Pfizer and Moderna rushed to get enough volunteers to prove whether or not experimental vaccines could actually protect people from contracting Covid-19. Pfizer reached that mark on Sept. 15. Moderna said around the same time that they would slow down enrollment to ensure they enrolled enough participants from minority and at-risk groups.

Pfiz­er scoops up an an­tibi­ot­ic in rare M&A deal, bag­ging a vir­tu­al start­up op­er­at­ing on a shoe­string bud­get

Pfizer is stepping up with a rare antibiotics buyout deal today, grabbing Palo Alto, CA-based Arixa Pharmaceuticals in a bid to add a new oral version of avibactam, a beta lactamase inhibitor — or BLI — approved back in 2015 as part of the IV treatment Avycaz.

The Arixa acquisition follows some encouraging Phase I responses demonstrating that 60% to 80% of the oral drug is absorbed into the bloodstream. Only 7% of the IV version is absorbed orally, far below the 30% threshold Arixa has pointed to as a therapeutic threshold. The buyout gives Pfizer’s hospital group a line on a new oral combo with antibiotics like ceftibuten to go after drug-resistant cases of urinary tract infections and other ailments.

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News brief­ing: UK biotech 4D phar­ma heads for Nas­daq via SPAC; Dr. Red­dy's shuts down man­u­fac­tur­ing af­ter cy­ber­at­tack

Another pharma company is intending to use a SPAC to join the Nasdaq.

4D pharma, a UK-based biotech, is reverse-merging with a blank check company in a deal worth up to $37.6 million. The move will give 4D pharma a new Nasdaq ticker, which will be $LBPS, using the American Depositary Share program. 4D will continue to trade on the London stock exchange under its previous ticker.

As a result of the move, 4D pharma will gain $14.6 million in cash held by the blank check company, dubbed Longevity $LOAC. The merger is expected to be completed in early 2021, after which shares will be immediately tradeable on Nasdaq.

Can B cells break the bound­aries of cell ther­a­py? Long­wood start­up has $52M to prove a new en­gi­neer­ing tech

Back in December 2017, as the cell therapy world was still basking in the virtually back-to-back approvals of two pioneering CAR-Ts, researchers at Seattle Children’s Research Institute reported a scientific first in a different corner of the field: engineer B cells to treat disease.

The team, led by David Rawlings and Richard James, eventually worked with Longwood Fund to start a biotech around those findings. And now Atlas Venture and RA Capital Management are coming on board to lead a $52 million launch round, joined by Alta Partners, for Be Biopharma.

Bo Cumbo, AavantiBio CEO (file photo)

Bo Cum­bo jumps from the top com­mer­cial post at Sarep­ta to the helm of a gene ther­a­py start­up with some in­flu­en­tial back­ers, big plans and $107M

After a 7-year stretch building the commercial team at Sarepta, longtime drug salesman Bo Cumbo is jumping to the entrepreneurial side of the business, taking the helm of a startup that’s got several deep-pocket investors. And he’s not just bringing his experience in selling drugs.

He tells me that when he told Sarepta CEO Doug Ingram about it, his boss got excited about the venture and opted to jump in with a $15 million investment from Sarepta to add to the launch money, alongside 3 of the busiest investors in biotech.

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HHS secretary Alex Azar (at the podium) and FDA commissioner Stephen Hahn (Pete Marovich/Getty Images)

Covid-19 roundup: Azar open­ly plan­ning Hahn ouster — re­port; Vul­ner­a­ble pop­u­la­tions like­ly to get vac­cines by Jan­u­ary

The relationship between HHS secretary Alex Azar and FDA commissioner Stephen Hahn has deteriorated to the point where Azar has suggested replacing Hahn, according to a Politico report.

Azar was angered by the FDA’s pushback of the Trump administration’s proposals for authorizing Covid-19 vaccines, so much so that he began openly floating potential replacements for Hahn. The report cited six unnamed sources that said Azar discussed bringing up Hahn’s removal to the White House.

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