No­var­tis just boast­ed of a big PhI­II PI3K suc­cess, but here’s why we should hold our ap­plause — for now

Just a few weeks af­ter No­var­tis $NVS punt­ed a po­ten­tial­ly dan­ger­ous PI3K drug out of its pipeline to a drug de­vel­op­er in Chi­na, the phar­ma gi­ant has come back with a pos­i­tive set of Phase III pro­gres­sion-free sur­vival da­ta on an­oth­er con­tender in this dicey can­cer drug field. And now No­var­tis says it will start knock­ing on reg­u­la­to­ry doors as it be­gins the ap­proval process.

Samit Hi­rawat

All we have in this first cut is the head­line ma­te­r­i­al: The drug hit on the PFS pri­ma­ry end­point, with a com­bi­na­tion of BYL719 (alpelis­ib) and ful­ves­trant out­per­form­ing ful­ves­trant alone in a sta­tis­ti­cal­ly sig­nif­i­cant fash­ion for “hor­mone-re­cep­tor pos­i­tive, hu­man epi­der­mal growth fac­tor re­cep­tor-2 neg­a­tive (HR+/HER2-) PIK3CA-mu­tant ad­vanced or metasta­t­ic breast can­cer that pro­gressed on or fol­low­ing aro­matase in­hibitor treat­ment with or with­out a CDK4/6 in­hibitor.”

Ad­verse events were “con­sis­tent” with oth­er stud­ies of this drug.

“BYL719 is the on­ly al­pha-spe­cif­ic PI3K in­hibitor and the first one to show po­ten­tial in­creased ben­e­fit and ac­cept­able tol­er­a­bil­i­ty for pa­tients,” said Samit Hi­rawat, No­var­tis’ head of on­col­o­gy glob­al drug de­vel­op­ment.

We won’t see the da­ta un­til a lat­er con­fer­ence, but some an­a­lysts are al­ready as­sign­ing block­buster sales fore­casts for the drug. 

“We es­ti­mate alpelis­ib peak sales po­ten­tial at $1.9 bil­lion, and lift our prob­a­bil­i­ty of suc­cess to 80%,” said Bruno Bu­lic, an an­a­lyst at Baad­er Helvea, ac­cord­ing to a Reuters re­port.

But let’s step back for a sec­ond. We’ve seen plen­ty of bull­ish fore­casts for ex­per­i­men­tal PI3K drugs, and the harsh re­al­i­ty has nev­er lived up to the hype.

As a field, PI3K re­search has been more of a dis­as­ter zone than block­buster pro­duc­er. 

Roche dumped taselis­ib at the end of a dis­ap­point­ing Phase III, af­ter pos­i­tive but weak PFS da­ta failed to over­come a chancy risk pro­file. The Roche set­back un­der­scored the weak dura­bil­i­ty of the PI3K class that has tem­pered en­thu­si­asm in re­cent years. 

Gilead’s pi­o­neer­ing Zy­delig, mean­while, 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 as Ab­b­Vie walked away af­ter get­ting a glimpse of unim­pres­sive — but still ap­prov­able — re­sults. 

Then there’s bu­parlis­ib, an­oth­er No­var­tis pro­gram. The phar­ma gi­ant dis­patched the drug to Ad­lai Nortye in an out­li­cens­ing deal in June, but on­ly af­ter re­searchers raised a red safe­ty flag warn­ing to the com­pa­ny that the safe­ty pro­file is so trou­bling that it doesn’t “sup­port its fur­ther de­vel­op­ment” in breast can­cer.

Now not­ed can­cer re­searcher Sid­dhartha Mukher­jee is be­gin­ning a hu­man study to de­ter­mine if a ke­to­genic di­et can close an in­sulin feed­back loop that de­feats these drugs’ abil­i­ty to fight can­cer.

So while the head­line ma­te­r­i­al looks good, the re­al sto­ry about this drug’s fu­ture will lie in the de­tails, which we don’t have yet. No­var­tis is off to a good start, but the third act of this R&D epic is still in front of us.

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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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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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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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.

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.

UP­DAT­ED: Es­ti­mat­ing a US price tag of $5K per course, remde­sivir is set to make bil­lions for Gilead, says key an­a­lyst

Data on remdesivir — the first drug shown to benefit Covid-19 patients in a randomized, controlled trial setting — may be murky, but its maker Gilead could reap billions from the sales of the failed Ebola therapy, according to an estimate by a prominent Wall Street analyst. However, the forecast, which is based on a $5,000-per-course US price tag, triggered the ire of one top drug price expert.