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.

Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,700+ biopharma pros reading Endpoints daily — and it's free.

Novartis CEO Vas Narasimhan [via Bloomberg/Getty]

I’m not per­fect: No­var­tis chief Vas Narasimhan al­most apol­o­gizes in the wake of a new cri­sis

Vas Narasimhan has warily stepped up with what might pass as something close to a borderline apology for the latest scandal to engulf Novartis.

But he couldn’t quite get there.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,700+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: Pay­back? An­a­lysts say Sarep­ta was blind­sided by an FDA re­jec­tion dri­ven by reg­u­la­to­ry re­venge

In one of the least anticipated moves of the year, the FDA has rejected Sarepta’s application for an accelerated approval of its Duchenne MD drug golodirsen after fretting over safety issues.

In a statement that arrived after the bell on Monday, Sarepta explained the CRL, saying:

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,700+ biopharma pros reading Endpoints daily — and it's free.

FDA de­ci­sion on Ver­tex's CF triple will come just ahead of planned CEO shake­up

Vertex has clinched a priority review for the all-important cystic fibrosis triple that will blaze the trail for treating a large group of patients unhelped by its current drugs.

FDA regulators have set a PDUFA date of March 19, 2020, just a year after the Boston biotech posted positive Phase III results showing that people with two F508del mutations experienced statistically significant improvements in lung function after a 4-week regimen of VX-445, tezacaftor and ivacaftor. After reviewing 24-week data among patients with one F508del mutation and one minimal function mutation — and thoroughly comparing the VX-445 triple with another combo featuring VX-659 on scores like safety, drug-drug interactions, and photosensitivity — Vertex ultimately went with VX-445.

An MIT spin­out kills one of its ‘liv­ing ther­a­peu­tics’ af­ter flunk­ing an ear­ly-stage study — shares rout­ed

Just a few weeks after bagging $80 million in a deal to collaborate with Gingko Bioworks on its special blend of engineered bacteria used for “living therapeutics,” little Synlogic in Boston $SYBX is tossing one of its two clinical programs after watching an early-stage study go down in defeat.

Their Phase Ib/IIa study for SYNB1020 to counter the accumulation of ammonia in the body, a condition called hyperammonemia or urea cycle disorder, floundered at the interim readout, forcing the biotech to kill it and reserve its cash for pipeline therapies with greater potential.

Elan­co to buy Bay­er's an­i­mal health busi­ness for $7.6B, as deal­mak­ing gath­ers steam in the sec­tor

Last week, Elanco explicitly dodged answering questions about its rumored interest in Bayer’s animal health business in its post-earnings call. On Tuesday, the Eli Lilly spinoff disclosed it was purchasing the German drug maker’s veterinary unit in a cash-and-stock deal worth $7.6 billion. 

Elanco $ELAN has been busy on the deal-making front. In April, it laid out plans to swallow its partner, Kansas-based pet therapeutics company Aratana $PETX. A July report by Reuters suggested a potential Bayer deal was being explored, and Bloomberg last week said the deal was imminent, citing sources. 

As­traZeneca's di­a­betes drug Farx­i­ga helps pa­tients with heart dis­ease and with­out di­a­betes in land­mark tri­al

Months ago, data on J&J’s $JNJ Invokana indicated the diabetes drug conferred cardiovascular (CV) benefit in patients who do and do not have preexisting CV disease. On Tuesday, AstraZeneca’s $AZN rival treatment, Farxiga, was shown to cut the risk of CV death or the worsening of heart failure in patients with heart disease, in a landmark trial.

The treatments, in addition to Jardiance from Eli Lilly $LLY, belong to a class of diabetes drugs called sodium-glucose co-transporter 2 (SGLT2) inhibitors, which work by curbing the absorption of glucose via the kidneys so that surplus glucose is excreted through urination.

Levi Garraway. Broad Institute via Youtube

Roche raids Eli Lil­ly for its next chief med­ical of­fi­cer as San­dra Horn­ing plans to step down

We found out Monday morning where Levi Garraway was headed after he left Eli Lilly as head of oncology R&D a few days ago. Roche named Garraway as their new chief medical officer, replacing Sandra Horning, who they say is retiring from the company.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,700+ biopharma pros reading Endpoints daily — and it's free.

Af­ter a posse of Wall Street an­a­lysts pre­dict a like­ly new win for Sarep­ta, we're down to the wire on a crit­i­cal FDA de­ci­sion

As Bloomberg notes, most of the Wall Street analysts that cover Sarepta $SRPT are an upbeat bunch, ready to cheer on the team when it comes to their Duchenne MD drugs, or offer explanations when an odd setback occurs — as happened recently with a safety signal that was ‘erroneously’ reported last week.

Ritu Baral Cowen
Endpoints News

Basic subscription required

Unlock this story instantly and join 57,700+ biopharma pros reading Endpoints daily — and it's free.