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.

John Reed at JPM 2019. Jeff Rumans for Endpoints News

Sanofi's John Reed con­tin­ues to re­or­ga­nize R&D, cut­ting 466 jobs while boost­ing can­cer, gene ther­a­py re­search

The R&D reorganization inside Sanofi is continuing, more than a year after the pharma giant brought in John Reed to head the research arm of the Paris-based company.
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The top 10 block­buster drugs in the late-stage pipeline — Eval­u­ate adds 6 new ther­a­pies to heavy-hit­ter list

Vertex comes in for a substantial amount of criticism for its no-holds-barred tactical approach toward wresting the price it wants for its commercial drugs in Europe. But the flip side of that coin is a highly admired R&D and commercial operation that regularly wins kudos from analysts for their ability to engineer greater cash flow from the breakthrough drugs they create.

Both aspects needed for success in this business are on display in the program backing Vertex’s triple for cystic fibrosis. VX-659/VX-445 + Tezacaftor + Ivacaftor — it’s been whittled down to 445 now — was singled out by Evaluate Pharma as the late-stage therapy most likely to win the crown for drug sales in 5 years, with a projected peak revenue forecast of $4.3 billion.

The latest annual list, which you can see here in their latest world preview, includes a roster of some of the most closely watched development programs in biopharma. And Evaluate has added 6 must-watch experimental drugs to the top 10 as drugs fail or go on to a first approval. With apologies to the list maker, I revamped this to rank the top 10 by projected 2024 sales, instead of Evaluate's net present value rankings.

It's how we roll at Endpoints News.

Here is a quick summary of the rest of the top 10:

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How small- to mid-sized biotechs can adopt pa­tient cen­tric­i­ty in their on­col­o­gy tri­als

By Lucy Clos­sick Thom­son, Se­nior Di­rec­tor of On­col­o­gy Pro­ject Man­age­ment, Icon

Clin­i­cal tri­als in on­col­o­gy can be cost­ly and chal­leng­ing to man­age. One fac­tor that could re­duce costs and re­duce bar­ri­ers is har­ness­ing the pa­tient voice in tri­al de­sign to help ac­cel­er­ate pa­tient en­roll­ment. Now is the time to adopt pa­tient-cen­tric strate­gies that not on­ly fo­cus on pa­tient needs, but al­so can main­tain cost ef­fi­cien­cy.

Neil Woodford. Woodford Investment Management via YouTube

Wood­ford braces po­lit­i­cal storm as UK fi­nan­cial reg­u­la­tors scru­ti­nize fund sus­pen­sion

The shock of Neil Wood­ford’s de­ci­sion to block with­drawals for his flag­ship fund is still rip­pling through the rest of his port­fo­lio — and be­yond. Un­der po­lit­i­cal pres­sure, UK fi­nan­cial reg­u­la­tors are now tak­ing a hard look while in­vestors con­tin­ue to flee.

In a re­sponse let­ter to an MP, the Fi­nan­cial Con­duct Au­thor­i­ty re­vealed that it’s opened an in­ves­ti­ga­tion in­to the sus­pen­sion fol­low­ing months of en­gage­ment with Link Fund So­lu­tions, which tech­ni­cal­ly del­e­gat­ed Wood­ford’s firm to man­age its funds.

Gilead baits new al­liance with $45M up­front, div­ing in­to the busy pro­tein degra­da­tion field

Gilead is jump­ing on board the pro­tein degra­da­tion band­wag­on. And they’re turn­ing to a low-pro­file Third Rock start­up for the ex­per­tise. But if you were look­ing for a trans­for­ma­tion­al deal to kick up fresh en­thu­si­asm for Gilead, you’ll have to re­main pa­tient.

This one will have a long way to go be­fore they get in­to the clin­ic.

The big biotech said Wednes­day morn­ing that it is pay­ing $45 mil­lion up­front and re­serv­ing a whop­ping $2.3 bil­lion in biotech bucks if San Fran­cis­co-based Nurix can point the way to new can­cer ther­a­pies, as well as drugs for oth­er, un­spec­i­fied dis­eases.

A new num­ber 1 drug? Keytru­da tapped to top the 10 biggest block­busters on the world stage by 2024

Analysts may be fretting about Keytruda’s longterm prospects as a host of rival therapies elbow their way to the market. But the folks at Evaluate Pharma are confident that last year’s $7 billion earner is headed for glory, tapping it to beat out the current #1 therapy Humira as AbbVie watches that franchise swoon over the next 5 years.

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In­vestor day prep at Mer­ck in­cludes a new strat­e­gy to pick up the pace on M&A — re­port

Mer­ck’s re­cent deals to buy up two bolt-on biotechs — Ti­los and Pelo­ton — weren’t an aber­ra­tion. In­stead, both ac­qui­si­tions mark a new strat­e­gy to beef up its dom­i­nant can­cer drug op­er­a­tions cen­tered on Keytru­da while look­ing to ad­dress grow­ing con­cerns that too many of its eggs are in the one I/O bas­ket for their PD-1 pro­gram. And Mer­ck is go­ing af­ter more small- and mid-sized buy­outs to calm those fears.

John Chiminski, Catalent CEO - File Photo

'It's a growth play': Catal­ent ac­quires Bris­tol-My­er­s' Eu­ro­pean launch pad, ex­pand­ing glob­al CD­MO ops

Catalent is staying on the growth track.

Just two months after committing $1.2 billion to pick up Paragon and take a deep dive into the sizzling hot gene therapy manufacturing sector, the CDMO is bouncing right back with a deal to buy out Bristol-Myers’ central launchpad for new therapies in Europe, acquiring a complex in Anagni, Italy, southwest of Rome, that will significantly expand its capacity on the continent.

There are no terms being offered, but this is no small deal. The Anagni campus employs some 700 staffers, and Catalent is planning to go right in — once the deal closes late this year — with a blueprint to build up the operations further as they expand on oral solid, biologics, and sterile product manufacturing and packaging.

This is an uncommon deal, Catalent CEO John Chiminski tells me. But it offers a shortcut for rapid growth that cuts years out of developing a green fields project. That’s time Catalent doesn’t have as the industry undergoes unprecedented expansion around the world.

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Arc­turus ex­pands col­lab­o­ra­tion, adding $30M cash; Ku­ra shoots for $100M raise

→  Rare dis­ease play­er Ul­tragenyx $RARE is ex­pand­ing its al­liance with Arc­turus $ARCT, pay­ing $24 mil­lion for eq­ui­ty and an­oth­er $6 mil­lion in an up­front as the two part­ners ex­pand their col­lab­o­ra­tion to in­clude up to 12 tar­gets. “This ex­pand­ed col­lab­o­ra­tion fur­ther so­lid­i­fies our mR­NA plat­form by adding ad­di­tion­al tar­gets and ex­pand­ing our abil­i­ty to po­ten­tial­ly treat more dis­eases,” said Emil Kakkis, the CEO at Ul­tragenyx. “We are pleased with the progress of our on­go­ing col­lab­o­ra­tion. Our most ad­vanced mR­NA pro­gram, UX053 for the treat­ment of Glyco­gen Stor­age Dis­ease Type III, is ex­pect­ed to move in­to the clin­ic next year, and we look for­ward to fur­ther build­ing up­on the ini­tial suc­cess of this part­ner­ship.”