Re­searchers plot a course in­to PhI­II af­ter an­oth­er Alzheimer’s drug flunks a key test

Paul Aisen

An­oth­er big Alzheimer’s drug study has foundered in the clin­ic, but it’s be­ing po­si­tioned for Phase III in any case.

This time the fail­ure be­longs to Toya­ma Chem­i­cal, a sub­sidiary of Fu­ji­film, which wound up re­cruit­ing close to 500 pa­tients with a mild-to-mod­er­ate form of the dis­ease for the tri­al.

Ac­cord­ing to the com­pa­ny, the drug failed the pri­ma­ry end­point and the sec­on­daries, prov­ing un­able to do any bet­ter than a place­bo in im­prov­ing cog­ni­tion or func­tion. But, re­searchers say they tracked a ben­e­fit in a key bio­mark­er for tau on the high dose while spot­ting an im­prove­ment among ear­li­er-stage pa­tients in a post hoc analy­sis of the da­ta.

Back­ers of this drug be­lieve that it can in­flu­ence lev­els of tau as well as amy­loid be­ta, a one-two ther­a­py tar­get­ing two big cul­prits be­hind the dis­ease. And Toya­ma wants to take it in­to Phase III to find out how a bet­ter de­signed tri­al can work.

That has not proven to be a win­ning for­mu­la in the past, with 15 years of piv­otal fail­ures to prove it. But Toya­ma, like oth­ers in the field, be­lieve that what they have learned from their fail­ures can pave the way to suc­cess.

The study was launched by Paul Aisen back in 2014, well be­fore his group split away from UC San Diego and de­fect­ed to USC. Aisen has played a lead­ing role in some of the biggest flops in the busi­ness, in­clud­ing his out­spo­ken sup­port for Eli Lil­ly’s solanezum­ab, which failed a slate of late-stage stud­ies. Ac­cord­ing to Fu­ji­film, the orig­i­nal pre­clin­i­cal work on T-817MA was done by Rudy Tanzi, a Har­vard pro­fes­sor who claimed in 2014 to have fig­ured out a new ap­proach to re­search­ing Alzheimer’s drugs that would de­liv­er a win­ner in the clin­ic.

Tanzi him­self is the sci­en­tif­ic founder of Prana Biotech­nol­o­gy $PRAN, a tiny com­pa­ny with a mar­ket cap of on­ly $22 mil­lion that claimed to see great suc­cess in a failed Phase II study of a nov­el Alzheimer’s drug in­spired by Tanzi’s work on the role of zinc and cop­per bal­ances.

Tanzi re­spond­ed to our sto­ry in a com­ment:

For the record, I nev­er in any fo­rum pub­licly or pri­vate­ly “claimed to see great suc­cess on a failed Phase II” Alzheimer’s tri­al with PBT2. Per­haps you’re re­fer­ring to the Hunt­ing­ton’s dis­ease tri­al where I was im­pressed by the ef­fects of PBT2 on ex­ec­u­tive func­tion, while ac­knowl­edg­ing that the over­all tri­al failed. I will al­so say re­gard­ing Alzheimer’s dis­ease that I was en­cour­aged enough by the re­sults for PBT2 in low­er­ing se­nile plaque counts (in the treat­ment group) to con­tin­ue be­liev­ing, as I do to­day, that this drug may po­ten­tial­ly be use­ful for pre­vent­ing and treat­ing Alzheimer’s. It is cur­rent­ly on par­tial clin­i­cal hold by the FDA.

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.

Sanofi said in a state­ment that it is cut­ting its re­search ranks by 466 in France and Ger­many while drop­ping new, in-house car­di­ol­o­gy drug re­search. Ex­ist­ing car­dio pro­grams will go for­ward, says Sanofi, but the pipeline is be­ing cut off at the dis­cov­ery source. The phar­ma gi­ant, long known as a lag­gard in R&D, in­tends to com­mit more of its re­sources to the 4 re­main­ing R&D fo­cus­es: can­cer, im­munol­o­gy, rare dis­eases and vac­cines.

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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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.”

UP­DAT­ED: Chica­go biotech ar­gues blue­bird, Third Rock 'killed' its ri­val, pi­o­neer­ing tha­lassemia gene ther­a­py in law­suit

Blue­bird bio $BLUE chief Nick Leschly court­ed con­tro­ver­sy last week when he re­vealed the com­pa­ny’s be­ta tha­lassemia treat­ment will car­ry a jaw-drop­ping $1.8 mil­lion price tag over a 5-year pe­ri­od in Eu­rope — mak­ing it the plan­et’s sec­ond most ex­pen­sive ther­a­py be­hind No­var­tis’ $NVS fresh­ly ap­proved spinal mus­cu­lar at­ro­phy ther­a­py, Zol­gens­ma, at $2.1 mil­lion. A Chica­go biotech, mean­while, has been fum­ing at the side­lines. In a law­suit filed ear­li­er this month, Er­rant Gene Ther­a­peu­tics al­leged that blue­bird and ven­ture cap­i­tal group Third Rock un­law­ful­ly prised a vi­ral vec­tor, de­vel­oped in part­ner­ship with the Memo­r­i­al Sloan Ket­ter­ing Can­cer Cen­ter (MSK), from its grasp, and thwart­ed the de­vel­op­ment of its sem­i­nal gene ther­a­py.