Tau­Rx takes a slice of pos­i­tive da­ta and claims suc­cess af­ter a failed PhI­II Alzheimer’s study

Tau­Rx raised more than $225 mil­lion from some un­con­ven­tion­al fi­nanc­ing sources to back their big pair of Phase III stud­ies for a new drug to treat Alzheimer’s. And they trav­eled to the Alzheimer’s As­so­ci­a­tion’s con­fer­ence in Toron­to to ac­knowl­edge that the first study failed on both end­points.

But that’s not stop­ping the com­pa­ny from claim­ing a suc­cess.

Tau­Rx CEO Claude Wis­chik says that in­ves­ti­ga­tors tracked a pos­i­tive re­sponse in a sub­group of pa­tients tak­ing the tau in­hibitor LMTX as a monother­a­py. And while he con­cedes he has no firm idea why that group ben­e­fit­ed when most pa­tients tak­ing a com­bi­na­tion of the drug with stan­dard of care showed ab­solute­ly iden­ti­cal re­spons­es to the con­trol arm, Tau­Rx switched the end­points on their sec­ond Phase III study — just ahead of the da­ta lock — to the rel­a­tive­ly small num­ber of pa­tients on monother­a­py. And he says they came up with a pos­i­tive read­out that could pave the way to an ap­proval.

The tri­al re­sults, claims Wis­chik, are un­prece­dent­ed in demon­strat­ing an im­prove­ment on cog­ni­tion and func­tion for Alzheimer’s pa­tients.

“We have hit the pri­ma­ry end­points,” the CEO tells me. “Whether that will con­sti­tute ad­e­quate ev­i­dence for prod­uct ap­proval, we can’t say.”

In the first failed Phase III, Wis­chik says about 15% of the pa­tients in the study were on monother­a­py. In the sec­ond, it was 20% of the pa­tients. And while Wis­chik con­cedes that he’s bas­ing his claim on an analy­sis of a sub­group of pa­tients in both Phase II­Is, he goes on to re­ject the no­tion that it’s a sub­group analy­sis. Af­ter mov­ing the goal posts in the sec­ond study, he’s de­clar­ing a touch­down on the pri­ma­ry end­points for the new­ly switched fo­cus group of pa­tients.

Un­like sev­er­al of the most ad­vanced drugs in the clin­ic for Alzheimer’s fo­cused on amy­loid be­ta, Wis­chik has been an out­spo­ken sup­port­er of the tau the­o­ry, point­ing to a tox­ic clus­ter found in the brains of many pa­tients with the mem­o­ry eras­ing dis­ease. But his tau in­hibitor LMTX, in com­bi­na­tion with stan­dard ther­a­pies, failed to sep­a­rate out from the rate of de­cline in cog­ni­tion and func­tion tracked in the con­trol arm.

The da­ta backed up the com­pa­ny’s con­tention that tau is a “very promis­ing drug de­vel­op­ment path­way,” Wis­chik not­ed. But he al­so goes on to say that he doesn’t un­der­stand why the monother­a­py would work while the com­bo didn’t.

“It’s a weak­ness,” says Wis­chik, but not nec­es­sar­i­ly a fa­tal one.

If that con­fu­sion is shared by reg­u­la­tors, though, it could well scut­tle LMTX’s chances of any near-term ap­proval.

In case af­ter case, where a Phase III has end­ed in fail­ure on the pri­ma­ry end­points, the de­vel­op­er has had to go back to the draw­ing board and ei­ther de­sign a new pro­gram with back to back stud­ies, or throw in the tow­el.

In Eli Lil­ly’s case, that meant tak­ing years and hun­dreds of mil­lions of dol­lars to tack­le the amy­loid be­ta drug solanezum­ab again. Lil­ly al­so moved the goal posts, though, drop­ping func­tion as a pri­ma­ry end­point even though reg­u­la­tors are still in­sist­ing on see­ing clear ev­i­dence of ef­fi­ca­cy on cog­ni­tion and func­tion. Oth­ers, like Glax­o­SmithK­line, have walked away af­ter a fail­ure. In GSK’s case, their drug was picked up for $5 mil­lion by Ax­o­vant, which de­signed a new Phase III tri­al for a clear­ly de­fined sub­group. Alzheon is tak­ing much the same strat­e­gy.

“They can’t get it ap­proved with this,” says one de­vel­op­er ac­tive­ly en­gaged in the field.

In ad­di­tion to be­ing equal­ly puz­zled about the hy­poth­e­sis of why the drug would work in this one sub­group and not the rest, the de­vel­op­er not­ed that reg­u­la­tors would still in­sist on a new Phase III pro­gram be­fore al­low­ing any drug to be mar­ket­ed to a mass group of des­per­ate pa­tients.

The gold stan­dard in drug de­vel­op­ment re­mains a ran­dom­ized, con­trolled prospec­tive Phase III tri­al, and reg­u­la­tors are un­like­ly to start com­pro­mis­ing on that point now.

Based in Sin­ga­pore with re­search fa­cil­i­ties in Scot­land, Tau­Rx was al­ways the odd duck among the flock of com­pa­nies tack­ling Alzheimer’s. Un­con­ven­tion­al fi­nanc­ing from the Malaysian casi­no and re­sort op­er­a­tor Genting Group un­der­scored part of the unique pic­ture, and al­so rais­es ques­tions of how the com­pa­ny could go about fund­ing a new pair of Phase III stud­ies with 800 to 900 pa­tients, which could eas­i­ly cost an­oth­er $200 mil­lion.

Tau­Rx has raised ex­pec­ta­tions of a pos­si­ble IPO at some point, as com­pa­ny of­fi­cials say that the ab­sence of any drug that blunts Alzheimer’s could cre­ate an in­stant mar­ket worth $10 bil­lion a year for a pi­o­neer like it­self. But there have been plen­ty of oth­ers who tried the same thing, on­ly to be beat back in a decade of R&D ef­forts that have met with uni­ver­sal de­feat in the clin­ic over the past decade.

UP­DAT­ED: Roche bags 'break­through' an­ti-fi­bro­sis drug in $1.4B biotech buy­out deal

Roche is snapping up a “breakthrough” anti-fibrotic drug in a $1.4 billion buyout.

The pharma giant announced Friday that it is acquiring Promedior, primarily to get its hands on PRM-151, a recombinant form of human pentraxin-2 (PTX-2) protein that has nailed down mid-stage clinical data on idiopathic pulmonary fibrosis and demonstrating its potential for a range of fibrotic conditions.

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Amarin emerges from an ex­pert pan­el re­view with a clear en­dorse­ment for Vas­cepa and high odds of suc­cess when the FDA weighs in for­mal­ly

Several FDA experts who gathered Thursday to consider the landmark approval of Vascepa to reduce cardio events in an at-risk population voiced their unease about various aspects of the efficacy and safety data, or ultimately the population it should be used to treat. But the overwhelming belief that the data pointed to the drug’s benefit and clearly outweighed risks carried the day for Amarin.

The panel voted unanimously (16 to 0) to support the company’s positive data presentation — backing an OK for expanding the label to include reducing cardio risk. The vote points Amarin $AMRN down a short path to a formal decision by the FDA, with the odds heavily in its favor. Chances are the rest of the questions about the future of this drug will be hashed out in the label’s small print.

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No­var­tis spin­out’s first an­ti-ag­ing PhI­II is a flop, so now they’ll turn to Parkin­son’s chal­lenge as shares wilt

Novartis spinout resTORbio is grappling with the collapse of its lead clinical program this morning — an anti-aging R&D failure that will badly damage their rep in the field.

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No­var­tis scores its lat­est FDA OK — this time for a new sick­le cell dis­ease drug picked up in a $665M deal

Novartis’ decision to buy Oklahoma-based biotech Selexys 3 years ago for up to $665 million has paid off with an FDA approval today.

Blessed with the FDA’s breakthrough drug designation for a speedy review, the pharma giant has pinned down an approval for crizanlizumab, a new therapy designed to reduce the frequency of painful incidents of vaso-occlusive crises among sickle cell disease patients 16 or older.

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As­traZeneca gains EU nod for di­a­betes triple; Am­gen and Duke launch re­al-world PC­SK9 ob­ser­va­tion­al study

→ Weeks after winning EU approval to start marketing dapagliflozin as Forxiga, AstraZeneca has racked up another OK for a triplet combo involving the SGLT2 diabetes drug. Named Qtrilmet, the pill combines Forxiga with the DPP-4 inhibitor Onglyza (saxagliptin) and the bedrock drug metformin in a modified-release format. That 3-in-1 approach proved superior in reducing average blood glucose levels to a number of other dual combinations across 5 Phase III trials, including Forxiga plus metformin, Onglyza with metformin, or glimepiride with metformin.

Five drugs, in­clud­ing two No­var­tis ther­a­pies, win EMA en­dorse­ment

As is custom, an EMA panel on Friday issued its weekly recommendations on marketing applications submitted by drug developers. This week, the agency backed the use of five new therapies — including two Novartis drugs — but issued no negative reviews.

Novartis’ S1P drug for relapsing forms of multiple sclerosis (MS) drug, Mayzent (known chemically as siponimod), which was approved by the FDA in March — has been given the nod by the EMA. The Swiss drugmaker already sells its other MS drug, Gilenya, in both regions.

Atom­wise's X-37 spin­out gets $14.5 mil­lion to launch AI dis­cov­ery ef­forts

The folks behind Atomwise’s spinout X-37 like to think in cosmological metaphors, and you can think of their AI drug development model as probes sent into space from a central station. That station just got $14.5 million in Series A funding from DCVC Bio, Alpha Intelligence Capital and Hemi Ventures to back those missions.

X-37 uses Atomwise’s AI platform to identify drug targets and – unlike the parent company, which largely sticks to computers  – bring those into a wet lab and preclinical testing.  In addition to AI professionals, it’s led in by part by drug developers from Velocity Pharmaceutical Development.

Ab­bott Lab­o­ra­to­ries CEO Miles White pass­es ba­ton down to suc­ces­sor; Lon­za CEO Marc Funk hits the ex­it

→ Abbott Laboratories has named a successor to CEO Miles White after he announced that he was stepping down in March after 21 years of service. Robert Ford, the company’s COO and president, will take the helm. Ford is known for his work in the $25 billion merger between St. Jude Medical into Abbott in January 2017. White will remain with the company as executive chairman of the board. 

→ After snapping up Novartis’ Swiss facility, Novartis Center of Excellence, in July, Lonza has announced that their CEO, Marc Funk, is hitting the exit for “personal reasons.” Funk has been the CEO of the company for less than a year — brought onto the company back in March. In the meantime, chairman Albert Baehny will serve as interim CEO. 

BeiGene CEO John Oyler at an Endpoints event in Shanghai, October 2018 (Credit: Endpoints News/PharmCube)

UP­DAT­ED: In a first, FDA green-lights use of a Chi­nese built can­cer ther­a­py — and more are com­ing

Weeks after Amgen took a $2.7 billion stake in BeiGene, the Beijing-based biotech has secured its first-ever FDA approval for zanubrutinib, a BTK inhibitor, months ahead of schedule.

BeiGene’s drug, branded as Brukinsa, has secured accelerated approval for adult patients with mantle cell lymphoma (MCL) — a typically aggressive, rare, form of blood cancer — who have received at least one prior therapy.

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