Ax­o­vant races to PhI­II de­men­tia study as nelotanserin clears an ear­ly hur­dle, but ques­tions linger

Vivek Ra­maswamy

Ax­o­vant says that its drug nelotanserin has cleared an ear­ly hur­dle in a Phase II study for Lewy body de­men­tia, trig­ger­ing a de­ci­sion to ex­pand the mid-stage tri­al and hit­ting the green light for a Phase III to get start­ed lat­er this year. But in­vestors are like­ly to ques­tion a stum­ble on key sec­ondary goals.

A snap­shot of re­sults for the first tiny group of 11 pa­tients con­clud­ed that they were demon­strat­ing sta­tis­ti­cal­ly sig­nif­i­cant re­spons­es to the drug on the pri­ma­ry end­point. These pa­tients in­clud­ed peo­ple suf­fer­ing from Parkin­son’s as well as Lewy body de­men­tia. They were re­cruit­ed af­ter suf­fer­ing from fre­quent vi­su­al hal­lu­ci­na­tions.

“The pri­ma­ry out­come mea­sures of the study were ex­trapyra­mi­dal signs as as­sessed by Uni­fied Parkin­son’s Dis­ease Rat­ing Scale (UP­DRS) Parts II + III and safe­ty,” the com­pa­ny re­port­ed.

There was a big hitch, though. The tri­al did not hit sec­ondary end­points laid out by in­ves­ti­ga­tors to track the fre­quen­cy of vi­su­al hal­lu­ci­na­tions, in­clud­ing both a stan­dard SAPS as­sess­ment as well as an end­point they cre­at­ed in­ter­nal­ly at Ax­o­vant. And that may have weighed in on in­vestors’ re­sponse to the re­sults, with Ax­o­vant’s stock up on­ly 5% in pre-mar­ket trad­ing.

Ax­o­vant, the first of Vivek Ra­maswamy’s biotechs to get start­ed, plans to hus­tle in­to the ex­pand­ed Phase II for the drug — a 5HT2A an­tag­o­nist — as it wastes no time in get­ting the Phase III up and run­ning. Ra­maswamy has made no se­cret of his plans to ac­cel­er­ate R&D at his com­pa­nies. And Ax­o­vant is the most ad­vanced with a big tri­al un­der­way for Alzheimer’s.

Ax­o­vant al­ready faces an es­tab­lished mar­ket play­er. Aca­dia’s ri­val drug Nu­plazid won FDA ap­proval for Parkin­son’s de­men­tia last spring, but on­ly af­ter reg­u­la­tors ex­pressed their safe­ty con­cerns, not­ing a dis­tinct in­crease in the num­ber of deaths as well as the rate of ad­verse events among the pa­tients tak­ing the drug com­pared to the con­trol arm of the study — even if there was no ob­vi­ous clue what was trig­ger­ing those events.

Ax­o­vant’s hope is that it can come out of clin­i­cal tri­als with a bet­ter suc­cess rate and a clean­er safe­ty pro­file as both com­pa­nies tar­get a broad pa­tient pop­u­la­tion suf­fer­ing from dif­fer­ent forms of de­men­tia.

“I am in­trigued by the ben­e­fits ob­served on the UP­DRS in this study,” stat­ed Dr. James Lev­erenz, Chair, Sci­en­tif­ic Ad­vi­so­ry Coun­cil of the Lewy Body De­men­tia As­so­ci­a­tion and Di­rec­tor of the Cleve­land Lou Ru­vo Cen­ter for Brain Health at the Cleve­land Clin­ic. “If a sin­gle drug could si­mul­ta­ne­ous­ly ad­dress the mo­tor and neu­ropsy­chi­atric symp­toms of Lewy body de­men­tia, which the pub­lished lit­er­a­ture sug­gests may be the case for 5HT2A an­tag­o­nists, it would rep­re­sent a unique and im­por­tant ad­vance for the treat­ment of this con­di­tion. I look for­ward to re­view­ing the full dataset lat­er this year.”

Com­mu­ni­cat­ing the val­ue of pre­ci­sion med­i­cine

By Natasha Cowan, Content Marketing Manager at Blue Latitude Health.
Many stakeholders are confused by novel precision medicines, including patients and healthcare professionals. So, how can industry help them to navigate this complexity?

Precision medicine represents a new paradigm in healthcare. It embodies the shift from treating many patients with the same therapy, to having the tools to identify the best treatment for every patient.

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Avalon Ventures chief Jay Lichter has a well-known yen for drug development programs picked up in academia. And what he found in Haoxing Xu’s lab at the University of Michigan pricked his interest enough to launch one of his umbrella biotechs in San Diego.
Xu’s work laid the foundation for Avalon to launch Calporta, which has been working on finding small molecule agonists of TRPML1 (transient receptor potential cation channel, mucolipin subfamily, member 1) for lysosomal storage disorders. And that pathway, they believe, points to new approaches on major market neurodegenerative diseases like Parkinson’s, ALS and Alzheimer’s.

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In­vestors could emerge from Neil Wood­ford de­ba­cle with £1B loss, in­ter­nal analy­sis re­veals

When Link Fund Solutions announced that it is closing Woodford Equity Income Fund permanently and kicking out Neil Woodford, it was implied that investors probably won’t get back everything they entrusted to the fund manager. But nobody knew just how much they would lose.

An internal analysis commissioned by Link suggested that the collective loss could amount to £1 billion — out of a fund last valued at £3.1 billion — Citywire has revealed.

GSK's asth­ma bi­o­log­ic Nu­cala scores in rare blood dis­or­der study

GlaxoSmithKline’s asthma drug Nucala, which received a resounding FDA rejection for use in chronic obstructive pulmonary disease (COPD) last year, has shown promise in a rare blood disorder.

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Spe­cial re­port: Twen­ty ex­tra­or­di­nary women in bio­phar­ma R&D who worked their way to the top

What differentiates a woman leader in biopharma R&D from a man?

Not much, except there are fewer of them in senior posts. Data suggest women are not more risk-averse, family-oriented or less confident than their male counterparts — indeed the differences between the two sexes are negligible. But a glance at the top R&D positions in Big Pharma leaves little doubt that upward migration in the executive ranks of biopharma R&D is tough.

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FDA Vas­cepa re­view spot­lights new safe­ty sig­nals, pos­si­ble min­er­al oil spoil­er as Amarin hunts a block­buster ap­proval

An in-house FDA review of Amarin’s Vascepa raises a set of hurdles the biotech will have to clear if the biotech expects to get the long-awaited FDA approval that could set it on a path to superstar status. But it appears that Amarin has survived another potential setback without introducing a major new threat to its prospects.

The stakes don’t get much higher, with analysts saying a win this week for Amarin could lead to billions in new sales — provided the agency stamps it with an OK. And investors liked what they say in the FDA review this morning, bumping the stock $AMRN 17%.

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FDA puts Sol­id Bio’s lead gene ther­a­py pro­gram on hold — again — af­ter an­oth­er pa­tient is hurt by SGT-001

Solid Biosciences continues to be plagued by safety issues.

Close to 18 months after the gene therapy biotech was able to quickly shed an FDA hold on their lead Duchenne muscular dystrophy program for SGT-001, regulators have stepped back in to force another halt after another patient was hit hard by a set of serious adverse events remarkably similar to the first set.

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FDA slaps a hold on an AML tri­al as Mark­er scraps a fail­ing ovar­i­an can­cer pro­gram, sink­ing shares

The FDA has placed a hold on a Phase II AML trial from the small immuno-oncology biotech Marker Therapeutics. Marker disclosed the issue two weeks after responding to FDA concerns, adding it to the Q3 release Tuesday. The company also announced it was scrapping a Phase II ovarian cancer program it determined was unlikely to succeed.

The agency’s concern centers around two reagents used in manufacturing for their trial for acute myeloid leukemia patients who have received a stem cell transplant. The reagents are from third parties and not present in the final product, Marker said.

Eli Lil­ly-backed biotech grabs $100M to dis­patch an­ti­body-oligonu­cleotide con­ju­gates af­ter mus­cu­lar dy­s­tro­phy

Hold up your hand. Make a fist. Now open it. And again.

If you can do it fully and with ease, then the proteins in your hand are likely working properly. If you can’t then they may not be. In people with myotonic muscular dystrophy, something more atomic is going on.

In those folks, the problem is RNA. Certain base pairs repeat far beyond normal, up to 11,000 superfluous letters in some cases. The extended strands form “clumps.” Proteins misform and can’t function properly. They often allow one movement but not the reverse, a condition called myotonia that gives the dystrophy its name.