Jean-Paul Clozel, Idorsia CEO (Patrick Straub/Keystone via AP Images)

Sec­ond PhI­II study for Idor­si­a's sleep drug re­turns pos­i­tive re­sults, but al­so rais­es new ques­tions

Fol­low­ing a suc­cess­ful Phase III study in April show­cas­ing the safe­ty and po­ten­tial of its new sleep drug, Idor­sia post­ed some mixed news in the sec­ond Phase III study, but that won’t stop a planned fil­ing aimed at reg­u­la­to­ry ap­proval.

The drug, a dual orex­in re­cep­tor an­tag­o­nist (DO­RA) called dari­dorex­ant, was found to sig­nif­i­cant­ly im­prove sleep main­te­nance and sub­jec­tive to­tal sleep time in 25 mg dos­es, repli­cat­ing re­sults from the first Phase III study. How­ev­er, im­prove­ments in sleep on­set and day­time func­tion­ing nar­row­ly missed sta­tis­ti­cal sig­nif­i­cance, de­spite nu­mer­i­cal con­sis­ten­cy with the April study.

Idor­sia al­so test­ed 10 mg dos­es of dari­dorex­ant in the study and found pos­i­tive re­sponse across all four ef­fi­ca­cy mea­sures, but all fell short of be­ing sta­tis­ti­cal­ly sig­nif­i­cant.

The new study mea­sured dari­dorex­ant’s ef­fects in 924 adult and el­der­ly pa­tients. Side ef­fects from the tests re­mained low, as with the first study, with se­ri­ous in­stances re­main­ing bal­anced across dosage amounts and place­bos, ac­cord­ing to the biotech.

Re­sults from the two stud­ies re­gard­ing the 25 mg dos­es and place­bos will now be pooled, and some an­a­lysts ex­pect this will of­fer a promis­ing pro­file to take to reg­u­la­tors. Ques­tions will like­ly re­main, how­ev­er, giv­en the cau­tion that reg­u­la­tors usu­al­ly take when ap­prov­ing in­som­nia treat­ments.

Pe­ter Welford at Jef­feries sees the poor re­sults for the low dose as a good thing, as it re­moves any temp­ta­tion the FDA may have to for­go the high dose and go with the less threat­en­ing low­er dose — as they did with Mer­ck. But its suc­cess is still no sure thing.

Im­por­tant­ly the low­er 10mg dose showed small­er non-sig­nif­i­cant ben­e­fits, re­mov­ing the risk reg­u­la­tors en­dorse a sub­op­ti­mal dose to err on the side of cau­tion, in our view. Com­mer­cial un­cer­tain­ties re­main.

In­som­nia drugs gen­er­al­ly are slow to be­come avail­able and are dif­fi­cult to pro­duce. The drugs are al­so heav­i­ly reg­u­lat­ed, as the FDA demon­strat­ed when it im­posed black box warn­ings last year on a slew of more com­mon­ly-known drugs like Lunes­ta, Am­bi­en and Sonata.

Where DO­RAs dif­fer from tra­di­tion­al in­som­nia drugs is in the in­hi­bi­tion of orex­in sig­nal­ing. Orex­ins, dis­cov­ered in 1998, are hor­mones pro­duced by the hy­po­thal­a­mus that reg­u­late sleep, arousal and ap­petite.

On­ly two DO­RAs have hit the mar­ket in the US, but they al­so faced up­hill climbs. Mer­ck’s Bel­som­ra (chem­i­cal­ly known as su­vorex­ant), re­leased in 2014, re­quired warn­ing la­bels re­gard­ing next-day resid­ual ef­fects and abuse po­ten­tial, among oth­er safe­ty risks.

Ad­di­tion­al­ly, Ei­sai’s DO­RA Dayvi­go (lem­borex­ant) scored an FDA ap­proval in De­cem­ber and launched last month but al­so need­ed sim­i­lar warn­ings.

Idor­sia spun off of Swiss phar­ma com­pa­ny Acte­lion af­ter a $30 bil­lion ac­qui­si­tion by John­son & John­son in ear­ly 2017. Idor­sia had been Acte­lion’s old re­search and de­vel­op­ment de­part­ment and is head­ed up by Acte­lion’s founder and CEO, Jean-Paul Clozel. Dari­dorex­ant is one of four de­vel­op­men­tal drugs cur­rent­ly in Idor­sia’s pipeline that has reached the Phase III stage.

Jan Hatzius (Photographer: Christopher Goodney/Bloomberg via Getty Images)

When will it end? Gold­man econ­o­mist gives late-stage vac­cines a good shot at tar­get­ing 'large shares' of the US by mid-2021 — but the down­side is daunt­ing

It took decades for hepatitis B research to deliver a slate of late-stage candidates capable of reining the disease in.

With Covid-19, the same timeline has devoured all of 5 months. And the outcome will influence the lives of billions of people and a multitrillion-dollar world economy.

Count the economists at Goldman Sachs as optimistic that at least one of these leading vaccines will stay on this furiously accelerated pace and get over the regulatory goal line before the end of this year, with a shot at several more near-term OKs. That in turn should lead to the production of billions of doses of vaccines that can create herd immunity in the US by the middle of next year, with Europe following a few months later.

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J&J gets a fresh OK for es­ke­t­a­mine, but is it re­al­ly the game-chang­er for de­pres­sion Trump keeps tweet­ing about?

Backed by an enthusiastic set of tweets from President Trump and a landmark OK for depression, J&J scooped up a new approval from the FDA for Spravato today. But this latest advance will likely bring fresh scrutiny to a drug that’s spurred some serious questions about the data, as well as the price.

First, the approval.

Regulators stamped their OK on the use of Spravato — developed as esketamine, a nasal spray version of the party drug Special K or ketamine — for patients suffering from major depressive disorder with acute suicidal ideation or behavior.

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UP­DAT­ED: No­vavax her­alds the lat­est pos­i­tive snap­shot of ear­ly-stage Covid-19 vac­cine — so why did its stock briefly crater?

High-flying Novavax $NVAX became the latest of the Covid-19 vaccine players to stake out a positive set of biomarker data from its early-stage look at its vaccine in humans.

Their adjuvanted Covid-19 vaccine was “well-tolerated and elicited robust antibody responses numerically superior to that seen in human convalescent sera,” the company noted. According to the biotech:

All subjects developed anti-spike IgG antibodies after a single dose of vaccine, many of them also developing wild-type virus neutralizing antibody responses, and after Dose 2, 100% of participants developed wild-type virus neutralizing antibody responses. Both anti-spike IgG and viral neutralization responses compared favorably to responses from patients with clinically significant COVID‑19 disease. Importantly, the IgG antibody response was highly correlated with neutralization titers, demonstrating that a significant proportion of antibodies were functional.

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Ver­sant de­buts Ridge­line's start­up #4, armed with $30M and al­ter­na­tive TCR cell ther­a­pies for sol­id tu­mors

For all the iterations and advances in TCR therapies for cancer, any experimental treatments involving T cell receptors share one trait: By definition, they only recognize antigens presented as peptides on the major histocompatibility complex (MHC) on cells.

Versant reckons it’s time to expand the arsenal. With $30 million in initial funding, its Ridgeline Discovery Engine in Switzerland has been working on a non-peptidic approach that it says has tumor-agnostic potential, especially in solid tumors. They’ve named it Matterhorn, after a Swiss mountain as they did with the three other companies that have emerged from the Basel-based incubator.

Covid-19 roundup: BAR­DA qui­et­ly pulls plug on IL-6 drugs; BioN­Tech and Fo­s­un be­gin mR­NA tri­al

IL-6 inhibitors showed some early promise in potentially treating Covid-19 patients, but recent trial flops have dashed hopes. Now it appears BARDA has officially pulled the plug.

The HHS office’s website has quietly updated to reflect that it is “no longer supporting product development” for Covid-19 in both Actemra (tocilizumab) and Kevzara (sarilumab), dealing a blow to the Roche and Regeneron/Sanofi drugs. This all but assures that IL-6 drugs repurposed to treat Covid-19 are essentially dead in the water.

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CF Foun­da­tion, Long­wood team on new in­cu­ba­tor for com­pa­nies with cut­ting-edge CF treat­ments

Nine months after launching a $500 million hunt for a cure for cystic fibrosis, the Cystic Fibrosis Foundation said it will use a portion of those funds to do something it has never done before: help launch new companies.

The CF Foundation, whose venture philanthropy efforts helped fund Vertex’s line of powerful CF drugs, is teaming with Longwood Fund to create a CF incubator. The incubator will identify new companies with platforms or technologies that can be applied in the rare genetic condition. The partners can then finance early development in exchange for a commitment from the companies to focus on applications in cystic fibrosis.

Kiersten Stead, John Hamer (DCVC Bio)

Deep tech, round 2: DCVC Bio bags $350M fund to chase the tip of the life sci­ence spear

It took one trip from San Francisco to Vancouver for Kiersten Stead and her DCVC Bio crew to feel confident about throwing their weight — and cash — behind AbCellera.

CEO Carl Hansen’s academic background and the potential of the platform, which combined machine vision and robotics with microfluidics, were promising. But the site visit sealed the Series A deal, where DCVC was the lead and only investor.

No­var­tis says Kym­ri­ah reach­es pri­ma­ry end­point in new PhII, al­though num­bers still to come

The race to develop CAR-T therapies has died down since Novartis’ Kymriah and Gilead’s Yescarta first crossed the finish line, though Tecartus also recently received approval. But the companies continue to expand their drugs’ applications, with Novartis preparing to conclude a new Phase II.

Interim data announced by the Swiss pharma show that Kymriah met its primary endpoint of complete response rate in treating patients with relapsed or refractory follicular lymphoma, the second-most common form of non-Hodgkin lymphoma. Based on preliminary trial findings, Kymriah had received RMAT designation from the FDA in April for r/r follicular lymphoma.

Ab­b­Vie shrugs off $134M cash deals, quit­ting a neu­ro R&D pact with Voy­ager Ther­a­peu­tics on vec­tor­ized an­ti­body treat­ments

It’s the end of the road for Voyager Therapeutics’ collaboration with AbbVie on tau and alpha-synuclein vectorized antibody development.

In two deals spanning the last two years, AbbVie dropped more than $134 million upfront for Voyager’s preclinical R&D of vectorized antibody treatments for diseases like Alzheimer’s and Parkinson’s. But Voyager says AbbVie is walking away now, without offering an explanation for why.