An­oth­er failed tri­al for Or­p­hazyme's 'pipeline-in-a-pro­duc­t' leaves shad­ow on drug's fu­ture

The tu­mul­tuous ride for Or­p­hazyme con­tin­ued on Fri­day as the com­pa­ny an­nounced that a piv­otal tri­al for its lead drug ari­mo­clo­mol failed yet again, this time in the treat­ment of ALS, seed­ing doubt in a drug that had re­cent­ly been cleared by the FDA for pri­or­i­ty re­view. The lat­est fail­ure casts a dark­er shad­ow on the up­com­ing de­ci­sion de­spite Or­p­hazyme’s up­beat out­look.

In a state­ment, the Dan­ish biotech an­nounced that the drug did not meet its pri­ma­ry or sec­ondary end­points eval­u­at­ing func­tion and sur­vival. But the com­pa­ny has not an­nounced any da­ta sur­round­ing the fail­ure, in­stead say­ing that it will pub­lish the com­plete re­sults lat­er this year.

In­vestors re­act­ed ac­cord­ing­ly to the news, as the $ORPH stock dropped 24.16% pre­mar­ket to $6.41.

Or­p­hazyme is a 1-drug com­pa­ny and has ex­pec­ta­tions that ari­mo­clo­mol — dubbed its “pipeline-in-a-prod­uct” — has the abil­i­ty to treat sev­er­al dif­fer­ent dis­eases. The com­pa­ny pur­chased the drug from CytRx in 2011 for $150,000 up­front, and the po­ten­tial to make $120 mil­lion. But with that chal­lenge has come re­peat­ed frus­tra­tion as this is not the first time that the drug has flopped.

In March, the com­pa­ny an­nounced that ari­mo­clo­mol failed to hit its end­points in Phase II/III tri­als for pa­tients with in­clu­sion body myosi­tis, a de­bil­i­tat­ing mus­cle-wast­ing dis­ease. The com­pa­ny al­so in­tends to ad­vance ari­mo­clo­mol in­to clin­i­cal de­vel­op­ment in Gauch­er dis­ease, the in­her­it­ed dis­or­der that caus­es sug­ar-con­tain­ing fats to ac­cu­mu­late in the lyso­somes of cells and af­fect the brain, bone mar­row, spleen and liv­er. That pro­gram is cur­rent­ly in Phase II.

Thomas Blaet­tler

The drug just bare­ly missed both pri­ma­ry end­points in its Phase III Nie­mann-Pick dis­ease type C study rough­ly 2.5 years ago. But the FDA ac­cept­ed its ap­pli­ca­tion in Sep­tem­ber 2020 for the rare neu­rode­gen­er­a­tive con­di­tion and gave it pri­or­i­ty re­view, re­in­forc­ing Or­p­hazyme’s nar­ra­tive that the FDA viewed the ap­pli­ca­tion fa­vor­ably.  There is no ap­proved med­i­cine for NPC, a rare dis­ease that is es­ti­mat­ed to im­pact 1 in 100,000 lives.

“We are dis­heart­ened by these re­sults, as we had hoped ari­mo­clo­mol might rep­re­sent a vi­able new ap­proach against the for­mi­da­ble chal­lenge of this dev­as­tat­ing dis­ease,” CMO Thomas Blaet­tler said. “With over 18 months of eval­u­a­tion, this tri­al rep­re­sents one of the longest run­ning clin­i­cal stud­ies in this cat­e­go­ry. While un­suc­cess­ful, the da­ta gen­er­at­ed will con­tribute mean­ing­ful­ly to the sci­en­tif­ic di­a­logue on this chal­leng­ing dis­ease.”

The PDU­FA date for Nie­mann-Pick is June 17.

The com­pa­ny is in the midst of a tough stretch. In De­cem­ber 2020, then-CEO Kim Strat­ton re­signed abrupt­ly, and Or­p­hazyme of­fered no ex­pla­na­tion for the move oth­er than that the choice was Strat­ton’s de­ci­sion “fol­low­ing a di­a­logue ini­ti­at­ed by the board of di­rec­tors.”

The drug just nar­row­ly missed its first pri­ma­ry end­point on its 50-per­son Phase II/III NPC study back in Jan­u­ary 2019. Sci­en­tists saw both a 74% re­duc­tion in dis­ease sever­i­ty and a p-val­ue of 0.0506. Two pre-spec­i­fied sub­group analy­ses reached sig­nif­i­cance, with dis­ease pro­gres­sion slow­ing in pa­tients over the age of 4 and in pa­tients who had been tak­ing an Acte­lion drug some­times pre­scribed for the dis­ease. But for this round of tri­als in ALS, the com­pa­ny did not re­lease any da­ta, leav­ing the pub­lic in the dark as to how it per­formed in the tri­al.

Topline da­ta will be pre­sent­ed at the vir­tu­al Eu­ro­pean Net­work to Cure ALS meet­ing from May 12-14, the com­pa­ny said in a state­ment, while com­plete da­ta will be pub­lished lat­er in the year.

The ran­dom­ized, place­bo-con­trolled tri­al for ALS fea­tured 245 at 29 sites across 12 coun­tries in North Amer­i­ca and Eu­rope, the com­pa­ny said in its re­lease. Pa­tients ei­ther re­ceived 3 dai­ly 248mg dos­es of ari­mo­clo­mol or the place­bo for up to 76 weeks.

The pri­ma­ry end­point was to de­ter­mine the ef­fi­ca­cy through the com­bined as­sess­ment of func­tion and sur­vival, and the sec­ondary end­points in­clud­ed sur­vival, ALS Func­tion­al Rat­ing Scale-Re­vised and slow vi­tal ca­pac­i­ty.

Christophe Bour­don, Or­p­hazyme CEO

In­side Track: Be­hind the Scenes of a Ma­jor Biotech SPAC

Dr. David Hung and Michelle Doig are no strangers to the SPAC phenomenon. As Founder and CEO of Nuvation Bio, a biotech company tackling some of the greatest unmet needs in oncology, Dr. Hung recently took the company public in one of this year’s biggest SPAC related deals. And as Partner at Omega Funds, Doig not only led and syndicated Nuvation Bio’s Series A, but is now also President of the newly formed, Omega-sponsored, Omega Alpha SPAC (Nasdaq: OMEG; oversubscribed $138m IPO priced January 6, 2021).

In a first, Re­gen­eron's an­ti­body cock­tail re­duces deaths for a sub­group of hos­pi­tal­ized Covid-19 pa­tients

Scientists have come up with the first evidence that Regeneron’s antibody cocktail, which has so far only been authorized for the outpatient setting, may reduce deaths of hospitalized Covid-19 patients — albeit only a subset.

The combination of casirivimab and imdevimab is the subject of the latest data cut from RECOVERY, the large-scale UK-based trial testing a variety of potential treatments. In total, 9,785 patients hospitalized with Covid-19 were enrolled in this arm of the study and were randomly assigned to receive either usual care plus the intravenous combo or usual care alone.

Janet Woodcock, acting FDA commissioner (Al Drago/Bloomberg via Getty Images)

New Alzheimer's drug ap­proval fall­out: Pub­lic Cit­i­zen seeks re­moval of FDA's Wood­cock, Cavaz­zoni and Dunn

As Capitol Hill begins to wake up to the financial and scientific mess behind the FDA’s approval of Biogen’s new controversial Alzheimer’s drug Aduhelm, nonprofit watchdog Public Citizen is now calling for the top three FDA officials who are responsible to be removed from their positions.

In a letter to HHS Secretary Xavier Becerra on Wednesday, the group highlighted the “litany of flaws” in the FDA’s approval of the new drug, including the “unprecedented, inappropriately close” collaboration between the FDA and Biogen in the analysis of key trial data, basing approval on an unvalidated surrogate endpoint, not following the advice of its expert advisory committee (3 members of which have since resigned), and the wide label that the agency granted.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,500+ biopharma pros reading Endpoints daily — and it's free.

Barry Greene, Sage CEO

UP­DAT­ED: Sage's sec­ond chance at de­pres­sion hits the PhI­II pri­ma­ry, but ques­tions re­main over dura­bil­i­ty, side ef­fects

Looking to make a comeback after a big Phase III flop, Sage Therapeutics revealed data they believe could change the entire depression treatment landscape, given the vast array of failures in the field. But some results are spooking investors, sending Sage $SAGE shares down early Tuesday.

First, the primary: Sage and Biogen reported Phase III data for once-daily zuranolone Tuesday morning, saying the experimental drug hit its primary endpoint by spurring a statistically significant change from baseline in the 17-item Hamilton Rating Scale for Depression total score. After 15 days, patients in the drug arm saw an average change of -14.1 points, compared to -12.3 on placebo.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,500+ biopharma pros reading Endpoints daily — and it's free.

Bio­gen sig­nals a big PhI­II fail­ure as the lead gene ther­a­py in their $800M Night­star buy­out goes down in flames

That $800 million buyout of Nightstar has turned into a bust for Biogen as the lead therapy in the deal failed a pivotal study, signaling a severe setback for the biotech’s ambitions in gene therapies.

The big biotech put out the word after the market closed on Monday that the gene therapy they picked up in the deal for a degenerative blindness called choroideremia failed the Phase III study, just a month after their #2 drug in the deal also flopped in a mid-stage study.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,500+ biopharma pros reading Endpoints daily — and it's free.

Aus­tralian spin­out eyes the clin­ic with a pro­phy­lac­tic nasal spray for Covid-19

Whether patients are immunocompromised or just don’t like needles, one fledgling Australian biotech says it has an alternative to Covid-19 vaccines that doesn’t involve a jab in the arm — and on Tuesday, it pulled in a fresh round of funding to take it into the clinic.

ENA Respiratory, which spun out of ENA Therapeutics last year, has pulled in nearly $24.7 million (AU $30 million) to advance its nasal spray for respiratory viral infections, the company said Tuesday.

Someit Sidhu, JATT

An­oth­er life sci­ences SPAC has popped up from a small biotech CEO with the help of Take­da, No­var­tis vet­er­ans

Editor’s note: Interested in following biopharma’s fast-paced IPO market? You can bookmark our IPO Tracker here.

The SPAC train has slowed down since the extraordinarily high levels from late 2020 into early this year, but Tuesday saw the filing of a new blank-check company targeting the life sciences industry.

Jatt Acquisition submitted its SEC paperwork Tuesday, penciling in an estimated raise of $120 million as it sets its sights on a reverse merger partner. The SPAC is run by Someit Sidhu, a co-founder of Pathios Therapeutics, as well as CEO of Akaza Bioscience and Izana Bioscience. Sidhu will control about 97% of the blank-check company’s shares, per the S-1.

CEO Harith Rajagopalan (Fractyl)

Af­ter a decade in the type 2 di­a­betes game, Fractyl Lab­o­ra­to­ries recharges with a fresh $100M and a new name

Harith Rajagopalan compared the way type 2 diabetes is managed to sticking your fingers in a dam that’s leaking from a number of places.

You can take drugs to lower your blood sugar, cholesterol, or blood pressure, but you’re not addressing what he says is the core issue — the metabolic abnormality that causes the disease.

“We’re so busy plugging the holes in the dam, we don’t have time to see that the whole infrastructure is at risk,” he said. “That infrastructure is a full-body systemic metabolic abnormality called metabolic syndrome, that we’re ignoring while we’re so busy trying to treat all of the individual symptoms of the condition.”

Michel Sade­lain puts his name and new cell en­gi­neer­ing tech be­hind 'ag­nos­tic' CAR-T start­up chas­ing epi­ge­net­ic anti­gens

It felt natural for Alain Maiore and Sebastian Amigorena to bring in Michel Sadelain as a co-founder of Mnemo Therapeutics. A CAR-T pioneer, Sadelain had been involved as an advisor since the early days — enthusiastic about Amigorena’s work in a genetic knockout that could enhance T cell memory and a new class of potential targets he’s discovered — and could introduce some well-known technologies to the toolbox. So they got the initial cash from Sofinnova Partners to plant roots in Paris and New York in early 2019; within a few months, they began to see more clearly just what the antigen discovery platform might unlock.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,500+ biopharma pros reading Endpoints daily — and it's free.