Their lead drug failed both main goals in key study, but Or­p­hazyme plans to pitch sub­group analy­ses to reg­u­la­tors

Or­p­hazyme at­tempt­ed on Wednes­day to en­thuse in­vestors about the re­sults of a Phase II/III study test­ing their lead drug, ari­mo­clo­mol, in pa­tients with a rare ge­net­ic dis­or­der, un­der­scor­ing some pos­i­tive sub­group analy­ses — even though the ex­per­i­men­tal treat­ment missed its pri­ma­ry end­points. The com­pa­ny is now prepar­ing mar­ket­ing fil­ings and plan­ning to en­gage with reg­u­la­tors to get ari­mo­clo­mol on the mar­ket at the ear­li­est.

The com­pa­ny’s shares (CPH: $OR­PHA) shot up about 40% in re­sponse on Wednes­day, but climbed down about 5% on Thurs­day af­ter­noon GMT.

The drug is be­ing eval­u­at­ed for use in Nie­mann-Pick dis­ease Type C (NPC), an in­her­it­ed neu­rode­gen­er­a­tive dis­ease char­ac­ter­ized by the body’s in­abil­i­ty to trans­port cho­les­terol and oth­er lipids in­side of cells that caus­es an ab­nor­mal ac­cu­mu­la­tion with­in var­i­ous tis­sues in­clud­ing the brain. In the 12-month study, 50 pa­tients be­tween the age of 2 and 18 were giv­en ei­ther ari­mo­clo­mol or place­bo on top of stan­dard of care.

The com­pa­ny high­light­ed sub­group analy­ses that sug­gest the drug has a sig­nif­i­cant im­pact on the dis­ease. But that comes af­ter the com­pa­ny ac­knowl­edged months ago that the drug failed the pri­ma­ry end­point.

An­ders Hins­by

“With this high­ly com­pelling da­ta set, we are look­ing for­ward to work­ing with reg­u­la­to­ry au­thor­i­ties to make ari­mo­clo­mol avail­able to pa­tients as fast as pos­si­ble,” Or­p­hazyme chief An­ders Hins­by said in a state­ment.

The tri­al had two pri­ma­ry end­points track­ing dis­ease pro­gres­sion: the 5-do­main NPC Clin­i­cal Sever­i­ty Scale (NPC-CSS), a dis­ease-spe­cif­ic out­come mea­sure, as well as Clin­i­cal Glob­al Im­pres­sion of Im­prove­ment scale (CGI-I), a self-rat­ing tool, at the be­hest of the FDA.

In terms of NPC-CSS, the com­pa­ny said treat­ment with ari­mo­clo­mol ad­junct to rou­tine clin­i­cal care re­sult­ed in a 74% re­duc­tion in dis­ease pro­gres­sion, but the p-val­ue at 0.0506 in­di­cat­ed the ef­fect was not sta­tis­ti­cal­ly sig­nif­i­cant. But re­searchers claimed that two sub­group analy­ses of­fered stronger con­vic­tion of the drug’s po­ten­tial ben­e­fit. When look­ing at pa­tients 4 years or old­er (44/50), treat­ment pro­gres­sion slowed in pa­tients on ari­mo­clo­mol ver­sus place­bo, with a p-val­ue of 0.0219. An­oth­er sub­group analy­sis, re­quest­ed by the EMA, showed that ari­mo­clo­mol had a sig­nif­i­cant im­pact com­pared to a place­bo in pa­tients who got miglu­s­tat — orig­i­nal­ly sold by Acte­lion un­der the brand name Za­vesca — as part of stan­dard care, with a p-val­ue of 0.0071.

On the CGI-I end­point, an in­flat­ed place­bo re­sponse de­terred the drug from demon­strat­ing an im­pact on the main goal, the com­pa­ny said, adding that when con­sid­er­ing pa­tients who se­vere­ly pro­gressed dur­ing the tri­al, on­ly 10.7% of ari­mo­clo­mol-treat­ed pa­tients got “much worse” or “very much worse” com­pared to 26.7% in the place­bo con­trol group.

Oth­er sub­group analy­ses al­so sug­gest­ed a lack of sta­tis­ti­cal sig­nif­i­cant im­prove­ment with the drug, al­though some ex­plorato­ry bio­mark­er da­ta were fa­vor­able to ari­mo­clo­mol.

Safe­ty da­ta were al­so pos­i­tive, with se­ri­ous side-ef­fects oc­cur­ring less fre­quent­ly in the ari­mo­clo­mol group (14.7%) com­pared to place­bo con­trol (37.5%).

The ball is now in the reg­u­la­to­ry court, but con­sid­er­ing NPC is a rare dis­ease af­fect­ing an es­ti­mat­ed in 1/120 000 live births, it could go ei­ther way.

Susan Galbraith, AstraZeneca EVP, oncology R&D, at EUBIO22 (Rachel Kiki for Endpoints News)

Up­dat­ed: As­traZeneca jumps deep­er in­to cell ther­a­py 2.0 space with $320M biotech M&A

Right from the start, the execs at Neogene had some lofty goals in mind when they decided to try their hand at a cell therapy that could tackle solid tumors.

Its founders have helped hone a new approach that would pack in multiple neoantigen targets to create a personalized TCR treatment that would not just make the leap from blood to solid tumors, but do it with durability. And they managed to make their way rapidly to the clinic, unveiling their first Phase I program for advanced tumors just last May.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Ei­sai’s ex­pand­ed Alzheimer’s da­ta leave open ques­tions about safe­ty and clin­i­cal ben­e­fit

Researchers still have key questions about Eisai’s investigational Alzheimer’s drug lecanemab following the publication of more Phase III data in the New England Journal of Medicine Tuesday night.

In the paper, which was released in conjunction with presentations at an Alzheimer’s conference, trial investigators write that a definition of clinical meaningfulness “has not been established.” And the relative lack of new information, following topline data unveiled in September, left experts asking for more — setting up a potential showdown to precisely define how big a difference the drug makes in patients’ lives.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

iECURE CEO Joe Truitt and founder Jim Wilson

Jim Wil­son biotech iECURE gets fresh $65M to push pe­di­atric liv­er dis­ease gene ther­a­py in­to the clin­ic

Jim Wilson-founded biotech iECURE has wrapped a $65M Series A extension round to get its lead candidate — a gene replacement therapy for a rare inherited liver disease known as ornithine transcarbamylase deficiency, or OTC — into the clinic.

This round was co-led by Novo Holdings and LYFE Capital, followed by initial investors Versant and OrbiMed as well. In September 2021, iECURE raised a $50 million Series A led by the latter two. The new cash infusion will get iECURE through an initial in-human trial, which CEO Joe Truitt told Endpoints News iECURE hopes to read out in 2024.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 153,900+ biopharma pros reading Endpoints daily — and it's free.

Illustration: Assistant Editor Kathy Wong for Endpoints News

Twit­ter dis­ar­ray con­tin­ues as phar­ma ad­ver­tis­ers ex­tend paus­es and look around for op­tions, but keep tweet­ing

Pharma advertisers on Twitter are done — at least for now. Ad spending among the previous top spenders flattened even further last week, according to the latest data from ad tracker Pathmatics, amid ongoing turmoil after billionaire boss Elon Musk’s takeover now one month ago.

Among 18 top advertisers tracked for Endpoints News, only two are spending: GSK and Bayer. GSK spending for the full week through Sunday was minimal at just under $1,900. Meanwhile, German drugmaker Bayer remains the industry outlier upping its spending to $499,000 last week from $480,000 the previous week. Bayer’s spending also marks a big increase from a month ago and before the Musk takeover, when it spent $16,000 per week.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Vi­a­tris with­draws ac­cel­er­at­ed ap­proval for top­i­cal an­timi­cro­bial 24 years lat­er

After 24 years without confirming clinical benefit, the FDA announced Tuesday morning that Viatris (formed via Mylan and Pfizer’s Upjohn) has decided to withdraw a topical antimicrobial agent, Sulfamylon (mafenide acetate), after the company said conducting a confirmatory study was not feasible.

Sulfamylon first won FDA’s accelerated nod in 1998 as a topical burn treatment, with the FDA noting that last December, Mylan told the agency that it wasn’t running the trial.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 153,900+ biopharma pros reading Endpoints daily — and it's free.

Catal­ent to cut about 200 jobs in Mary­land and Texas

Contract manufacturing company Catalent is cutting about 200 jobs in Maryland and Texas, according to WARN notices, trimming back some of its pandemic-era expansion.

The company will cut 77 jobs by Jan. 15 of next year at a cell therapy facility in Webster, TX, just outside of Houston. In Maryland, the company is reducing staff at two locations, with 82 jobs being eliminated at Catalent’s facility in Gaithersburg, and 53 in Rockville. The layoffs go into effect at those locations on Jan. 14.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 153,900+ biopharma pros reading Endpoints daily — and it's free.

John Carroll with David Chang, Allogene CEO (Credit: Jeff Rumans Photography)

Al­lo­gene takes the stage in New York to go deep on its off-the-shelf cell ther­a­pies — de­clar­ing a first for sol­id tu­mors

NEW YORK — In most cases, a biotech like Allogene would wait until the next big science conference to offer its latest series of snapshots of its data. But most biotechs aren’t like Allogene, where the veteran leaders from Kite garnered a substantial number of kudos over the years for their in-depth reviews of the company’s progress.

So on Tuesday, the leaders at Allogene converged on Manhattan once again to give a detailed breakdown of their latest steps forward, looking to stay out front in the busy off-the-shelf cell therapy arena, keep a clean bill of health on the safety front and prove that they can not only match the autologous pioneers they helped create but make the all-important leap into solid tumors. It’s another step forward in a journey that has a long way to go before even the first big regulatory finish lines appear on the track. But for CEO David Chang, who spent some time with me running through the data ahead of the Tuesday session, it all amounts to forward momentum toward the desired goal.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

UK reg­u­la­tor warns of se­vere eye re­ac­tions fol­low­ing use of Sanofi and Re­gen­eron's Dupix­ent

The UK’s Medicines and Healthcare Regulatory Agency (MHRA) on Tuesday warned of some new and serious eye-related side effects following the use of Sanofi and Regeneron’s atopic dermatitis and asthma treatment Dupixent (dupilumab).

While Dupixent is already associated with cases of conjunctivitis and allergic conjunctivitis, dry eye and with infrequent cases of keratitis and ulcerative keratitis, the MHRA is calling on health professionals to be on the lookout for any of these eye-related side effects as “it is not currently possible to predict who may experience the rarer and most severe ocular adverse reactions, such as ulcerative keratitis.”

Sana, Codex­is lay off staff, reshuf­fle pipeline in bid to fo­cus cell ther­a­py, en­zyme en­gi­neer­ing work

As its market cap shrinks to a fraction of its heyday, flashy cell therapy startup Sana Biotechnology is laying off 15% of its staffers in a move to rejig the pipeline and restructure the company.

Sana is among a growing group of biotechs that, feeling the weight of a broader market downturn and seeing their shares tumble steadily, are tightening the purse strings and adjusting their focus. Also on Tuesday, Codexis, an enzyme engineering company based in California and now helmed by former Sierra Oncology CEO Stephen Dilly, announced it will reduce the workforce by 18%.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 153,900+ biopharma pros reading Endpoints daily — and it's free.