Dario Eklund, Santhera

Months af­ter ax­ing a Duchenne pro­gram and lay­ing off dozens, San­thera claims a win there with a dif­fer­ent pro­gram

Last fall, San­thera Phar­ma­ceu­ti­cals un­cer­e­mo­ni­ous­ly dumped a Duchenne pro­gram af­ter it flunked a Phase III tri­al, forc­ing a wave of lay­offs that trimmed the biotech’s staff from 120 to 40. Now, the Swiss com­pa­ny be­lieves it’s found a path to a come­back with a dif­fer­ent can­di­date in Duchenne.

San­thera re­vealed topline re­sults from a Phase IIb study for its va­morolone pro­gram, say­ing two dif­fer­ent dos­es each hit the pri­ma­ry end­point com­pared with place­bo. Tues­day’s da­ta give the biotech con­fi­dence to po­ten­tial­ly seek ap­proval for both dosage lev­els with the aim of sub­mit­ting an NDA in the first quar­ter of next year.

“This was the last thing that need­ed to fall in­to place for us to be, what I’m col­lo­qui­al­ly call­ing, San­thera 2.0,” CEO Dario Ek­lund told End­points News. “It’s re­al­ly a new start for the com­pa­ny.”

The news sent San­thera shares sky­rock­et­ing in the Swiss stock ex­change more than 60%.

Back in Oc­to­ber, San­thera was forced to halt a Phase III study for its now-de­funct idebenone pro­gram af­ter it failed an in­ter­im analy­sis. The com­pa­ny had been ramp­ing up for a po­ten­tial com­mer­cial launch through­out Eu­rope and had to with­draw its mar­ket­ing au­tho­riza­tion ap­pli­ca­tion from the EMA.

Most of the staffers laid off in the sub­se­quent re­struc­tur­ing were sta­tioned over­seas in more than half a dozen Eu­ro­pean mar­kets, Ek­lund said. The launch had been slat­ed for the first quar­ter of this year, but the re­sult­ing fail­ure forced San­thera to strip “down to the bones.”

Idebenone was de­signed to im­prove lung func­tion in pa­tients by en­er­giz­ing weak­ened mus­cle cells, and had long faced road­blocks in its de­vel­op­ment. The FDA re­ject­ed its orig­i­nal ap­pli­ca­tion for the pro­gram back in 2016 and asked for a con­fir­ma­to­ry tri­al — the tri­al that San­thera ter­mi­nat­ed last fall.

But the va­morolone can­di­date func­tions sim­i­lar to a steroid, which is the stan­dard of care for many Duchenne pa­tients. The Phase IIb study ex­am­ined dosage lev­els of 2 mg/kg per day and 6 mg/kg per day, look­ing at how 121 pa­tients’ time to stand from a supine po­si­tion was short­ened af­ter 24 weeks of treat­ment.

In the high dose, pa­tients re­duced their time to stand from 6 sec­onds to 4.6 sec­onds, while the place­bo group went from 5.4 to 5.5 sec­onds. That equat­ed to a sparkling p-val­ue of p=0.002. San­thera didn’t re­veal the time dif­fer­ence for the low­er dose, but re­port­ed a p-val­ue here of p=0.02. There were “sub­tle dif­fer­ences” in the dose re­spons­es, va­morolone pro­gram lead Shabir Hasham told End­points.

Ide­al­ly, San­thera wants both dos­es to be ap­proved so that pa­tients have the op­tion of down-titrat­ing from the high­er lev­el if they ex­pe­ri­ence side ef­fects. There were no treat­ment-re­lat­ed side ef­fects that reg­is­tered at grade 3 or high­er, but Hasham said about one-third of tri­al par­tic­i­pants in the high­er dose group moved down to the low­er dose.

“Pa­tients can start on a high­er-dose ther­a­py, and those who are com­fort­able can stay while oth­ers come down and don’t lose the ef­fi­ca­cy,” Hasham said. “That’s re­al­ly the unique thing.”

Con­ver­sa­tions with reg­u­la­tors will dic­tate how San­thera ul­ti­mate­ly moves for­ward, Ek­lund said. He hopes that be­cause the can­di­date is an oral so­lu­tion rather than a pill, San­thera’s pitch will prove per­sua­sive — par­tic­u­lar­ly giv­en how typ­i­cal cor­ti­cos­teroid treat­ments used for Duchenne can be down-titrat­ed in a sim­i­lar man­ner.

Last Sep­tem­ber, San­thera picked up glob­al rights to va­morolone from Rever­a­Gen af­ter sign­ing on to the op­tion a few years ago. The com­pa­ny is look­ing to aug­ment the Phase IIb da­ta with re­sults from a pre­vi­ous­ly-re­port­ed Phase IIa study, which Hasham said now shows safe­ty and tol­er­a­bil­i­ty of the pro­gram over 30 months.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Susan Galbraith, AstraZeneca EVP, Oncology R&D

Can­cer pow­er­house As­traZeneca rolls the dice on a $75M cash bet on a buzzy up­start in the on­col­o­gy field

After establishing itself in the front ranks of cancer drug developers and marketers, AstraZeneca is putting its scientific shoulder — and a significant amount of cash — behind the wheel of a brash new upstart in the biotech world.

The pharma giant trumpeted news this morning that it is handing over $75 million upfront to ally itself with Scorpion Therapeutics, one of those biotechs that was newly birthed by some top scientific, venture and executive talent and bequeathed with a fortune by way of a bankroll to advance an only hazily explained drug platform. And they are still very much in the discovery and preclinical phase.

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Lat­est news on Pfiz­er's $3B+ JAK1 win; Pacts over M&A at #JPM22; 2021 by the num­bers; Bio­gen's Aduhelm reck­on­ing; The sto­ry of sotro­vimab; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

For those of you who attended #JPM22 in any shape or form, we hope you had a fruitful time. Regardless of how you spent the past hectic week, may your weekend be just what you need it to be.

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A $3B+ peak sales win? Pfiz­er thinks so, as FDA of­fers a tardy green light to its JAK1 drug abroc­i­tinib

Back in the fall of 2020, newly crowned Pfizer chief Albert Bourla confidently put their JAK1 inhibitor abrocitinib at the top of the list of blockbuster drugs in the late-stage pipeline with a $3 billion-plus peak sales estimate.

Since then it’s been subjected to serious criticism for the safety warnings associated with the class, held back by a cautious FDA and questioned when researchers rolled out a top-line boast that their heavyweight contender had beaten the champ in the field of atopic dermatitis — Dupixent — in a head-to-head study.

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Robert Califf, FDA commissioner nominee (Graeme Sloan/Sipa USA/Sipa via AP Images)

Rob Califf ad­vances as Biden's FDA nom­i­nee, with a close com­mit­tee vote

Rob Califf’s second confirmation process as FDA commissioner is already much more difficult than his near unanimous confirmation under the Obama administration.

The Senate Health Committee on Thursday voted 13-8 in favor of advancing Califf’s nomination to a full Senate vote. Several Democrats voted against Califf, including Sen. Bernie Sanders and Sen. Maggie Hassan. Several other Democrats who aren’t on the committee, like West Virginia’s Joe Manchin and Ed Markey of Massachusetts, also said Thursday that they would not vote for Califf. Markey, Hassan and Manchin all previously expressed reservations about the prospect of Janet Woodcock as an FDA commissioner nominee too.

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Michel Vounatsos, Biogen CEO (World Economic Forum/Ciaran McCrickard)

Bio­gen vows to fight CM­S' draft cov­er­age de­ci­sion for Aduhelm be­fore April fi­nal­iza­tion

Biogen executives made clear in an investor call Thursday they are not preparing to run a new CMS-approved clinical trial for their controversial Alzheimer’s drug anytime soon.

As requested in a draft national coverage decision from CMS earlier this week, Biogen and other anti-amyloid drugs will need to show “a meaningful improvement in health outcomes” for Alzheimer’s patients in a randomized, placebo-controlled trial to get paid for their drugs, rather than just the reduction in amyloid plaques that won Aduhelm its accelerated approval in June.

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CRO own­er pleads guilty to ob­struct­ing FDA in­ves­ti­ga­tion in­to fal­si­fied clin­i­cal tri­al da­ta

The co-owner of a Florida-based clinical research site pleaded guilty to lying to an FDA investigator during a 2017 inspection, revealing that she falsely portrayed part of a GlaxoSmithKline pediatric asthma study as legitimate, when in fact she knew that certain data had been falsified, the Department of Justice said Wednesday.

Three other employees — Yvelice Villaman Bencosme, Lisett Raventos and Maytee Lledo — previously pleaded guilty and were sentenced in connection with falsifying data associated with the trial at the CRO Unlimited Medical Research.

‘Skin­ny la­bels’ on gener­ics can save pa­tients mon­ey, re­search shows, but re­cent court de­ci­sions cloud fu­ture

New research shows how generic drug companies can successfully market a limited number of approved indications for a brand name drug, prior to coming to market for all of the indications. But several recent court decisions have created a layer of uncertainty around these so-called “skinny” labels.

While courts have generally allowed generic manufacturers to use their statutorily permitted skinny-label approvals, last summer, a federal circuit court found that Teva Pharmaceuticals was liable for inducing prescribers and patients to infringe GlaxoSmithKline’s patents through advertising and marketing practices that suggested Teva’s generic, with its skinny label, could be employed for the patented uses.

A patient in Alaska receiving an antibody infusion to prevent Covid hospitalizations in September. All but one of these treatments has been rendered useless by Omicron (Rick Bowmer/AP Images)

How a tiny Swiss lab and two old blood sam­ples cre­at­ed one of the on­ly ef­fec­tive drugs against Omi­cron (and why we have so lit­tle of it)

Exactly a decade before a novel coronavirus broke out in Wuhan, Davide Corti — a newly-minted immunologist with frameless glasses and a quick laugh — walked into a cramped lab on the top floor of an office building two hours outside Zurich. He had only enough money for two technicians and the ceiling was so low in parts that short stature was a job requirement, but Corti believed it’d be enough to test an idea he thought could change medicine.

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