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.

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In­no­v­a­tive MedTech De­mands Spe­cial­ist Clin­i­cal Tri­al Reg­u­la­to­ry Af­fairs and De­sign

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Mathai Mammen (Rob Tannenbaum, Endpoints News at BIO 2018)

Math­ai Mam­men makes an abrupt ex­it as head of the big R&D group at J&J

In an after-the-bell shocker, J&J announced Monday evening that Mathai Mammen has abruptly exited J&J as head of its top-10 R&D group.

Recruited from Merck five years ago, where the soft-spoken Mammen was being groomed as the successor to Roger Perlmutter, he had been one of the top-paid R&D chiefs in biopharma. His group spent $12 billion last year on drug development, putting it in the top 5 in the industry.

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Robert Califf, FDA commissioner (Tom Williams/CQ Roll Call via AP Images)

Hop­ing to ex­pand mon­key­pox vac­cine sup­ply, US paves the way for new route of ad­min­is­tra­tion

After making it clear that the US’ current monkeypox vaccine supply is insufficient, the FDA on Tuesday authorized a new route of administration that should increase the number of available doses by five-fold.

Regulators cleared Bavarian Nordic’s Jynneos vaccine for intradermal injection in adults older than 18. Unlike subcutaneous injection — the current method by which vaccine is delivered under the skin — an intradermal jab goes directly into the skin. It’s believed that this method requires less vaccine, since the dermis is rich in dendritic cells which specialize in taking up foreign antigens and presenting them to the immune system, according to Daniel Kuritzkes, chief of infectious diseases at Brigham and Women’s Hospital in Boston.

Samantha Du, Zai Lab CEO

Any­one still look­ing for a CD47? Zai Lab shelves PhI pro­gram af­ter re­view­ing 'com­pet­i­tive land­scape'

Over the past few years, the promise of blocking CD47 — a “don’t eat me” signal co-opted by cancer cells — has sent drugmakers big and small into a frenzy. But one biotech is now bowing out.

Zai Lab is deprioritizing ZL-1201, its CD47 inhibitor, scrapping plans for a Phase II trial. It will now “pursue out-licensing opportunities,” the company said in its Q2 update. The decision was based on a review of the competitive landscape, it added, without going into further details.

Illustration: Kim Ryu for Endpoints News

Why non-opi­oid pain drugs keep fail­ing — and what's next for the field

In 1938, Rita Levi-Montalcini was forced to move her lab into her bedroom in Turin, as Mussolini’s facist government expelled Jewish people from studying or working in schools in Italy. Levi-Montalcini, then just a few years out of medical school and using sewing needles as scalpels in her makeshift lab, would soon discover nerve growth factor, or NGF, in chicken embryos.

Her discoveries formed the basis of our understanding of the peripheral nervous system and how cells talk to each other, and Levi-Montalcini went on to win the Nobel Prize in 1986. Much later, NGF was hailed as a promising target for new pain therapies, with some analysts quoting an $11 billion market. However, the latest anti-NGF candidate, Pfizer and Eli Lilly’s tanezumab, was rejected by the FDA last year because of a side effect that dissolved bone in some of its patients.

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Ted Love, Global Blood Therapeutics CEO

Up­dat­ed: Pfiz­er scoops up Glob­al Blood Ther­a­peu­tics and its sick­le cell ther­a­pies for $5.4B

Pfizer is dropping $5.4 billion to acquire Global Blood Therapeutics.

Just ahead of the weekend, word got out that Pfizer was close to clinching a $5 billion buyout — albeit with other potential buyers still at the table. The pharma giant, flush with cash from Covid-19 vaccine sales, apparently got out on top.

The deal immediately swells Pfizer’s previously tiny sickle cell disease portfolio from just a Phase I program to one with an approved drug, Oxbryta, plus a whole pipeline that, if all approved, the company believes could make for a $3 billion franchise at peak.

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Steve Paul, Karuna Therapeutics CEO (Third Rock)

Karuna's schiz­o­phre­nia drug pass­es a close­ly-watched PhI­II test, will head to FDA in mid-2023

An investigational pill that combines a former Eli Lilly CNS compound with an overactive bladder drug was better than placebo at reducing a scale of symptoms experienced by patients with schizophrenia in a Phase III trial.

Karuna Therapeutics’ drug passed the primary goal in EMERGENT-2, the Boston biotech said early Monday morning, alongside quarterly earnings. The study is the first of Karuna’s four Phase III clinical trials to read out in schizophrenia and will provide the backbone to the biotech’s first drug approval application, slated for mid-2023.

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HHS Secretary Xavier Becerra (Patrick Semansky/AP Images)

US weighs new route of ad­min­is­tra­tion for mon­key­pox vac­cine as cas­es climb — re­port

Less than a week after HHS Secretary Xavier Becerra declared monkeypox a national health emergency, reports have emerged that the US plans to extend its vaccine supply by opting for a different route of administration.

Officials are expected to call for intradermal injection of Bavarian Nordic’s Jynneos vaccine — the only shot approved specifically for monkeypox in the US — as opposed to subcutaneous injection, unnamed sources told both the New York Times and Washington Post on Tuesday.

'Messy at best': Is the US re­peat­ing the same Covid mis­steps with mon­key­pox mes­sag­ing?

When Kyle Planck first suspected he might have monkeypox in late June, he went to the CDC website and found six photos of different types of lesions. And that was about it for general public information.

Planck, who is a sixth-year PhD pharmacology researcher at Weill Cornell, kept looking though and found a separate part of the CDC website meant for healthcare professionals. There he found a medical slide deck with more pictures, professional journal articles and more details about symptoms and diagnosis.

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