Stan­ley and Rosanne Crooke stay fo­cused on an­ti-sense, steal­ing back pa­tients from dis­ease with N-of-1 tech

A lit­tle over a year af­ter a Boston Chil­dren’s Hos­pi­tal neu­rol­o­gist used an­ti-sense tech­nol­o­gy to cre­ate what may be the world’s first ful­ly be­spoke ther­a­py, two of the old­est and biggest names in an­ti-sense have launched a char­i­ty to make those treat­ments pos­si­ble to far more pa­tients – and free of charge.

Stan­ley Crooke

The hus­band-and-wife team of long­time Io­n­is CEO Stan­ley Crooke and long­time Io­n­is re­searcher Rosanne Crooke are launch­ing the n-Lorem foun­da­tion. The cou­ple will per­son­al­ly con­tribute $1.5 mil­lion to the project, with Io­n­is adding an­oth­er $1.5 mil­lion and Bio­gen $1 mil­lion. Stan­ley Crooke stepped down from Io­n­is’ helm last year.

Found­ed by Crooke in 1989, Io­n­is was the first com­pa­ny to launch a clin­i­cal tri­al for an­ti-sense tech­nol­o­gy, sin­gle strands of RNA that can be used to reg­u­late gene ex­pres­sion. The tech­nol­o­gy has since be­come a ver­i­fied ap­proach, lead­ing to drugs such as Spin­raza and Waylivra.

The ad­vance­ments crys­tal­lized in 2018, when, in un­der 10 months, Tim­o­thy Yu used an­ti-sense tech­nol­o­gy to cus­tomize a treat­ment for a 6-year-old girl who came in­to Boston’s Chil­dren’s Hos­pi­tal with a nev­er-be­fore-seen ge­net­ic mu­ta­tion. The news sparked hope and prompt­ed pleas for their own ther­a­pies from fam­i­lies af­fect­ed by rare mu­ta­tions.

Rosanne Crooke

The Crookes launched the new foun­da­tion to make these “N-of-1” ther­a­pies pos­si­ble for more of those fam­i­lies. Stan­ley Crooke told Chem­i­cal & En­gi­neer­ing News that he sees this n-Lo­ram as a mid­dle man who can co­or­di­nate be­tween all the parts re­quired to scale be­spoke treat­ments: Pa­tients, a clin­i­cian who can man­age a one-pa­tient tri­al, and an in­sti­tu­tion who can sub­mit an IND-en­abling ap­pli­ca­tion, among oth­er things.

“I con­ceived of n-Lorem as sort of the mid­dle man—the bro­ker of the ge­net­ics, the pa­tients, the needs, and one so­lu­tion to bring ther­a­peu­tic op­tions for these pa­tients who have ul­tra, ul­tra-rare mu­ta­tions,” Crooke told C&EN.

The foun­da­tion will con­vene an “ac­cess to treat­ment” pan­el of re­searchers, pa­tients and Bio­gen and Io­n­is ex­ec­u­tives. They will re­view US-based pa­tients who come through the Un­di­ag­nosed Dis­ease Net­work, a group of NIH-fund­ed sites with ex­per­tise in ul­tra-rare dis­eases.

There will be sig­nif­i­cant road­blocks, though. In ad­di­tion to the sci­en­tif­ic hur­dles of de­vel­op­ing in­di­vid­u­al­ized ther­a­pies, it’s still un­clear how the FDA will re­spond. When the New Eng­land Jour­nal of Med­i­cine pub­lished Yu’s work in Oc­to­ber, they ac­com­pa­nied it with an op-ed from the FDA’s Janet Wood­cock and Pe­ter Marks. The pair de­tailed 9 dif­fer­ent ques­tions reg­u­la­tors will face go­ing for­ward and pro­vid­ed few an­swers.

“In these ‘N-of-one’ sit­u­a­tions, what type of ev­i­dence is need­ed be­fore ex­pos­ing a hu­man to a new drug?” they wrote. “Even in rapid­ly pro­gress­ing, fa­tal ill­ness­es, pre­cip­i­tat­ing se­vere com­pli­ca­tions or death is not ac­cept­able, so what is the min­i­mum as­sur­ance of safe­ty that is need­ed? How per­sua­sive should the mech­a­nis­tic or func­tion­al da­ta be? How should the dose and reg­i­men be se­lect­ed? How much char­ac­ter­i­za­tion of the prod­uct should be un­der­tak­en? How should the ur­gency of the pa­tient’s sit­u­a­tion or the num­ber of peo­ple who could ul­ti­mate­ly be treat­ed af­fect the de­ci­sion-mak­ing process?”

So­cial im­age cred­it: Oligonu­cleotide Ther­a­peu­tics So­ci­ety

2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

Aymeric Le Chatelier, Ipsen

A $1B-plus drug stum­bles in­to an­oth­er big PhI­II set­back -- this time flunk­ing fu­til­i­ty test -- as FDA hold re­mains in ef­fect for Ipsen

David Meek

At the time Ipsen stepped up last year with more than a billion dollars in cash to buy Clementia and a late-stage program for a rare bone disease that afflicts children, then CEO David Meek was confident that he had put the French biotech on a short path to a mid-2020 launch.

Instead of prepping a launch, though, the company was hit with a hold on the FDA’s concerns that a therapy designed to prevent overgrowth of bone for cases of fibrodysplasia ossificans progressiva might actually stunt children’s growth. So they ordered a halt to any treatments for kids 14 and under. Meek left soon after to run a startup in Boston. And today the Paris-based biotech is grappling with the independent monitoring committee’s decision that their Phase III had failed a futility test.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 70,500+ biopharma pros reading Endpoints daily — and it's free.

Roche's check­point play­er Tecen­triq flops in an­oth­er blad­der can­cer sub­set

Just weeks after Merck’s star checkpoint inhibitor Keytruda secured FDA approval for a subset of bladder cancer patients, Swiss competitor Roche’s Tecentriq has failed in a pivotal bladder cancer study.

The 809-patient trial — IMvigor010 — tested the PD-L1 drug in patients with muscle-invasive urothelial cancer (MIUC) who had undergone surgery, and were at high risk for recurrence.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 70,500+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: Eli Lil­ly’s $1.6B can­cer drug failed to spark even the slight­est pos­i­tive gain for pa­tients in its 1st PhI­II

Eli Lilly had high hopes for its pegylated IL-10 drug pegilodecakin when it bought Armo last year for $1.6 billion in cash. But after reporting a few months ago that it had failed a Phase III in pancreatic cancer, without the data, its likely value has plunged. And now we’re getting some exact data that underscore just how little positive effect it had.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 70,500+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 70,500+ biopharma pros reading Endpoints daily — and it's free.

Gilead dusts off a failed Ebo­la drug as coro­n­avirus spreads; Ex­elix­is boasts pos­i­tive Ph I/II da­ta

→ Less than a year ago Gilead’s antiviral remdesivir failed to make the cut as investigators considered a raft of potential drugs that could be used against an Ebola outbreak. But it may gain a new mission with the outbreak of the coronavirus in China, which is popping up now around the world.

Gilead put out a statement saying that they’re now in discussions with health officials in the US and China about testing their NUC against the virus. It’s the latest in a growing lineup of biopharma companies that are marshaling R&D forces to see if they can come up with a vaccine or therapy to blunt the spread of the virus, which has now sickened hundreds, killed at least 17 people and led the Chinese government to start quarantining cities.

Alex Karnal (Deerfield)

Deer­field vaults to the top of cell and gene ther­a­py CD­MO game with $1.1B fa­cil­i­ty at Philadel­phi­a's newest bio­phar­ma hub

Back at the beginning of 2015, Deerfield Management co-led a $10 million Series C for a private gene therapy startup, reshaping the company and bringing in new leaders to pave way for an IPO just a year later.

Fast forward four more years and the startup, AveXis, is now a subsidiary of Novartis marketing the second-ever gene therapy to be approved in the US.

For its part, Deerfield has also grown more comfortable and ambitious about the nascent field. And the investment firm is now putting down its biggest bet yet: a $1.1 billion contract development and manufacturing facility to produce everything one needs for cell and gene therapy — faster and better than how it’s currently done.

Tri­fec­ta of sick­le cell dis­ease ther­a­pies ex­tend life ex­pectan­cy, but are not cost-ef­fec­tive — ICER

Different therapeutic traits brandished by the three approved therapies for sickle cell disease all extend life expectancy, but their impact on quality of life is uncertain and their long-term cost-effectiveness is not up to scratch according to the thresholds considered reasonable by ICER, the non-profit concluded in a draft guidance report on Thursday.

Sickle cell disease (SCD), which encompasses a group of inherited red blood cell disorders that typically afflict those of African ancestry, impacts hemoglobin — and is characterized by episodes of searing pain as well as organ damage.