Henry Klassen (UC Irvine via YouTube)

Can prog­en­i­tor cells go fur­ther than gene ther­a­py in reti­nal dis­or­ders? A biotech's an­swer shines in PhI­Ib

By the time the FDA ap­proved Lux­tur­na — the pi­o­neer­ing gene ther­a­py for an in­her­it­ed reti­nal dis­ease — Hen­ry Klassen had been re­search­ing and treat­ing the group of dis­eases known as re­tini­tis pig­men­tosa for more than 20 years.

Spark Ther­a­peu­tics’ suc­cess there had not just in­spired a $4.3 bil­lion takeover by Roche, it had al­so em­bold­ened oth­er biotechs pur­su­ing a ther­a­py that would de­liv­er one of the genes tied to dif­fer­ent vari­a­tions of the dis­or­der. Night­star Ther­a­peu­tics sub­se­quent­ly scored its own buy­out with Bio­gen, and MeiraGTx re­cent­ly post­ed ear­ly but “ex­cit­ing da­ta” on its J&J-part­nered pro­gram.

But Klassen went a dif­fer­ent way.

Catch­ing on the stem cell craze right at the turn of the mil­len­ni­um, he took in­spi­ra­tion from sci­en­tists who trans­plant­ed neur­al prog­en­i­tor cells in­to the reti­na and de­vel­oped a method to grow reti­nal prog­en­i­tor cells in­stead as a ther­a­py. Start­ing out as the di­rec­tor of stem cell re­search at the Chil­dren’s Hos­pi­tal of Or­ange Coun­ty, he con­tin­ued the work at the Uni­ver­si­ty of Cal­i­for­nia, Irvine, even­tu­al­ly spin­ning out a biotech dubbed jCyte in 2012.

Paul Bres­ge

Over the week­end jCyte re­port­ed pos­i­tive Phase IIb re­sults from what they call one of the largest stud­ies ever con­duct­ed in RP, sug­gest­ing that pa­tients on the treat­ment saw im­proved func­tion­al vi­sion com­pared to the place­bo group.

“The cred­it to the gene ther­a­pies is that they’re ac­tive­ly try­ing to fix the gene un­der­ly­ing the prob­lem. That’s very com­mend­able, and we’re not do­ing that,” Klassen told End­points News. “But our treat­ment as it stands should have im­pact across a va­ri­ety of dif­fer­ent geno­types.”

The study en­rolled a to­tal of 84 pa­tients, of whom 74 were in­clud­ed for the fi­nal analy­sis. For each pa­tient on the pri­ma­ry end­point of best cor­rect­ed vi­su­al acu­ity (mea­sured with glass­es on), the mean change from base­line to month 12 for the sham, low dose and high dose arms were +2.81, +2.96, and +7.43 let­ters, re­spec­tive­ly.

In a post hoc analy­sis for a tar­get sub­group, the dif­fer­ence was even more promi­nent: +1.85, -0.15, and +16.27 let­ters, re­spec­tive­ly.

There was one se­ri­ous ad­verse event in the low dose arm, but jCyte said the grade 3 oc­u­lar hy­per­ten­sion re­solved with treat­ment and oth­er side ef­fects were gen­er­al­ly mi­nor.

CEO Paul Bres­ge not­ed that the tar­get sub­group analy­sis was in­tend­ed to ham­mer out the cri­te­ria they might use to re­cruit pa­tients in­to Phase III — which would like­ly have a sim­i­lar de­sign and use the same pri­ma­ry end­point of BC­VA, the “gold stan­dard in the con­text of FDA.” The late-stage tri­al is slat­ed for 2021.

“We did en­roll a very wide pa­tient pop­u­la­tion in­to our Phase IIb, in­clud­ing pa­tients that had vi­sion any­where from 20/80 to 20/800, just to learn which pa­tients would po­ten­tial­ly be the best re­spon­ders,” he said.

The tar­get sub­group is char­ac­ter­ized by hav­ing re­li­able fix­a­tion on the study eye, and a study eye that does not have sig­nif­i­cant­ly worse BC­VA (≤15 let­ters) than the fel­low eye.

He added that in­ves­ti­ga­tors al­so ob­served en­cour­ag­ing re­sults with the sec­ondary end­points such as low light mo­bil­i­ty, con­trast sen­si­tiv­i­ty ki­net­ic vi­su­al fields and a vi­sion func­tion ques­tion­naire, al­though the da­ta weren’t dis­closed.

“Typ­i­cal­ly peo­ple think about the dis­ease as a nar­row­ing of this pe­riph­er­al vi­sion in a very nice gran­u­lar way, but that’s ac­tu­al­ly not what hap­pens,” he said about the vi­su­al fields find­ing. “What hap­pens in the dis­ease is that pa­tients lose like is­lands of vi­sion. So what we’re do­ing in our tests is ac­tu­al­ly mea­sur­ing […] is­lands that the pa­tients have at base­line, and then what we’re see­ing af­ter treat­ment is that the is­lands are ex­pand­ing. It’s sim­i­lar to the way that one would track, let’s say a tu­mor, in on­col­o­gy of course we’re look­ing for the op­po­site ef­fect. We’re look­ing for the is­lands of vi­sion to ex­pand.”

The ther­a­py works pri­mar­i­ly by pre­serv­ing pho­tore­cep­tors, Klassen posits, not by gen­er­at­ing new ones. But what he thinks is hap­pen­ing is that pho­tore­cep­tors are re­gen­er­at­ing the out­er seg­ment — if pho­tore­cep­tors are ra­dios, these would be the an­ten­na — there­by re­gain­ing some func­tion.

That could po­si­tion it as a treat­ment for a dif­fer­ent stage of the dis­ease than Spark’s or Night­star’s. Klassen, who’s al­so re­search­ing reti­nal re­con­struc­tion us­ing stem cells, is hap­py to not view it through the com­pet­i­tive lens.

“If you look in­to the fu­ture, one could imag­ine that gene ther­a­pies will be most ef­fec­tive very ear­ly in the course of a dis­ease be­fore pho­tore­cep­tors are lost,” he said. “Then as pho­tore­cep­tors be­gin to be lost any­way, if that hap­pens, then a ther­a­py like ours would be­come ex­treme­ly valu­able. And if ours starts to lose pow­er late in the course of a dis­ease, maybe cell trans­plan­ta­tion un­der the reti­na could have a role.”

The Price of Re­lief: Ex­plor­ing So­lu­tions to the Ris­ing Costs of On­col­o­gy Drugs

In 2020, The National Cancer Institute estimated about 1.8 million new cases of cancer diagnosed in the United States, while the costs associated with treatment therapies continued to escalate. Given the current legislative climate on drug pricing, it’s never been more important to look at the evolution of drug pricing globally and control concerns of sustainable and affordable treatments in oncology.

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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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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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.

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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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