Richard Wilson, Astellas SVP, primary focus lead – genetic regulation

Fol­low­ing clin­i­cal hold lift, Astel­las posts ear­ly Pompe gene ther­a­py da­ta

Fresh out of a clin­i­cal hold, Astel­las is spot­light­ing da­ta on its gene ther­a­py for Pompe dis­ease.

In four pa­tients who got an in­fu­sion of the gene ther­a­py, called AT845, three dis­con­tin­ued en­zyme re­place­ment ther­a­py. As of the Sept. 15 cut­off, those three pa­tients have been off en­zyme re­place­ment ther­a­py for 19, 44 and 51 weeks, re­spec­tive­ly.

Astel­las did not bring any da­ta on the pri­ma­ry ef­fi­ca­cy end­point — en­zyme ex­pres­sion and ac­tiv­i­ty — though it did present sec­ondary ef­fi­ca­cy da­ta. The three par­tic­i­pants who were tak­en off ERT main­tained sim­i­lar re­sults in forced vi­tal ca­pac­i­ty, a mea­sure of lung ca­pac­i­ty, af­ter stop­ping bi­week­ly treat­ments. In ad­di­tion, two of the three had con­sis­tent re­sults on a six-minute walk test af­ter be­ing tak­en off ERT. The third saw a de­crease in dis­tance walked on the test af­ter they de­vel­oped a case of pe­riph­er­al neu­ropa­thy.

The ear­ly-stage dose es­ca­la­tion tri­al is test­ing AT845 in adult late-on­set Pompe dis­ease pa­tients. Two pa­tients got a low dose of the ther­a­py (3×1013 vg/kg), while two got a high­er dose that was dou­ble that (6×1013 vg/kg). The one pa­tient who re­mains on en­zyme re­place­ment ther­a­py got the low dose, Astel­las gene reg­u­la­tion leader Richard Wil­son told End­points News.

AT845 is meant to de­liv­er a copy of the gene for an en­zyme called GAA via a vi­ral vec­tor to mus­cle tis­sues. Peo­ple with Pompe lack the en­zyme, lead­ing to sug­ars build­ing up and dam­ag­ing the mus­cles. Cur­rent­ly, the stan­dard of care for the ge­net­ic dis­ease is a bi­week­ly in­fu­sion of one of two en­zyme re­place­ment ther­a­pies — My­ozyme/Lu­mizyme and its suc­ces­sor Nexvi­azyme — both de­vel­oped by Sanofi’s Gen­zyme.

Astel­las hopes its gene ther­a­py can pro­vide a longer-term treat­ment for the dis­ease.

How­ev­er, the gene ther­a­py pro­gram was put on clin­i­cal hold in June af­ter one of the high dose pa­tients de­vel­oped pe­riph­er­al sen­so­ry neu­ropa­thy. That hold was lift­ed in late Jan­u­ary. Up­on lift­ing the hold, Astel­las said that it was un­able to con­clude whether the neu­ropa­thy case was re­lat­ed to its drug.

Three of the four par­tic­i­pants had high lev­els of liv­er en­zymes, which have been seen in oth­er gene ther­a­pies de­liv­ered via vi­ral vec­tors as well. All three cas­es were re­solved with changes to im­mune sup­pres­sion, Astel­las said.

The FDA told Astel­las to con­tin­ue dos­ing its next two pa­tients at the high­er dose of 6×1013 vg/kg, Wil­son not­ed.

Wil­son al­so point­ed to re­sults on a fa­tigue ques­tion­naire, where three of the four pa­tients saw their fa­tigue scores trend to­ward im­prove­ment. “This in­di­cates an im­por­tant fact that these pa­tients have start­ed to demon­strate some mea­sures of feel­ing a lit­tle bet­ter,” he said. “I don’t want to mis­char­ac­ter­ize that or over-promise it, but, from what we’re hear­ing from the PI, we feel that these im­prove­ments in fa­tigue are ac­tu­al­ly mean­ing­ful to pa­tients.”

Wil­son said that Astel­las hopes to re­sume dos­ing in the com­ing weeks to months.

Forge Bi­o­log­ics’ cGMP Com­pli­ant and Com­mer­cial­ly Vi­able Be­spoke Affin­i­ty Chro­matog­ra­phy Plat­form

Forge Biologics has developed a bespoke affinity chromatography platform approach that factors in unique vector combinations to streamline development timelines and assist our clients in efficiently entering the clinic. By leveraging our experience with natural and novel serotypes and transgene conformations, we are able to accelerate affinity chromatography development by nearly 3-fold. Many downstream purification models are serotype-dependent, demanding unique and time-consuming development strategies for each AAV gene therapy product1. With the increasing demand to propel AAV gene therapies to market, platform purification methods that support commercial-scale manufacturing of high-quality vectors with excellent safety and efficacy profiles are essential.

Feng Zhang (Susan Walsh/AP Images)

In search of new way to de­liv­er gene ed­i­tors, CRISPR pi­o­neer turns to mol­e­c­u­lar sy­ringes

Bug bacteria are ruthless.

Some soil bacteria have evolved tiny, but deadly injection systems that attach to insect cells, perforate them and release toxins inside — killing a bug in just a few days’ time. Scientists, on the other hand, want to leverage that system to deliver medicines.

In a paper published Wednesday in Nature, MIT CRISPR researcher Feng Zhang and his lab describe how they engineered these syringes made by bacteria to deliver potential therapies like toxins that kill cancer cells and gene editors. With the help of an AI program, they developed syringes that can load proteins of their choice and selectively target human cells.

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Luke Miels, GSK chief commercial officer

GSK picks up Scynex­is' FDA-ap­proved an­ti­fun­gal drug for $90M up­front

GSK is dishing out $90 million cash to add an antifungal drug to its commercial portfolio, in a deal spotlighting the pharma giant’s growing focus on infectious diseases.

The upfront will lock in an exclusive license to Scynexis’ Brexafemme, which was approved in 2021 to treat a yeast infection known as vulvovaginal candidiasis, except in China and certain other countries where Scynexis already out-licensed the drug.

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See­los Ther­a­peu­tics 'tem­porar­i­ly' stops study in rare neu­ro dis­or­der for busi­ness rea­sons

Microcap biotech Seelos Therapeutics is halting enrollment of its study in spinocerebellar ataxia type 3 (also known as Machado-Joseph disease) because of “financial considerations,” and in order to focus on other studies, the company said today, adding that the pause would be temporary.

The study will continue with the patients who have already enrolled, and the data from them will be used to decide whether to continue enrolling others in the future.

Alec­tor cuts 11% of work­force as it dou­bles down on late-stage neu­ro pro­grams part­nered with GSK, Ab­b­Vie

A month after revealing plans to concentrate on its late-stage immuno-neurology pipeline, Alector is trimming its headcount by 11%.

The layoffs will impact around 30 employees across the organization, the company disclosed in an SEC filing, adding that the plan will “better align the company’s resources” with the new strategy. With $712.9 million in cash, cash equivalents and investments as of the end of 2022, Alector believes the reserves will now get it through 2025.

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Mathai Mammen, FogPharma's next CEO

Math­ai Mam­men hands in J&J's R&D keys to lead Greg Ver­dine’s Fog­Phar­ma 

In the early 1990s, Mathai Mammen was a teaching assistant in Greg Verdine’s Science B46 course at Harvard. In June, the former R&D head at Johnson & Johnson will succeed Verdine as CEO, president and chair of FogPharma, the same month the seven-year-old biotech kickstarts its first clinical trial.

After leading R&D at one of the largest drugmakers in the world, taking the company through more than half a dozen drug approvals in the past few years, not to mention a Covid-19 vaccine race, Mammen departed J&J last month and will take the helm of a Cambridge, MA biotech attempting to go after what Verdine calls the “true emperor of all oncogenes” — beta-catenin.

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J&J bows out of RSV vac­cine race, end­ing PhI­II study and ced­ing to Pfiz­er, GSK

Johnson & Johnson announced Wednesday morning it is ending development of its adult RSV vaccine that was in the middle of a 27,200-patient trial, giving up a big slice of what’s expected to be the next multibillion-dollar pharma market.

The decision came down to the shifting RSV “competitive landscape,” a company spokesperson tells Endpoints News, adding the “breadth of options” was much different than when J&J first started its pivotal study. The spokesperson declined to comment on the Phase III data, saying only the shot is undergoing an “ongoing assessment.”

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No longer ‘dead or just hi­ber­nat­ing,’ drug­mak­ers re­turn to heart med­i­cines

In 2015, now-FDA Commissioner Robert Califf joined industry, academic and regulatory representatives in Washington to discuss why more drugs weren’t in development for cardiovascular diseases, the leading US cause of death and once a mainstay of pharmaceutical industry blockbusters.

The group pointed to many reasons. Clinical trials could take years and testing was expensive. Wide availability of generic drugs made the commercial prospects uncertain. Their paper title summed up the mood: “Cardiovascular Drug Development: Is it Dead or Just Hibernating?”

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Mihael Polymeropoulos, Vanda Pharmaceuticals CEO

Van­da wins court case against FDA over dis­clo­sure of CRL de­tails for sleep drug

DC District Court Judge Christopher Cooper today granted Vanda Pharma’s request to require the FDA to disclose more info on the complete response letter for its sleep disorder drug Hetlioz.

The melatonin receptor agonist is approved by the FDA to treat non-24-hour sleep-wake disorder, a circadian rhythm disorder. But in 2018 Vanda filed a supplemental application to market Hetlioz as a treatment for jet lag, which the FDA rejected in August 2019, with few details on what Vanda needed to correct course, according to the company.