Kenji Yasukawa, Astellas CEO (Akio Kon/Bloomberg via Getty Images)

FDA lifts clin­i­cal hold on Astel­las’ Pompe gene ther­a­py

The FDA has lift­ed a clin­i­cal hold on Astel­las Phar­ma’s Pompe dis­ease gene ther­a­py tri­al, the Japan­ese com­pa­ny an­nounced Fri­day morn­ing. The FDA put the hold in place last June af­ter in­ves­ti­ga­tors flagged a se­ri­ous case of sen­so­ry nerve dam­age in a pa­tient.

Astel­las says it is mak­ing strides to­ward re­sum­ing dos­ing in the Phase I/II clin­i­cal tri­al for adult pa­tients with late-on­set Pompe dis­ease, in which they lack an en­zyme called GAA that breaks down com­plex sug­ars in the body, caus­ing said sug­ars to build up and dam­age the mus­cles. Astel­las’ head of reg­u­la­to­ry af­fairs David Smethurst de­clined to com­ment on when the tri­al would re­sume dos­ing.

The gene ther­a­py, dubbed AT845, was de­signed to de­liv­er a copy of the GAA gene via an AAV8 vec­tor to mus­cle tis­sues. It would pro­vide a one-time al­ter­na­tive to en­zyme re­place­ment ther­a­pies Lu­mizyme/My­ozyme and Nexvi­azyme, all de­vel­oped by Sanofi and the lat­ter ap­proved in 2021.

Last June, the FDA paused Astel­las’ Pompe tri­al, say­ing it didn’t have enough in­for­ma­tion to as­sess the risk to pa­tients fol­low­ing the safe­ty sig­nal. The ad­verse event was clas­si­fied as Grade 1 (mean­ing it was mild), but was deemed se­ri­ous due to med­ical sig­nif­i­cance. Smethurst said in an email it was “not pos­si­ble to say with cer­tain­ty what caused the pe­riph­er­al sen­so­ry neu­ropa­thy.”

Smethurst not­ed in his email a num­ber of changes to the Pompe gene ther­a­py tri­al de­sign. “The main changes to the pro­to­col in­clude the ex­clu­sion of par­tic­i­pants with his­to­ry of risk fac­tors for neu­ropa­thy, as well as ad­di­tion­al neu­ro­log­i­cal as­sess­ments and mon­i­tor­ing through­out the study. We are al­so propos­ing to in­crease the du­ra­tion be­tween dos­ing the next two pa­tients in FOR­TIS and the re­main­der of the dose co­hort, to per­mit ad­di­tion­al safe­ty mon­i­tor­ing,” he wrote.

The safe­ty sig­nal and tri­al pause were part of a grow­ing num­ber of sim­i­lar ex­am­ples fac­ing gene ther­a­pies that are de­liv­ered via vi­ral vec­tors called AAVs. Astel­las it­self presided over one of the most se­ri­ous cas­es. The com­pa­ny’s gene ther­a­py unit is built around a 2019 buy­out of Au­dentes Ther­a­peu­tics, but it stopped its lead pro­gram from that pur­chase af­ter three pa­tients died — and then lat­er a fourth af­ter Astel­las restart­ed the pro­gram with a low­er dose and more safe­ty mea­sures — af­ter re­ceiv­ing a gene ther­a­py for X-linked my­otubu­lar my­opa­thy, or XLMTM, a rare mus­cle weak­ness dis­ease.

Re­searchers and reg­u­la­tors alike are grap­pling with how to safe­ly de­liv­er these ther­a­pies, as AAVs re­main one of the pri­ma­ry ways to pack­age and de­liv­er genes to the right or­gans. Some biotechs are try­ing to de­vel­op new ver­sions of AAVs, while oth­ers are es­chew­ing the vi­ral vec­tors en­tire­ly, search­ing for non-vi­ral de­liv­ery meth­ods (and some are work­ing some­where in be­tween).

This sto­ry was up­dat­ed with com­ment from David Smethurst.

Trodelvy notch­es a win in most com­mon form of breast can­cer

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.

Sen. Ron Wyden (D-OR) (Francis Chung/E&E News/Politico via AP Images)

In­fla­tion re­bates in­com­ing: Wyden calls on CMS to move quick­ly as No­var­tis CEO pledges re­ver­sal

Senate Finance Chair Ron Wyden (D-OR) this week sent a letter to the head of the Centers for Medicare & Medicaid Services seeking an update on how and when new inflation-linked rebates will take effect for drugs that see major price spikes.

The newly signed Inflation Reduction Act requires manufacturers to pay a rebate to Medicare when they increase drug prices faster than the rate of inflation.

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David Kirn, 4D Molecular Therapeutics CEO (via website)

FDA places hold on 4D Mol­e­c­u­lar’s Fab­ry gene ther­a­py

4D Molecular Therapeutics quietly tucked an FDA clinical hold on its Fabry gene therapy into an SEC filing.

Meanwhile, the biotech issued a press release the same day after the closing bell on Thursday touting an IND for another asset, in diabetic macular edema.

The California biotech had paused enrollment of patients in its two trials of the Fabry gene therapy (4D-310) last month after three patients experienced kidney issues, all of which were resolved within four weeks. At the time, 4DMT said it would wait until the second half of this year to look at 12-month clinical data on six patients in the Phase I/II trials, one in the US and one in Taiwan and Australia.

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Uğur Şahin, BioNTech CEO (Andreas Arnold/picture-alliance/dpa/AP Images)

BioN­Tech opens new plas­mid DNA man­u­fac­tur­ing fa­cil­i­ty in Ger­many

German mRNA player BioNTech opened the doors to a new manufacturing facility on Thursday, this one just about 75 miles north of its headquarters in Mainz, Germany.

BioNTech announced on Thursday that it has completed the construction of its first plasmid DNA manufacturing facility in Marburg, Germany. The facility will produce materials for mRNA-based vaccines and therapies along with cell therapies.

Teresa Graham, incoming Roche Pharmaceuticals CEO

In­com­ing Roche CEO builds out his top team, tap­ping Genen­tech vet to lead phar­ma di­vi­sion

Roche announced another leadership shuffle Thursday morning – the head of global product strategy, Teresa Graham, will take over as CEO of Roche Pharmaceuticals in March while the company’s corporate executive committee will make a spot for Levi Garraway, CMO and executive VP of global product development.

Thomas Schinecker will take over the top spot as Roche group CEO in March, leaving his spot as head of diagnostics.

FDA ap­proves GSK's ane­mia drug with safe­ty warn­ing — af­ter bat­ting back sim­i­lar drugs

GSK has secured the first of four US approvals it’s hoping for this year, as the FDA greenlit daprodustat as a treatment for anemia due to chronic kidney disease.

But the FDA limited the use of the drug, to be marketed as Jesduvroq, to patients who have been receiving dialysis for at least four months and stopped short of approving it for patients not dependent on dialysis — in line with the recommendations of the advisory committee it consulted.

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Raymond Stevens, Structure Therapeutics CEO

Be­hind Fri­day's $161M IPO: A star sci­en­tist, GPCR drug dis­cov­ery and a plan to chal­lenge phar­ma in di­a­betes

What does it take to pull off a $161 million biotech IPO these days?

In Structure Therapeutics’ case, it means having a star scientist co-founder paired with the computational drug discovery company Schrödinger, $198 million in private funding from blue-chip investors, almost six years of research work on G protein-coupled receptors and a slate of oral, small-molecule drugs, with an eye on the huge and growing diabetes and weight-loss market.

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Af­ter 13 years, Ramy Mah­moud steps in­to CEO seat at Opti­nose; Ru­pert Vessey set to ex­it Bris­tol My­ers in Ju­ly

After 13 years as president and COO at Optinose, Ramy Mahmoud has stepped into a new role as its CEO. He is taking the place of Peter Miller, who stepped down earlier this week, though Miller is still staying with the company as a consultant.

In 2010, the two business partners joined Optinose to take it in a new direction, transforming it from a delivery platform to product company. They previously worked together at Johnson & Johnson, when Miller was president at Janssen and Mahmoud headed medical affairs. Miller said after he learned about Optinose, “I did what I always do, which is find people smarter than me to talk with about the idea. And the first person I called was Ramy … and I said, ‘Hey, Ramy, what do you think of this technology?’”

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Te­va drops out of in­dus­try trade group PhRMA

Following in AbbVie’s footsteps, Teva confirmed on Friday that it’s dropping out of the industry trade group Pharmaceutical Research and Manufacturers of America (PhRMA).

Teva didn’t give a reason for its decision to leave, saying only in a statement to Endpoints News that it annually reviews “effectiveness and value of engagements, consultants and memberships to ensure our investments are properly seated.”

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