Af­ter ear­ly hic­cups in man­u­fac­tur­ing, Ad­verum out­lines plans for com­mer­cial gene ther­a­py plant in North Car­oli­na hub

Af­ter some ear­ly hic­cups in its man­u­fac­tur­ing pro­ce­dures for its gene ther­a­py drug tar­get­ing wet age-re­lat­ed mac­u­lar de­gen­er­a­tion, Cal­i­for­nia biotech Ad­verum has ad­dressed those con­cerns and is prim­ing the pump for a com­mer­cial launch.

The oc­u­lar and oth­er rare dis­ease-fo­cused gene ther­a­py com­pa­ny will in­vest $80 mil­lion in a new cGMP man­u­fac­tur­ing fa­cil­i­ty in North Car­oli­na’s bustling Re­search Tri­an­gle Park that by 2023 will be ready to man­u­fac­ture com­mer­cial sup­ply of AD­VM-022, Ad­verum’s in­trav­it­re­al ther­a­peu­tic, the com­pa­ny said Thurs­day.

The 174,000 square-foot fa­cil­i­ty will in­clude four 1,000-liter biore­ac­tors, with space for fu­ture ex­pan­sion, and will cre­ate more than 200 jobs. In ad­di­tion to its $80 mil­lion in­vest­ment, Ad­verum will gain up to $9 mil­lion in North Car­oli­na state and lo­cal in­cen­tives.

An­gela Thedin­ga

“Our new in-house com­mer­cial man­u­fac­tur­ing fa­cil­i­ty sets the foun­da­tion of our over­all man­u­fac­tur­ing strat­e­gy,” An­gela Thedin­ga, Ad­verum’s chief tech­nol­o­gy of­fi­cer, said in a state­ment. “Our new site will pro­vide ded­i­cat­ed com­mer­cial sup­ply, while we con­tin­ue to lever­age CMO part­ner­ships for flex­i­ble clin­i­cal and ad­di­tion­al com­mer­cial sup­ply.”

In 2020, Phase I tri­al da­ta from AD­VM-022 start­ed to turn a cor­ner af­ter some weak read­outs in the past. In­ves­ti­ga­tors in May re­port­ed that two of three co­horts con­tin­ued to re­spond to treat­ment, with the ma­jor­i­ty still free of the need for res­cue in­jec­tions, while the third co­hort ex­pe­ri­enced few­er side ef­fects than oth­er an­ti-VEGF ther­a­peu­tics.

Lau­rent Fis­ch­er

The year 2019 was more dif­fi­cult for the biotech. In April of that year, the FDA im­posed a clin­i­cal hold on the ap­pli­ca­tion to test AD­VM-022 in hu­mans, ask­ing Ad­verum for more da­ta on the chem­istry, man­u­fac­tur­ing and con­trol process, End­points News re­port­ed. The hold was lift­ed short­ly af­ter.

Then in Sep­tem­ber, Ad­verum re­vealed da­ta that in­di­cat­ed pa­tients with AMD saw their vi­sion de­te­ri­o­rate when treat­ed with AD­VM-022, de­spite signs that the treat­ment was im­prov­ing reti­nal anato­my. Those pa­tients who saw a vi­sion de­te­ri­o­ra­tion lost vi­su­al acu­ity by two let­ters on av­er­age in a 90% con­fi­dence in­ter­val of -9.1 let­ters to +5.1 let­ters, the com­pa­ny re­port­ed from the 24-week OP­TIC tri­al.

In late 2019, the biotech al­so aban­doned de­vel­op­ment of its then-lead ex­per­i­men­tal drug, AD­VM-043, for treat­ing A1AT de­fi­cien­cy.

In a press re­lease an­nounc­ing Ad­verum’s new fa­cil­i­ty, CEO Lau­rent Fis­ch­er was down­right bull­ish on the com­pa­ny’s fu­ture.

“We are build­ing a team with ex­cep­tion­al AAV-gene ther­a­py ex­pe­ri­ence and we are thrilled to join the high­ly-skilled and di­verse North Car­oli­na biotech com­mu­ni­ty,” he said. “This state-of-the-art fa­cil­i­ty will sup­port our com­mer­cial­iza­tion of AD­VM-022, the po­ten­tial first mass mar­ket­ed gene ther­a­py for wet AMD and DME.”

BY­OD Best Prac­tices: How Mo­bile De­vice Strat­e­gy Leads to More Pa­tient-Cen­tric Clin­i­cal Tri­als

Some of the most time- and cost-consuming components of clinical research center on gathering, analyzing, and reporting data. To improve efficiency, many clinical trial sponsors have shifted to electronic clinical outcome assessments (eCOA), including electronic patient-reported outcome (ePRO) tools.

In most cases, patients enter data using apps installed on provisioned devices. At a time when 81% of Americans own a smartphone, why not use the device they rely on every day?

Image: Shutterstock

Eli Lil­ly asks FDA to re­voke EUA for Covid-19 treat­ment

Eli Lilly on Friday requested that the FDA revoke the emergency authorization for its Covid-19 drug bamlanivimab, which is no longer as effective as a combo therapy because of a rise in coronavirus variants across the US.

“With the growing prevalence of variants in the U.S. that bamlanivimab alone may not fully neutralize, and with sufficient supply of etesevimab, we believe now is the right time to complete our planned transition and focus on the administration of these two neutralizing antibodies together,” Daniel Skovronsky, Lilly’s CSO, said in a statement.

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J&J faces CDC ad­vi­so­ry com­mit­tee again next week to weigh Covid-19 vac­cine risks

The CDC’s Advisory Committee on Immunization Practices punted earlier this week on deciding whether or not to recommend lifting a pause on the administration of J&J’s Covid-19 vaccine, but the committee will meet again in an emergency session next Friday to discuss the safety issues further.

The timing of the meeting likely means that the J&J vaccine will not return to the US market before the end of next week as the FDA looks to work hand-in-hand with the CDC to ensure the benefits of the vaccine still outweigh the risks for all age groups.

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Osman Kibar (Samumed, now Biosplice)

Os­man Kibar lays down his hand at Sa­mumed, step­ping away from CEO role as his once-her­ald­ed an­ti-ag­ing biotech re­brands

Samumed made quite the entrance back in 2016, when it launched with some anti-aging programs and a whopping $12 billion valuation. That level of fanfare was nowhere to be found on Thursday, when the company added another $120 million to its coffers and quietly changed its name to Biosplice Therapeutics.

Why the sudden rebrand?

“We did that for obvious reasons,” CFO and CBO Erich Horsley told Endpoints News. “The name Biosplice echoes our science much more than Samumed does.”

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Ex­clu­sive in­ter­view: Pe­ter Marks on why full Covid-19 vac­cine ap­provals could be just months away

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, took time out of his busy schedule last Friday to discuss with Endpoints News all things related to his work regulating vaccines and the pandemic.

Marks, who quietly coined the name “Operation Warp Speed” before deciding to stick with his work regulating vaccines at the FDA rather than join the Trump-era program, has been the face of vaccine regulation for the FDA throughout the pandemic, and is usually spotted in Zoom meetings seated in front of his wife’s paintings.

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Near­ly a year af­ter Au­den­tes' gene ther­a­py deaths, the tri­al con­tin­ues. What hap­pened re­mains a mys­tery

Natalie Holles was five months into her tenure as Audentes CEO and working to smooth out a $3 billion merger when the world crashed in.

Holles and her team received word on the morning of May 5 that, hours before, a patient died in a trial for their lead gene therapy. They went into triage mode, alerting the FDA, calling trial investigators to begin to understand what happened, and, the next day, writing a letter to alert the patient community so they would be the first to know. “We wanted to be as forthright and transparent as possible,” Holles told me late last month.

The brief letter noted two other patients also suffered severe reactions after receiving a high dose of the therapy and were undergoing treatment. One died a month and a half later, at which point news of the deaths became public, jolting an emergent gene therapy field and raising questions about the safety of the high doses Audentes and others were now using. The third patient died in August.

“It was deeply saddening,” Holles said. “But I was — we were — resolute and determined to understand what happened and learn from it and get back on track.”

Eleven months have now passed since the first death and the therapy, a potential cure for a rare and fatal muscle-wasting disease called X-linked myotubular myopathy, is back on track, the FDA having cleared the company to resume dosing at a lower level. Audentes itself is no more; last month, Japanese pharma giant Astellas announced it had completed working out the kinks of the $3 billion merger and had restructured and rebranded the subsidiary as Astellas Gene Therapies. Holles, having successfully steered both efforts, departed.

Still, questions about precisely what led to the deaths of the 3 boys still linger. Trial investigators released key details about the case last August and December, pointing to a biological landmine that Audentes could not have seen coming — a moment of profound medical misfortune. In an emerging field that’s promised cures for devastating diseases but also seen its share of safety setbacks, the cases provided a cautionary tale.

Audentes “contributed in a positive way by giving a painful but important example for others to look at and learn from,” Terry Flotte, dean of the UMass School of Medicine and editor of the journal Human Gene Therapy, told me. “I can’t see anything they did wrong.”

Yet some researchers say they’re still waiting on Astellas to release more data. The company has yet to publish a full paper detailing what happened, nor have they indicated that they will. In the meantime, it remains unclear what triggered the events and how to prevent them in the future.

“Since Audentes was the first one and we don’t have additional information, we’re kind of in a holding pattern, flying around, waiting to figure out how to land our vehicles,” said Jude Samulski, professor of pharmacology at UNC’s Gene Therapy Center and CSO of the gene therapy biotech AskBio, now a subsidiary of Bayer.

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Pascal Soriot (AstraZeneca via YouTube)

Af­ter be­ing goad­ed to sell the com­pa­ny, Alex­ion's CEO set some am­bi­tious new goals for in­vestors. Then Pas­cal So­ri­ot came call­ing

Back in the spring of 2020, Alexion $ALXN CEO Ludwig Hantson was under considerable pressure to perform and had been for months. Elliott Advisers had been applying some high public heat on the biotech’s numbers. And in reaching out to some major stockholders, one thread of advice came through loud and clear: Sell the company or do something dramatic to change the narrative.

In the words of the rather dry SEC filing that offers a detailed backgrounder on the buyout deal, Alexion stated: ‘During the summer and fall of 2020, Alexion also continued to engage with its stockholders, and in these interactions, several stockholders encouraged the company to explore strategic alternatives.’

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Abzena picks North Car­oli­na as the home for its 6th man­u­fac­tur­ing site, plans to add 325 jobs in San­ford

While Boston and San Francisco are the unquestioned leading biotech hubs in the US, drugmakers — particularly contract manufacturers — are looking elsewhere for cheaper real estate and untapped potential. Now, a San Diego-based biologics maker looking to rapidly scale up is setting down roots in North Carolina.

CDMO Abzena will add 325 jobs in Sanford, NC, as part of a $200 million biologics plant that will eventually house around 24,000 square feet of bioreactor capacity, the company said.

Geoff MacKay, Avrobio

Avro­bio is us­ing 'pod­s' to cre­ate gene ther­a­pies, and it be­lieves the ap­proach could change the game al­to­geth­er

Where other companies have gone big, Avrobio is going small. Its manufacturing operation is no different.

Instead of trying to keep up with the validation of new facilities — and spending money and precious time in the process — the company has opted for a different approach: small, automated pods that can be installed in rented clean rooms anywhere. Though production output isn’t as high as other companies, Avrobio avoids brick-and-mortar and is able to stay flexible and nimble to respond to fluctuations.