Io­n­is un­veils pos­i­tive PhII da­ta for in-house rare dis­ease drug, paving way to block­buster ri­val­ry with Take­da

One of the mid-stage an­ti­sense drugs for rare, non-neu­ro­log­i­cal dis­eases that Brett Mo­nia boast­ed about at JP Mor­gan ear­li­er this year has de­liv­ered a sol­id slate of pos­i­tive re­sults, boost­ing the CEO’s promise to turn Io­n­is in­to one of the biggest RNA biotechs with its whol­ly-owned pipeline.

With this par­tic­u­lar can­di­date, he may even be set­ting the com­pa­ny up for a ri­val­ry with Take­da.

The tri­al, which tests IO­N­IS-PKK-LRx in hered­i­tary an­gioede­ma, is small with 20 pa­tients. But the re­sults were un­equiv­o­cal: When you com­pare the 14 adults who re­ceived an 80mg month­ly dose of the drug to the six who got place­bo, you see a mean re­duc­tion of 90% in the num­ber of month­ly HAE at­tacks through weeks 1 to 17 in the study, meet­ing the pri­ma­ry end­point (p <0.001). From weeks five through 17 (one of the sec­ondary end­points), the mean re­duc­tion in month­ly at­tacks rose to 97% (p=0.003).

Dur­ing that short­er pe­ri­od, 92% of the 14 treat­ed with IO­N­IS-PKK-LRx were at­tack-free. None of the six pa­tients on place­bo reached that sta­tus (p <0.001).

A lig­and-con­ju­gat­ed an­ti­sense, IO­N­IS-PKK-LRx is de­signed to block prekallikrein, the pre­cur­sor to kallikrein, which in turn plays a key role in the ac­ti­va­tion of in­flam­ma­to­ry me­di­a­tors as­so­ci­at­ed with HAE at­tacks.

Kallikrein is the tar­get of Take­da’s block­buster con­tender Takhzy­ro (long­time ob­servers would re­mem­ber it as Shire’s lanadelum­ab), the first-ever drug to be ap­proved as a pro­phy­lac­tic for HAE. In late-stage tri­als, the an­ti­body had shown any­where from 73% to 87% re­duc­tion in those painful events.

For Stifel’s Paul Mat­teis, the topline da­ta from Io­n­is look promis­ing enough to po­ten­tial­ly com­pete with Take­da, es­pe­cial­ly giv­en that it has an “in­cre­men­tal­ly bet­ter dos­ing reg­i­men” of quar­ter­ly ad­min­is­tra­tion ver­sus every two to four weeks.

If the re­sults hold up in lat­er tri­als, that is. From the an­a­lyst note:

There are still a few things we don’t know here, in­clud­ing pa­tient base­line sever­i­ty, or col­or on AE rates. But head­ing in­to this cat­a­lyst, we had viewed the com­pet­i­tive bar as quite high giv­en Lanadelum­ab’s ro­bust ef­fi­ca­cy (an 80%+ re­duc­tion in HAE at­tacks); by com­par­i­son, PKK-LRx gen­er­at­ed a ~90% re­duc­tion in HAE at­tacks, and even bet­ter ef­fi­ca­cy than this af­ter the 5 week time-point. The sam­ple size for the Io­n­is study isn’t huge (N=20) and in re­al­i­ty the drugs are prob­a­bly more sim­i­lar than dif­fer­ent–these PKK da­ta are re­al­ly sim­i­lar to the lanadelum­ab ph1b when the drug was “DX2930”. But bot­tom line, this looks like a nice win for Io­n­is, for a drug they could take for­ward in­de­pen­dent­ly.

That last part is sig­nif­i­cant for Io­n­is. Stan­ley Crooke spent years team­ing up with big­ger drug­mak­ers that an­ti­sense could be a pow­er­ful RNA-based ap­proach for ma­nip­u­lat­ing gene ex­pres­sion, with a promi­nent ex­am­ple in the Bio­gen-part­nered spinal mus­cu­lar at­ro­phy block­buster drug Spin­raza. Af­ter some or­ga­ni­za­tion en­gi­neer­ing that in­volved spin­ning out the com­mer­cial port­fo­lio to Akcea, Mo­nia is ready to go it alone with nu­mer­ous late-stage can­di­dates to push past the fin­ish line on their own.

“In every­thing out­side of the liv­er — es­pe­cial­ly neu­ro, in pul­monary — we’re 100% dif­fer­en­ti­at­ed right now,” Mo­nia told End­points News at the vir­tu­al JPM con­fer­ence this Jan­u­ary.

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?

Voting in the 2020 election (AP Images)

The right to vote is fun­da­men­tal — a let­ter from biotech­nol­o­gy in­dus­try lead­ers

Biotech Voices is a collection of exclusive opinion editorials from some of the leading voices in biopharma on the biggest industry questions today. Think you have a voice that should be heard? Reach out to senior editors Kyle Blankenship and Amber Tong.

We oppose all attempts to introduce laws that reduce the rights of US citizens to vote or that restrict them from exercising that right. The right to vote is fundamental to democracy. States that have enacted, or are proposing to enact, legislation to restrict voting are undermining our democracy and posing a threat to our nation. As leaders of the life sciences industry, we stand for what we believe is right for our country, our enterprises, our employees and those who benefit from our work. We join the first groups of business leaders who have challenged these laws and will continue to make our collective voices heard on this matter.

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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Sajith Wickramasekara, Benchling via YouTube

Meet Bench­ling, the lat­est uni­corn seek­ing to rev­o­lu­tion­ize the way sci­en­tists do work with the help of the cloud

There’s another unicorn in biotech land, as Benchling and its leading R&D cloud platform pull in a $200 million Series E to help scientists accelerate drug development. In doing so, the company hit a lofty $4 billion valuation — nearly five times what it was worth around this time last year, according to Forbes.

Despite the fact that drug development is becoming significantly more complex, the industry continues to run on paper, emails and spreadsheets, co-founder and CEO Sajith Wickramasekara said in a video on Benchling’s website. The MIT grad sought to change that by creating software that allows scientists to better track, model and forecast their work.

Covid-19 roundup: No­vavax shakes up lead­er­ship with two pro­mo­tions and de­par­ture of CFO; Mod­er­na, No­vavax shots added to mix-and-match study in the UK

Novavax has had a busy month, filled with supply chain issues and manufacturing deals that have affected the rollout of its Covid-19 vaccine. Tuesday, the company announced updates to its leadership team.

CFO Greg Covino will step down from that role after just five months for personal reasons, the release said, but take on a new role as executive advisor. John Trizzino, current chief commercial officer and chief business officer, will take the CFO role over in the interim.

Amy­lyx to move for­ward with ALS pro­gram in Eu­rope, but FDA wants an­oth­er look; Hu­ma­cyte adds $50M in debt fi­nanc­ing

Amylyx is one of several companies looking to break through in the tough ALS field, and Wednesday they announced they’re moving forward with regulatory plans.

The Cambridge, MA-based biotech said they’re submitting a marketing application to the EMA for their AMX0035 program by the end of 2021. Wednesday’s news comes a few weeks after they revealed similar plans to move forward with Canadian health regulators by June 30.

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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UP­DAT­ED: J&J paus­es vac­cine roll­out as feds probe rare cas­es of blood clots

The FDA and CDC have jointly decided to stop administering J&J’s Covid-19 vaccine after reviewing data involving six reported US cases of a rare and severe type of blood clot in individuals after receiving the vaccine.

CDC will convene a meeting of its Advisory Committee on Immunization Practices on Wednesday to further review these cases and assess their potential significance. “FDA will review that analysis as it also investigates these cases. Until that process is complete, we are recommending a pause in the use of this vaccine out of an abundance of caution,” Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research and Anne Schuchat, Principal Deputy Director of the CDC, said in a joint statement Tuesday morning.

Anand Shah (FDA)

For­mer head of FDA’s med­ical and sci­en­tif­ic af­fairs on Covid: ‘FDA has nev­er been test­ed like this’

Anand Shah has served the American public in a unique way, crisscrossing over the last two administrations between serving as an attending radiation oncologist focused on prostate cancer at NIH, serving as CMO at the Center for Medicare and Medicaid Innovation, and most recently, leading the FDA’s operations on medical and scientific affairs from within the commissioner’s office.

Shah, who stepped down from the FDA in January, caught up with Endpoints News in a phone interview on Tuesday afternoon, offering his thoughts on the agency’s latest decision to pause the J&J vaccinations in the US, and reflecting on his time at an agency during this once-in-a-lifetime pandemic.