Martine Rothblatt, United CEO (Jack Plunkett, AP Images)

Unit­ed ax­es PAH pro­gram Trevyent, once bought for cheap in ac­qui­si­tion of a ri­val, af­ter FDA feed­back

About three years af­ter ac­quir­ing SteadyMed and its ex­per­i­men­tal pul­monary ar­te­r­i­al hy­per­ten­sion drug Trevyent, Unit­ed Ther­a­peu­tics has de­cid­ed to kick the pro­gram to the curb.

In an 8-K form filed with the SEC on Tues­day, Unit­ed re­vealed that they are shut­ting down de­vel­op­ment of Trevyent af­ter re­ceiv­ing feed­back from the FDA last week. The move marks the end of a long and bumpy road for the pro­gram, which had pre­vi­ous­ly earned an RTF in 2017 and a CRL last April, as Unit­ed moves for­ward with new Ty­va­so for­mu­la­tions.

Reg­u­la­tors had di­rect­ed Unit­ed to both re­design the Trevyent prod­uct and con­duct an en­tire­ly new clin­i­cal study. That not on­ly would have added sig­nif­i­cant de­lays to the pro­gram, Unit­ed wrote, but may have proved un­suc­cess­ful in an­swer­ing the FDA’s con­cerns.

Specif­i­cal­ly, the FDA took is­sue with the prod­uct’s pump de­vice. Trevyent us­es a pump to de­liv­er a re­for­mu­lat­ed ver­sion of Unit­ed’s main­stay PAH drug Re­mod­ulin. The ac­cu­ra­cy of the pump, how­ev­er, was not up to snuff in reg­u­la­tors’ eyes, and Unit­ed said the agency want­ed the com­pa­ny to im­prove the ac­cu­ra­cy “in cer­tain re­spects.”

So Unit­ed has de­cid­ed to throw in the tow­el. They’re halt­ing all de­vel­op­ment of the pro­gram af­ter de­ter­min­ing it wouldn’t be com­mer­cial­ly rea­son­able to move for­ward. It marks an un­cer­e­mo­ni­ous end to a pro­gram they once picked up for a bar­gain from their com­peti­tors at SteadyMed in 2018.

With the $216 mil­lion buy­out, Unit­ed had been look­ing to head off a PAH clash be­tween the two com­pa­nies by ac­quir­ing Trevyent it­self. In ad­di­tion to that pro­gram, SteadyMed at the time had been try­ing to in­val­i­date one of Unit­ed’s patents for the ac­tive in­gre­di­ent in three of its promi­nent fran­chis­es: Re­mod­ulin, Ty­va­so and Oren­itram.

Though Unit­ed moved for­ward with Trevyent, sub­mit­ting its NDA to US reg­u­la­tors in Sep­tem­ber 2019, the agency re­ject­ed its pitch in an April 2020 CRL. The FDA had said that some of the de­fi­cien­cies pre­vi­ous­ly point­ed out had “not yet been ad­dressed to its sat­is­fac­tion,” Unit­ed said at the time. Unit­ed had been work­ing on a new pitch and Tues­day’s de­ci­sion stemmed from its sub­se­quent meet­ing with the FDA to re­sub­mit Trevyent for ap­proval.

It’s the lat­est in a cou­ple of pipeline set­backs Unit­ed has seen over the last few years. In 2019, the com­pa­ny dropped PAH hope­ful es­uber­aprost af­ter it failed a com­bo Phase III study, fail­ing to show ben­e­fit when com­bined with Ty­va­so over Unit­ed’s old­er Re­mod­ulin drug. Then, in Feb­ru­ary, Unit­ed re­vealed that a Phase II/III tri­al com­bin­ing their Uni­tux­in an­ti­body with a stan­dard treat­ment, irinote­can, failed to help small cell lung can­cer pa­tients live longer.

Unit­ed is in­stead mov­ing for­ward with an in­haled re­for­mu­la­tion of Ty­va­so af­ter snag­ging a pri­or­i­ty re­view vouch­er from Y-mAbs Ther­a­peu­tics last De­cem­ber for $105 mil­lion. The vouch­er had orig­i­nal­ly been slat­ed for Y-mAbs’ ap­pli­ca­tion for Danyelza in neu­rob­las­toma, and it wasn’t used for the FDA’s ap­proval in No­vem­ber.

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?

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.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

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.

Patrizia Cavazzoni, new CDER director

Pa­trizia Cavaz­zoni named per­ma­nent di­rec­tor of CDER, adding to ques­tions around where Wood­cock will end up

Patrizia Cavazzoni on Monday became the permanent director of the FDA’s Center for Drug Evaluation and Research, which puts to rest the idea that Janet Woodcock, Cavazzoni’s predecessor, might return to lead CDER if she isn’t made permanent commissioner.

Woodcock, who’s currently serving as acting commissioner and principal medical advisor to the commissioner, a position she was detailed to last year, may not make the move to permanent commissioner because of lingering questions from Senate Democrats. She previously served as director of CDER since 1994. Cavazzoni took over as acting director of CDER when Woodcock moved over to Operation Warp Speed to run the therapeutics side of the Trump-era program.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

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.’

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 106,500+ biopharma pros reading Endpoints daily — and it's free.

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.

Launched by MIT grads, a small start­up gets $20M to back a ro­bot­ics rev­o­lu­tion in cell ther­a­py man­u­fac­tur­ing

As co-director of an experimental cellular therapy process development and manufacturing group at UCSF specializing in T cell therapies for autoimmune conditions, Jonathan Esensten has learned a lot about the challenges involved when his group hand-fashions a cell therapy. Esensten — who was a postdoc in Wendell Lim’s lab and counts the legendary Jeffrey Bluestone as a mentor — gives them all high marks at being great at what they do, but time and again there are variations in the treatments they construct.

Barbara Weber, Tango Therapeutics CEO (Tango)

It takes two to Tan­go: The biotech us­ing CRISPR to dis­cov­er new can­cer gene tar­gets rides a $353M SPAC deal to Nas­daq

Editor’s note: Interested in following biopharma’s fast-paced IPO market? You can bookmark our IPO Tracker here.

The latest biotech-SPAC deal has arrived, and it’s dancing its way to Nasdaq to the tune of several hundred million dollars.

Tango Therapeutics and its CRISPR-focused search for new cancer genes is reverse merging with Boxer Capital’s blank-check company, the biotech announced Wednesday morning. With a spotlight on three lead programs, Tango expects total proceeds to equal about $353 million in the deal, which includes the roughly $167 million held in the SPAC and an additional $186 million in PIPE financing.

Kristin Fortney, BioAge Labs CEO

An­ti-ag­ing biotech up­start plucks a drug from Am­gen's dis­card pile, piv­ot­ing from heart fail­ure to mus­cle con­di­tions

Back in April 2019, Amgen quietly shut down a Phase I trial for a drug named AMG 986. There was no safety concern; the molecule just didn’t hit the mark on helping the small band of heart failure patients who received it.

A small biotech, though, believes it would stand a chance in the burgeoning anti-aging field.

BioAge Labs has licensed AMG 986 — now renamed BGE-105 — with plans to parlay the existing IND into a quick Phase I trial teasing out the pharmacodynamic effects and set the stage for mid-stage tests focused on acute muscle indications.