Court sides with FDA in Van­da clin­i­cal hold suit

The US Dis­trict Court for the Dis­trict of Co­lum­bia on Fri­day ruled in the FDA’s fa­vor in a case brought by Van­da Phar­ma­ceu­ti­cals con­cern­ing a par­tial clin­i­cal hold placed on a study of the com­pa­ny’s in­ves­ti­ga­tion­al drug tradip­i­tant in De­cem­ber 2018.

In the de­ci­sion, Judge John Bates de­nied Van­da’s mo­tions for sum­ma­ry judge­ment and re­fused to al­low the fil­ing of an am­i­cus brief by the Hu­mane So­ci­ety that chal­lenged the FDA’s jus­ti­fi­ca­tion for an ad­di­tion­al an­i­mal study.

In a state­ment Fri­day, Van­da said it is re­view­ing the de­ci­sion and “will de­ter­mine the ap­pro­pri­ate next steps.”

Back­ground

The dis­pute cen­ters on the FDA’s de­ci­sion to place a hold on a 52-week open-la­bel ex­ten­sion to a Phase II study of tradip­i­tant to treat gas­tro­pare­sis un­til Van­da con­duct­ed a nine-month non­ro­dent tox­i­c­i­ty study to sup­port the use of the drug in hu­mans be­yond 12 weeks.

In April 2018, Van­da first sought a 52-week ex­ten­sion to its ini­tial four week Phase II study but re­duced the ex­ten­sion to eight weeks af­ter the FDA said it did not have enough safe­ty da­ta to sup­port tradip­i­tant’s use in hu­mans be­yond three months.

Van­da sought to ex­tend the study by 52 weeks twice more in 2018 be­fore the FDA placed a par­tial clin­i­cal hold on the tri­al, in­sist­ing that nine-month non­ro­dent tox­i­c­i­ty stud­ies “are re­quired … per the [In­ter­na­tion­al Coun­cil for Har­mon­i­sa­tion] ICH Guid­ance for In­dus­try : M3(R2) Non­clin­i­cal Safe­ty Stud­ies for the Con­duc­tion of Hu­man Clin­i­cal Tri­als and Mar­ket­ing Au­tho­riza­tion for Phar­ma­ceu­ti­cals.”

On 5 Feb­ru­ary 2019, Van­da sued the FDA over the par­tial clin­i­cal hold, al­leg­ing that the FDA failed “to ar­tic­u­late an ad­e­quate sci­en­tif­ic ba­sis” for the hold and in­sist­ing that the rec­om­men­da­tions in the ICH guid­ance are non-bind­ing. In re­sponse to the suit, FDA asked the court for a vol­un­tary re­mand to “ad­dress cer­tain pro­ce­dur­al is­sues” in the com­plaint.

Af­ter re­view­ing Van­da’s pro­pos­als, the FDA is­sued a re­sponse con­clud­ing that “ex­ist­ing tradip­i­tant stud­ies in non­ro­dents con­tain suf­fi­cient trou­bling in­di­ca­tions of tox­i­c­i­ty such that—while short­er-term hu­man stud­ies may be safe enough to pro­ceed—FDA needs to see if those tox­i­c­i­ty mark­ers in­crease dur­ing long-term non­ro­dent stud­ies be­fore al­low­ing long-term hu­man stud­ies,” and pro­vid­ing a sci­en­tif­ic ra­tio­nale for its re­quest for a nine-month non­ro­dent study.

Anal­y­sis

In the de­ci­sion, Bates re­ject­ed Van­da’s ar­gu­ment that the jus­ti­fi­ca­tion for the clin­i­cal hold made in the FDA’s re­mand re­sponse is “im­per­mis­si­ble post hoc ra­tio­nal­iza­tion,” find­ing that the re­mand re­sponse was made by prop­er de­ci­sion­mak­ers at the FDA and that the re­sponse ap­pro­pri­ate­ly ex­pand­ed on the agency’s ear­li­er de­ci­sion.

The judge al­so re­ject­ed Van­da’s as­ser­tion that the FDA “se­lec­tive­ly opened the record up­on re­mand, adding new stud­ies that sup­port its po­si­tion but fail­ing to add stud­ies ref­er­enced in Van­da’s com­plaint or in a let­ter mailed by the Hu­mane So­ci­ety.” Ac­cord­ing to the rul­ing, “the re­mand mo­tion did not re­quire FDA to con­sid­er ad­di­tion­al ev­i­dence from Van­da; (2) no le­gal au­thor­i­ty re­quired FDA to con­sid­er ad­di­tion­al ev­i­dence form Van­da or the Hu­mane So­ci­ety; and (3) Van­da de­lib­er­ate­ly de­clined to take ad­van­tage of the ad­min­is­tra­tive means avail­able for in­tro­duc­ing its de­sired ev­i­dence in­to the record.”

Van­da’s claim that the FDA ap­plied the ICH guid­ance as a bind­ing leg­isla­tive rule is al­so tossed out. “Though some of FDA’s com­ments pre-re­mand sug­gest­ed that the ICH Guid­ance im­posed a ‘re­quire­ment’ on Van­da, even the ini­tial clin­i­cal hold let­ter did not re­ly on the ICH Guid­ance as the le­gal source of au­thor­i­ty—in­stead, it cit­ed the con­trol­ling reg­u­la­tion as the ba­sis for the hold,” the judge wrote, not­ing that the ICH guid­ance “is a gen­er­al pol­i­cy state­ment” and not a leg­isla­tive rule re­quir­ing a no­tice-and-com­ment rule­mak­ing process.

Ad­di­tion­al­ly, the judge re­ject­ed Van­da’s as­ser­tion that the FDA failed to demon­strate that ca­nine stud­ies are pre­dic­tive of ef­fects in hu­mans.

“Van­da’s ar­gu­ment is un­per­sua­sive for the ba­sic rea­son that the statu­to­ry and reg­u­la­to­ry scheme here ex­plic­it­ly con­tem­plates that the re­sults of an­i­mal stud­ies are pre­dic­tive of the re­sults of hu­man tri­als,” the judge wrote.


RAPS: First pub­lished in Reg­u­la­to­ry Fo­cus™ by the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety, the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care prod­ucts. Click here for more in­for­ma­tion.

The 20 un­der 40: In­side the next gen­er­a­tion of bio­phar­ma lead­ers

“Each generation needs a new music,” Francis Crick wrote in 1988, reflecting back on his landmark discovery. Crick was 35, then, in 1953, when he began working with a 23-year-old named James Watson, and 37 when the pair unveiled the double helix. Rosalind Franklin, whose diffraction work undergirded their metal model, was 32.

The model would become the score for a new era in biology, one devoted to cracking the basic structures turning inside life. Subsequent years would bring new conductors and new rhythms: Robert Swanson, 29 when he convinced a 39-year-old Herb Boyer to build a company off his work and call it Genentech; Phillip Sharp, 29 when he discovered RNA splicing and 34 when he co-founded Biogen; Frances Arnold, 36 when she pioneered directed evolution; Feng Zhang, 31 when he published his CRISPR paper.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 77,700+ biopharma pros reading Endpoints daily — and it's free.

Chart-top­ping ven­ture cash? Strong deal flow? In the month Covid-19 ripped around the globe? Yup

It turns out that even sending everyone from the CEO to rank-and-file staffers home to work in the middle of a Category 5 pandemic wasn’t enough to put a crimp in the flow of venture cash into biopharma. And even dealmaking held its own against the howling winds of misfortune — largely because a group of savvy players was quick to adjust to the new reality.

Our deal expert Chris Dokomajilar ran the numbers for us on a month-to-month basis and found that not only was venture money flowing during the panicky month of March, but it was also hitting home in record sums compared to the last 26 months of deal flow.

Say what?

As you can see in the top chart below, Dokomajilar outlined how the industry racked up $2.41 billion in total for March, just barely ahead of one other topper during the heady days of August 2018.

Endpoints Premium

Premium subscription required

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

FDA Commissioner Stephen Hahn and President Donald Trump at a press briefing on March 19, 2020. (AP Images)

Biotech ex­ecs warn that the FDA is fum­bling their re­sponse to the Covid-19 open-door promise, de­lay­ing progress

A few days ago the FDA touted a procedure for Covid-19 meds that committed the agency to immediate action for developers, formalizing a high-speed response that’s been promised for weeks.

Bioregnum Opinion Column by John Carroll

Decisions that once required months would be measured in hours under the Coronavirus Treatment Acceleration Program. “In many cases” trial protocols could be hammered out in less than a single day. If you had a potential solution to the crisis, the appropriate staffer would be in touch “to get studies underway quickly.”

It would be the ultimate high-speed regulatory pathway from Phase I to approval. Red tape was banished.

But it’s clear that for some — and quite likely many — biopharma execs, the actual agency response has not measured up to the promise. Beyond the front ranks of advanced companies in the field, like Gilead, or for drugs endorsed by President Trump, it may not even come close.

“The first response is this form letter everyone gets,” says one biotech CEO who’s reached out to the FDA on Covid-19. And when you try to cut through that, the ball gets dropped as it is passed from top officials to the frontline staff actually charged with getting things done.

Endpoints Premium

Premium subscription required

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

GSK's Hal Bar­ron buys a $250M stake in George Scan­gos' Vir and makes a bee­line to the clin­ic with Covid-19 an­ti­bod­ies

GlaxoSmithKline is diving straight into the swirling waters of Covid-19 R&D work, and investing $250 million to grab a chunk of equity in one of the emerging stars in infectious disease research to make it official.

GSK put out word this morning that it is partnering with Vir Biotechnology $VIR, the infectious disease startup founded in the Bay Area by former Biogen CEO George Scangos. They’re planning a leap into Phase II studies for 2 preclinical antibody candidates — VIR-7831 and VIR-7832 — that have been engineered to target the SARS-CoV-2 spike protein.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 77,700+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: A small, ob­scure biotech just won big with their IPO. In this mar­ket. Are you kid­ding me?

How could a small, largely unknown biotech that emerged from stealth mode just months ago with early-stage cancer programs jump onto Wall Street in the middle of a Category 6 financial hurricane and sail through with a $165 million IPO?

And what does that mean for the rest of the industry waiting to see just how much damage global lockdowns will wreak on clinical development?

The biotech is a company called Zentalis. The crew there nabbed an $85 million crossover round late last year — notably waiting 5 years before waving the numbers around to attract attention, according to my read of a FierceBiotech story. Perceptive joined in, but the syndicate was not in general the kind of marquee affair that gets tongues wagging.

Endpoints Premium

Premium subscription required

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

Ready to de­clare a de­fin­i­tive come­back in two months, Im­munomedics stops PhI­II ear­ly, re­cruits new CEO

More than a year ago, hit by a surprise complete response letter from the FDA, Immunomedics bid its then-CEO, Michael Pehl, adieu and began a 15-month quest to resolve the manufacturing issues cited in the CRL and seek a new leader — all the while moving forward with a Phase III study on its lead drug for metastatic triple-negative breast cancer.

Today the biotech said their stars are finally aligning. Not only is Novartis Oncology vet Harout Semerjian coming on board as CEO to steer what they believe will be a smooth sail to a new PDUFA date in June, Immunomedics has also been informed that their late-stage trial can be stopped early due to “compelling evidence of efficacy.”

An­oth­er day, an­oth­er boat­load for biotech. Deer­field adds $840M to rush of ven­ture dol­lars

The biotech dollars just keep rolling in.

Even as the world economy faces an economic contraction unprecedented in nature, biotech venture capital firms are announcing huge new investment pots. The latest? Deerfield Management Co.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 77,700+ biopharma pros reading Endpoints daily — and it's free.

Small mol­e­cules, bi­o­log­ics and now gene ther­a­pies: Ger­many's Evotec adds an­oth­er feath­er to its R&D cap

German drug discovery company Evotec — which has a thriving rolodex of biopharma partners such as Bayer, Boehringer Ingelheim, Novartis, Novo Nordisk, Pfizer, Sanofi, and Takeda — is now venturing into gene therapies.

The company swallowed Seattle-based Just Biotherapeutics, a company focused on reducing the cost of manufacturing protein therapies last year. It is now setting up a dedicated R&D site for gene therapies in Austria, in an effort to achieve a “modality-agnostic” repertoire — small molecules, biologics and now gene therapies.

A pair of PhI­II fail­ures spells last rites for Men­lo’s once-promis­ing Mer­ck drug

Four months after an intercontinental merger, Menlo Therapeutics is counting yet another pair of trial failures — ones with significant consequences for the companies, their shareholders and the drug.

In two pivotal Phase III trials, Menlo’s lead drug serlopitant failed to treat pruritus associated with prurigo nodularis — basically itchiness from a particular skin disease that causes red lesions on a person’s arms or legs. Serlopitant has long been the company’s only drug and as recently as 2018, it looked promising enough to support a stock price of $37. In April of that year, a Phase II failure demolished the stock price overnight: $35 to $9. Other subsequent stumbles trickled the ticker down to just above $2.