Ear­ly sur­vival da­ta boost Zio­phar­m's 'con­trolled IL-12' im­munother­a­py for glioblas­toma

An un­con­ven­tion­al pair­ing of a gene ther­a­py and an oral drug that promis­es to at­tack re­cur­rent or pro­gres­sive glioblas­toma with con­trolled re­lease of IL-12 has turned up more promis­ing — if ear­ly — over­all sur­vival da­ta. On top of boost­ing its case as a monother­a­py, the da­ta can al­so bode well for a com­bi­na­tion with Re­gen­eron’s PD-1 in­hibitor, Lib­tayo.

Both the treat­ment and its de­vel­op­er, Zio­pharm On­col­o­gy, have come a long way. The stock price peaked in 2015 but cratered in 2016 fol­low­ing a pa­tient death in a Phase I.

Lau­rence Coop­er

Long-term fol­low-up da­ta from the study, though, sug­gest that Ad-RTS-hIL-12 plus veled­imex (Ad+V) is not on­ly safe but helps pa­tients live be­yond a year. Across the main and ex­pan­sion stud­ies, the sub­group of pa­tients re­ceiv­ing the low-dose cor­ti­cos­teroids — to­tal­ing 20 — showed me­di­an over­all sur­vival of 16.2 months.

“We know from con­ver­sa­tions with reg­u­la­tors that me­di­an over­all sur­vival (mOS) is used as a bench­mark to help de­ter­mine the po­ten­tial ap­proval of new treat­ments for re­cur­rent (rGBM),” CEO Lau­rence Coop­er told End­points News. “There­fore, this sur­vival end­point is what we are us­ing to gauge suc­cess of our Con­trolled IL-12 can­di­date.”

His­tor­i­cal­ly, uni­fo­cal re­cur­rent glioblas­toma mul­ti­forme pa­tients on­ly live for 6 to 12 months, he added, mean­ing there’s a 30% “ad­di­tion” of life for pa­tients.

By in­ject­ing a vec­tor that car­ries the gene for IL-12 — a pow­er­ful in­ter­leukin that’s re­ferred to as a “mas­ter cy­tokine” for its abil­i­ty to or­ches­trate an im­mune re­sponse — Zio­pharm’s goal is to stir up T cell re­sponse against hard-to-treat can­cer. But to en­sure that the im­mune sys­tem doesn’t get out of con­trol, the biotech has in­vent­ed an oral ac­ti­va­tor lig­and such that physi­cians can tune how much IL-12 to re­lease, by re­mote­ly in­struct­ing the pa­tients to ad­just the dose.

Cor­ti­cos­teroids pro­vide an ex­tra lev­el of pro­tec­tion, al­though it could al­so damp­en the im­mune ac­tiv­i­ty — which Coop­er said ex­plains why the pa­tients on the low­est dose of steroids seem to have the best re­sponse to their ther­a­py.

In­ves­ti­ga­tors have pre­vi­ous­ly not­ed in­creased check­point sig­nal­ing, an ob­ser­va­tion that led them to test a com­bi­na­tion of Ad+V and nivolum­ab (Op­di­vo). At 8.3 months of me­di­an fol­low-up, mOS has not been reached. Re­gen­eron has signed on to test the com­bo ap­proach with its own PD-1 drug, and the Phase II study is on­go­ing.

The lat­est up­date across three tri­als al­so brought the tal­ly of par­tial re­spons­es to five.

“Ob­serv­ing re­spons­es in brain tu­mors in the set­ting of re­cur­rence is un­usu­al and high­ly en­cour­ag­ing, and, along with the sur­vival da­ta, high­light the po­ten­tial of Ad+V for the treat­ment of rGBM,” said An­to­nio Chioc­ca, a tri­al in­ves­ti­ga­tor based at Dana-Far­ber and Brigham and Women’s Hos­pi­tal.

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

FDA commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.

The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

Samit Hirawat (Bristol Myers Squibb)

Af­ter bruis­ing re­jec­tion, blue­bird and Bris­tol My­ers Squibb land ide-cel pri­or­i­ty re­view. But will it mat­ter for the CVR?

With the clock all but up, the FDA accepted and handed priority review to Bristol Myers Squibb and bluebird bio’s BCMA CAR-T, keeping a narrow window open for Celgene investors to still cash in on the $9 CVR from the $63 billion Celgene merger.

The acceptance comes five months after the two companies weres slammed with a surprise refuse-to-file that threatened to foreclose the CVR entirely. Today’s acceptance sets the FDA decision date for March 27, 2021 – or precisely 4 days before the CVR deadline of March 31. Given the breakthrough designation and strong pivotal data — 81.5% response rate, 35.2% complete response rate — priority review was largely expected.

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Blueprint CEO Jeff Albers (file photo)

Blue­print plots re­turn to FDA with new Ay­vak­it da­ta in rare con­di­tion — and the an­a­lysts cheer

Over a decade after launch, Blueprint Medicines nabbed the first approval for their first drug earlier this year. Now, as they move forward with a Roche-partnered global launch, they’re touting data that could push them into more patients.

The Jeff Albers-led Cambridge biotech released their full pivotal data for Ayvakit in patients with advanced systemic mastocytosis. In one 53-person study, they showed that 76% of patients responded to the drug, 36% had complete responses and that on average their responses lasted for just over 3 years. A smaller, 32-patient study had a 75% response rate and most were still responding after 10.4 months, the last follow-up.

#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.

Can a mag­net­ic cell ther­a­py re­place corneal trans­plan­ta­tion? As eight-year jour­ney leads to the clin­ic, two broth­ers un­veil bold vi­sion

Jeff Goldberg was getting acquainted with a brand new way to do corneal transplants when an even newer, even bolder idea hit him.

It was almost 10 years ago, and Goldberg was in his first faculty position at Bascom Palmer Eye Institute at the University of Miami. Scientists had developed a new way to do cornea transplants where instead of sewing a whole donor cornea — a decades-old practice — they were just engrafting the inner layer of cells.

Anthony Coyle (Repertoire)

Flag­ship's merged biotech Reper­toire nets ex-Pfiz­er CSO An­tho­ny Coyle as R&D chief

Flagship is building a big-name C-suite at its new, $220 million merged biotech.

Repertoire Immune Medicines, which already boasts former Bioverativ chief John Cox as its CEO, announced yesterday that Anthony Coyle, the former Pfizer CSO and the founding CEO of Pandion, will join as their head of R&D.

“As we progress clinical trials for our multi-clonal T cell candidates in immuno-oncology, Tony’s deep expertise in cellular immunology and novel therapeutic development will help us achieve our vision of creating a new class of transformative medicines for patients,” Cox said in a statement.

President Donald Trump (via AP Images)

Signs of an 'Oc­to­ber Vac­cine Sur­prise' alarm ca­reer sci­en­tists. HHS con­tin­ues to claim Azar “will de­fer com­plete­ly to the FDA"

President Donald Trump, who seems intent on announcing a Covid-19 vaccine before Election Day, could legally authorize a vaccine over the objections of experts, officials at the FDA and even vaccine manufacturers, who have pledged not to release any vaccine unless it’s proved safe and effective.

In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Trump — who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA — will take matters into his own hands, running roughshod over the usual regulatory process.