FDA forces trou­bled Ad­vax­is to halt en­roll­ment on its PhI­II study for lead drug ax­al­imo­gene

A lit­tle more than a month af­ter Am­gen qui­et­ly walked away from its $65 mil­lion up­front to part­ner with Ad­vax­is $ADXS on ax­al­imo­gene filolis­bac, the biotech is re­port­ing that the FDA has slapped the pro­gram with a par­tial hold or­der­ing a stop to new en­roll­ment in the Phase III. And this isn’t the first time.

Ac­cord­ing to the com­pa­ny’s re­lease, reg­u­la­tors trig­gered the hold on their study for cer­vi­cal can­cer due to “re­quests for ad­di­tion­al in­for­ma­tion per­tain­ing to cer­tain AX­AL chem­istry, man­u­fac­tur­ing and con­trols (CMC) mat­ters.” No new safe­ty is­sues were iden­ti­fied, ac­cord­ing to the biotech.

Now a pen­ny stock biotech, Ad­vax­is shares closed at just 31 cents to­day, down 10%. And the shares dropped 15% more af­ter the news hit.

Ad­vax­is is ad­vanc­ing ther­a­pies that use live at­ten­u­at­ed Lis­te­ria mono­cy­to­genes which are en­gi­neered to se­crete anti­gen/ad­ju­vant fu­sion pro­teins. And they’re not sim­ple to de­vel­op. The ther­a­py us­es bac­te­ria to kick up an im­mune re­sponse by trig­ger­ing a T cell at­tack on can­cer cells.

Ken­neth Berlin

“FDA’s re­view of the AX­AL In­ves­ti­ga­tion­al New Drug (IND) ap­pli­ca­tion was prompt­ed by our pro­pos­al to mod­i­fy the AIM2CERV tri­al’s analy­sis plan to in­clude, among oth­er things, al­lowance for a sec­ond for­mal in­ter­im analy­sis for both safe­ty and ef­fi­ca­cy,” said Ken­neth Berlin, Ad­vax­is’ CEO. “The pri­ma­ry fo­cus of the items raised by the Agency re­lates to pro­vid­ing ad­di­tion­al clar­i­fy­ing de­tails for CMC in­for­ma­tion pre­vi­ous­ly pro­vid­ed in sup­port of Phase 3 de­vel­op­ment and which will help sup­port a fu­ture Bi­o­log­ics Li­cense Ap­pli­ca­tion. We have al­ready be­gun ef­forts to ad­dress the Agency’s re­quests for in­for­ma­tion and are work­ing to re­spond as prompt­ly as we can.”

That event fol­lows an ear­li­er clin­i­cal hold on their lead pro­gram in com­bi­na­tion with As­traZeneca’s PD-L1 check­point Imfinzi fol­low­ing a pa­tient death, though the hold was lat­er lift­ed. Af­ter a months-long holdup in H1 2018, re­searchers came up with new guide­lines aimed at pre­vent­ing any fu­ture in­stances of acute res­pi­ra­to­ry fail­ure that killed the pa­tient.

No­var­tis reshuf­fles its wild cards; Tough sell for Bio­gen? Googling pro­teins; Ken Fra­zier's new gig; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

If you enjoy the People section in this report, you may also want to check out Peer Review, my colleagues Alex Hoffman and Kathy Wong’s comprehensive compilation of comings and goings in biopharma.

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Demis Hassabis, DeepMind CEO (Qianlong/Imaginechina via AP Images)

Google's Deep­Mind opens its pro­tein data­base to sci­ence — po­ten­tial­ly crack­ing drug R&D wide open

Nearly a year ago, Google’s AI outfit DeepMind announced they had cracked one of the oldest problems in biology: predicting a protein’s structure from its sequence alone. Now they’ve turned that software on nearly every human protein and hundreds of thousands of additional proteins from organisms important to medical research, such as fruit flies, mice and malaria parasite.

The new database of roughly 350,000 protein sequences and structures represents a potentially monumental achievement for the life sciences, one that could hasten new biological insights and the development of new drugs. DeepMind said it will be free and accessible to all researchers and companies.

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Vas Narasimhan, Novartis CEO (Jason Alden/Bloomberg via Getty Images)

No­var­tis dis­cards one of its ‘wild card’ drugs af­ter it flops in key study. But it takes one more for the hand

Always remember just how risky it is to gamble big on small studies.

A little more than 4 years ago, Novartis reportedly put up a package worth up to $1 billion for the dry eye drug ECF843 after a small biotech called Lubris put it through its paces in a tiny study of 40 moderate to severe patients, tracking some statistically significant markers of efficacy.

By last fall, the program had risen up to become one of CEO Vas Narasimhan’s top “wild card” programs in line for a potential breakthrough year in 2021. These drugs were all considered high-risk, high-reward efforts. And in this case, risk won.

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6 top drug­mak­ers of­fer per­spec­tives on FDA's new co­vari­ates in RCTs guid­ance

Back in May, the FDA revised and expanded a 2019 draft guidance that spells out how to adjust for covariates in the statistical analysis of randomized controlled trials.

Building on the ICH’s E9 guideline on the statistical principles for clinical trials, the 3-page draft was transformed into an 8-page draft, with more detailed recommendations on linear and nonlinear models to analyze the efficacy endpoints in RCTs.

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In­side Bio­gen's scram­ble to sell Aduhelm: Pro­ject 'Javelin' and pres­sure to ID as many pa­tients as pos­si­ble

In anticipation of Aduhelm’s approval for Alzheimer’s in June, Biogen employees were directed to identify and guarantee treatment centers would administer the drug through a program called “Javelin,” a senior Biogen employee told Endpoints News.

The program identified about 800 centers for use, he said, and Biogen now pays for the use of bioassays to identify beta amyloid in potential patients having undergone a lumbar puncture procedure, the employee said — and one center preparing to administer the drug confirmed its participation in the bioassay program.

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EMA re­jects FDA-ap­proved Parkin­son's drug, signs off on Mod­er­na vac­cine use in ado­les­cents ahead of FDA

The European Medicines Agency on Friday rejected Kyowa Kirin’s Parkinson’s disease drug Nouryant (istradefylline), which the US FDA approved in 2019 under the brand name Nourianz.

EMA said it considered that the results of the clinical studies used to support the application “were inconsistent and did not satisfactorily show that Nouryant was effective at reducing the ‘off’ time. Only four out of the eight studies showed a reduction in ‘off’ time, and the effect did not increase with an increased dose of Nouryant.”

Laurent Fischer, Adverum CEO

Ad­verum faces murky fu­ture af­ter re­view turns up deep­er safe­ty is­sues for gene ther­a­py

Three months after revealing that a patient lost significant vision in one eye after receiving its experimental gene therapy, Adverum announced it found the safety issues were more widespread: Five of 12 patients who received a high dose of the therapy saw “similar clinically-relevant events.”

Three required surgery on their treated eye. And all 12 are being recommended “aggressive immunomodulatory treatments” to prevent further injury.

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Mol­e­c­u­lar Di­ag­nos­tics Can Trans­form Can­cer Care. Let’s Make It Hap­pen.

Like so many people around the world, my life has been profoundly shaped by cancer. Those personal experiences, along with a deep love of clinical laboratory science and a passion to apply the power of genomics in medicine, motivated me to launch a company that would improve cancer care through better diagnostics. Thirteen years later, I am proud that we are delivering more accurate information at multiple points along the patient journey, with a focus on eight of the 10 cancers that are most commonly diagnosed in the United States.

FDA lev­els clin­i­cal hold on Ma­gen­ta's sec­ond lead drug, ask­ing for an ad­di­tion­al bioas­say be­fore it gets to hu­mans

Earlier this summer, Magenta Therapeutics was forced to say goodbye to its head of R&D at a pivotal time as the biotech read out data for its lead stem cell conditioning hopeful. Just weeks later, the company’s second drug is facing a clinical hold from the FDA as the agency demands more info on how the candidate works in humans.

Magenta will be required to submit an additional bioassay to help determine the best path forward on dose escalation for the biotech’s Phase I/II study of MGTA-117, an antibody-drug conjugate used to deplete hematopoietic stem cells prior to a transplant of HSC-based gene therapy, the biotech said Wednesday.

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