Roche is bring­ing back gan­tenerum­ab from the dead, tak­ing an­oth­er stab at Alzheimer’s PhI­II

Mar­lies Spro­ll, Mor­phoSys

Alzheimer’s drugs are ex­pen­sive to test and un­like­ly to suc­ceed, but they are al­so hard to kill.

More than two years af­ter gan­tenerum­ab failed de­ci­sive­ly in treat­ing ear­ly-stage Alzheimer’s, Roche is map­ping out an at­tempt­ed come­back through a new, piv­otal Phase III pro­gram that puts them back in­to the late-stage pipeline with their sec­ond ther­a­py.

In­ves­ti­ga­tors stub­born­ly vowed back at an in­ter­na­tion­al Alzheimer’s con­fer­ence in 2015 that if you amped up the dosage of the amy­loid be­ta an­ti­body it would be pos­si­ble to track a re­al treat­ment ef­fect for Alzheimer’s, im­prov­ing cog­ni­tion and func­tion. And now Roche part­ner Mor­phoSys, which con­tributed its plat­form tech in dis­cov­er­ing the drug, says the phar­ma gi­ant is go­ing for it — again.

The Ger­man biotech says that its con­tacts at Roche are plan­ning to launch two Phase III stud­ies in mild to pro­dro­mal pa­tients some­time lat­er in the year, stick­ing to a group of pa­tients who are just be­gin­ning to demon­strate symp­toms of the mem­o­ry-wast­ing ail­ment.

Roche nev­er gave up on gan­tenerum­ab. Roche neu­ro­science de­vel­op­ment chief Paulo Fon­toura tells me they’ve been us­ing two ex­tend­ed stud­ies to see if they can safe­ly use a much, much high­er dose need­ed to have an im­pact on the dis­ease with­out stir­ring up dan­ger­ous lev­els of ARIA-E, or brain swelling.

“We want­ed to find out if 4- or 5-fold (high­er dos­es) would be suc­cess­ful,” Fon­toura tells me, while con­trol­ling any cas­es of ARIA-E. And all in­di­ca­tions,he adds, is that they are on the right track.

Noth­ing has worked in Alzheimer’s R&D over the last 14 years, and gan­tenerum­ab looked like it would join a list of the most promi­nent drugs in the field to wash out of a big Phase III. But re­searchers have al­so been em­bold­ened by bet­ter di­ag­nos­tics to se­lect pa­tients as well as by the ear­ly da­ta from Bio­gen’s ad­u­canum­ab pro­gram which has shown glim­mers of ef­fi­ca­cy. Eli Lil­ly on­ly re­cent­ly wrapped its last piv­otal shot at solanezum­ab, its third straight fail­ure.

Mer­ck has al­so con­tributed to the drum­beat of fail­ures, re­cent­ly con­ced­ing de­feat in the most ad­vanced study of a BACE drug that tried to move up­stream in the dis­ease process, pre­vent­ing the pro­duc­tion of tox­ic lev­els of amy­loid be­ta. And Lund­beck flopped with its three Phase III stud­ies of their 5-HT6 an­tag­o­nist idalopir­dine, leav­ing Ax­o­vant as the last com­pa­ny to test that symp­to­matic ap­proach in a piv­otal study.

Why the ded­i­ca­tion? There are no drugs that can mod­i­fy the pro­gres­sion of Alzheimer’s and a big de­mand for any new symp­to­matic ther­a­pies that can slow the im­pact of the dis­ease, leav­ing the field wide open for a block­buster in­tro­duc­tion. And with every set­back, re­searchers in­sist that the same drugs could work un­der dif­fer­ent cir­cum­stances.

Now Roche will soon have two piv­otal pro­grams for Alzheimer’s back in the clin­ic, with gan­tenerum­ab run­ning along­side crenezum­ab.

“This is great news for Mor­phoSys. We are de­light­ed by the strong com­mit­ment to gan­tenerum­ab as a po­ten­tial new ther­a­py for Alzheimer’s dis­ease”, com­ment­ed Mar­lies Spro­ll, the chief sci­en­tif­ic of­fi­cer of Mor­phoSys AG. “The Hu­CAL-de­rived an­ti­body gan­tenerum­ab has prop­er­ties that we be­lieve make it a promis­ing can­di­date to treat Alzheimer’s dis­ease, and we look for­ward to learn­ing more about these new Phase III tri­als.”

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

So what hap­pened with No­var­tis' gene ther­a­py group? Here's your an­swer

Over the last couple of days it’s become clear that the gene therapy division at Novartis has quietly undergone a major reorganization. We learned on Monday that Dave Lennon, who had pursued a high-profile role as president of the unit with 1500 people, had left the pharma giant to take over as CEO of a startup.

Like a lot of the majors, Novartis is an open highway for head hunters, or anyone looking to staff a startup. So that was news but not completely unexpected.

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Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.

When ef­fi­ca­cy is bor­der­line: FDA needs to get more con­sis­tent on close-call drug ap­provals, agency-fund­ed re­search finds

In the exceedingly rare instances in which clinical efficacy is the only barrier to a new drug’s approval, new FDA-funded research from FDA and Stanford found that the agency does not have a consistent standard for defining “substantial evidence” when flexible criteria are used for an approval.

The research comes as the FDA is at a crossroads with its expedited-review pathways. The accelerated approval pathway is under fire as the agency recently signed off on a controversial new Alzheimer’s drug, with little precedent to explain its decision. Meanwhile, top officials like Rick Pazdur have called for a major push to simplify and clarify all of the various expedited pathways, which have grown to be must-haves for sponsors of nearly every newly approved drug.

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Ted White, Verrica CEO

Ver­ri­ca hits an­oth­er bump in the road with CMO re­lat­ed let­ter from FDA

The FDA has rejected Verrica’s new drug application for VP-102 again, with the company pinning the CRL on problems at a CMO that it was partnered with, the company announced Monday.

The FDA didn’t raise issues that directly relate to the manufacturing of VP-102, the company said, but raised “general quality issues” at the CMO’s facility. There were also no clinical concerns, it said, or need to collect more data.