Eli Lil­ly con­ducts an au­top­sy of an Alzheimer’s megaflop

For four years Eli Lil­ly $LLY com­mit­ted one of the biggest clin­i­cal ef­forts in the com­pa­ny’s his­to­ry to prov­ing that it could get solanezum­ab right on Alzheimer’s. Hav­ing nav­i­gat­ed through mul­ti­ple tri­al fail­ures al­ready, in­ves­ti­ga­tors were con­vinced that if they took what they had learned, changed the pa­tient pop­u­la­tion, stick­ing to on­ly pa­tients with a mild form of the dis­ease while us­ing bet­ter di­ag­nos­tics — even chang­ing the end­points in the lead up to the fi­nal read out — they could make a case that this drug could make a sig­nif­i­cant im­prove­ment for pa­tients.

In­stead, they came up with a set of mod­est fig­ures in­di­cat­ing that at best they had mere­ly tapped the brakes on the dis­ease. And to­day they spelled it all out in what will like­ly be the post mortem on what once fac­tored in as one of the biggest clin­i­cal gam­bles in the his­to­ry of bio­phar­ma.

Solanezum­ab was de­signed to flush amy­loid be­ta, a tox­ic pro­tein which of­ten clus­ters in the brains of Alzheimer’s vic­tims. The in­ves­ti­ga­tors of­fered some mixed mes­sages on just how ef­fec­tive so­la was in re­duc­ing a-be­ta de­posits. In­ves­ti­ga­tor tracked sig­nif­i­cant changes in plas­ma lev­els of the pro­tein, but check­ing amy­loid de­posits with PET imag­ing pro­duced no sig­nif­i­cant changes. Re­searchers in oth­er pro­grams will be fol­low­ing that close­ly as they make their own as­saults on amy­loid, which re­mains a key fo­cus. There is a grow­ing con­sen­sus in the field, though, that it will take com­bi­na­tion ther­a­pies to have a re­al im­pact on the mem­o­ry-wast­ing dis­ease that af­flicts mil­lions.

Look­ing for a dom­i­nant new block­buster, they had to set­tle for en­cour­ag­ing pa­tients to hope for some­thing bet­ter.

Lawrence S. Honig, MD, PhD, Co­lum­bia

“Alzheimer’s is a chal­leng­ing dis­ease that re­searchers have been com­mit­ted to study­ing for some years,” said Lawrence S. Honig, MD, PhD, pro­fes­sor of neu­rol­o­gy at Co­lum­bia Uni­ver­si­ty Med­ical Cen­ter and prin­ci­pal in­ves­ti­ga­tor of the EX­PE­DI­TION3 study, pre­sent­ed the da­ta at the meet­ing. “Now is not the time to give up. While the out­come of this study is not what we had hoped for, it is rea­son­able to be­lieve that dis­ease mod­i­fy­ing ther­a­pies to slow down the pro­gres­sion of Alzheimer’s dis­ease will be dis­cov­ered.”

The key fail­ure point was on ADAS-Cog14, which mea­sures a per­son’s cog­ni­tive func­tions, in­clud­ing mem­o­ry, at­ten­tion and lan­guage abil­i­ties. In­ves­ti­ga­tors tracked an 11% re­duc­tion in the rate of de­cline, a clear miss with a p-val­ue of .095.

The sec­ondary end­points weren’t that much dif­fer­ent.

  • There was the Mi­ni-Men­tal State Ex­am­i­na­tion, or MMSE, with a 13% slow­ing in cog­ni­tive de­cline.
  • The Clin­i­cal De­men­tia Rat­ing-Sum of Box­es (CDR-SB) scale showed a 15 per­cent slow­ing in de­cline (p=0.004) be­tween pa­tients treat­ed with solanezum­ab and pa­tients treat­ed with place­bo.
  • There was a 14 per­cent slow­ing of de­cline (p=.019) as mea­sured by the Alzheimer’s Dis­ease Co­op­er­a­tive Study- In­stru­men­tal Ac­tiv­i­ties of Dai­ly Liv­ing (AD­CS-iADL). The AD­CS-iADL scale mea­sures a per­son’s in­de­pen­dent per­for­mance in com­plex ac­tiv­i­ties of dai­ly liv­ing such as par­tic­i­pat­ing in a con­ver­sa­tion, prepar­ing a meal or shop­ping.
  • The Func­tion­al Ac­tiv­i­ties Ques­tion­naire did not show a sta­tis­ti­cal­ly sig­nif­i­cant dif­fer­ence be­tween pa­tients treat­ed with solanezum­ab and pa­tients treat­ed with place­bo (7 per­cent re­duc­tion in de­cline, p=0.140). The FAQ scale is a dif­fer­ent in­for­mant-based mea­sure of func­tion­al abil­i­ties. In­for­mants pro­vide per­for­mance rat­ings of the pa­tient on ten com­plex high­er-or­der ac­tiv­i­ties.

There was, though, a greater chance that the drug arm would suf­fer from spinal os­teoarthri­tis: 1.1 per­cent in the solanezum­ab group, 0.4 per­cent in the place­bo group. And there was a 0.9 per­cent rate of dy­suria in the solanezum­ab group.

In the mean­time, you can rack up an­oth­er set­back in a field that has known on­ly late-stage fail­ure in the past decade.

Tal Zaks, Moderna CMO (Moderna via YouTube)

UP­DAT­ED: NI­AID and Mod­er­na spell out a 'ro­bust' im­mune re­sponse in PhI coro­n­avirus vac­cine test — but big ques­tions re­main to be an­swered

The NIAID and Moderna have spelled out positive Phase I safety and efficacy data for their Covid-19 vaccine mRNA-1273 — highlighting the first full, clear sketch of evidence that back-to-back jabs at the dose selected for Phase III routinely produced a swarm of antibodies to the virus that exceeded levels seen in convalescent patients — typically in multiples indicating a protective response.

Moderna execs say plainly that this first stage of research produced exactly the kind of efficacy they hoped to see in humans, with a manageable safety profile.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 85,300+ biopharma pros reading Endpoints daily — and it's free.

Trans­port Sim­u­la­tion Test­ing for Your Ther­a­py is the Best Way to As­sure FDA Ex­pe­dit­ed Pro­gram Ap­proval

Modality Solutions is an ISO:9001-registered biopharmaceutical cold chain engineering firm with unique transport simulation capabilities that support accelerated regulatory approval for biologics and advanced therapeutic medicinal products (ATMP). Our expertise combines traditional validation engineering approaches with regulatory knowledge into a methodology tailored for the life sciences industry. We provide insight and execution for the challenges faced in your cold chain logistics network.

Source: Shutterstock

Who are the women blaz­ing trails in bio­phar­ma R&D and lead­ing the fight against Covid-19? Nom­i­nate them for End­points' spe­cial re­port

One of the many inequalities the pandemic has laid bare is the gender imbalance in biomedical research. A paper examining Covid-19 research authorship wondered out loud: Where are the women?

It’s a question that echoes beyond our current times. In the biopharma world, not only are women under-represented in R&D roles (particularly at higher levels), their achievements and talents could also be undermined by stereotypes and norms of leadership styles. The problem is even more dire for women of color.

Jeff Albers, Blueprint CEO

Di­ag­nos­tic champ Roche buys its way in­to the RET ti­tle fight with Eli Lil­ly, pay­ing $775M in cash to Blue­print

When Roche spelled out its original $1 billion deal — $45 million of that upfront — with Blueprint to discover targeted therapies against immunokinases, the biotech partner’s RET program was still preclinical. Four years later, pralsetinib is on the cusp of potential approval and the Swiss pharma giant is putting in much more to get in on the commercial game.

Roche gains rights to co-develop and co-commercialize the drug, with sole marketing responsibility for places outside the US and China (where CStone has staked its claim).

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 85,300+ biopharma pros reading Endpoints daily — and it's free.

Mene Pangalos, AstraZeneca R&D chief (AstraZeneca via YouTube)

A day af­ter Mod­er­na vac­cine re­sults, ru­mors swirl of pend­ing As­traZeneca da­ta

A day after Moderna and the NIH published much-anticipated data from their Phase I Covid-19 vaccine trial, attention is turning to AstraZeneca which, according to a UK report, is expected to publish its own early data tomorrow.

ITV’s Robert Peston reported that AstraZeneca will publish the Phase I data in The Lancet. 

AstraZeneca and Moderna represent the two most ambitious Covid-19 vaccine efforts, having set the quickest timelines for approval (though they were recently joined in that regard by the Pfizer-BioNTech partnership) and some of the loftiest goals in total doses. Yet there is even less known about AstraZeneca’s vaccine’s effect on humans than there was about Moderna’s before yesterday. Although, in a controversial move, Moderna released some statistics from its Phase I in May, AstraZeneca has yet to say anything about what it saw in its Phase I trial — a move consistent with the scientific convention to withhold data until it can be published in a peer-reviewed journal.

Ludwig Hantson, Alexion CEO

Why pay $4B for a steady di­et of dis­ap­point­ment? Porges turns thumbs down on Alex­ion’s M&A strat­e­gy, of­fers some point­ers

When Alexion announced recently that it was paying $1.4 billion to bag Portola and its underperforming Factor Xa inhibitor reversal agent, you could hear the head-scratching going on around virtual Wall Street.

Why was Alexion going down the discount lane for new products? And why something like this? Analysts have been urging Alexion to get serious about M&A for years if it was serious about diversifying the company beyond Soliris and its successor drug. But this wasn’t the kind of heavy-impact deal they were looking for.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 85,300+ biopharma pros reading Endpoints daily — and it's free.

Mil­li­pore­Sig­ma to build new $20 mil­lion, 12,000-square-foot lab in Switzer­land

On the heels of opening a new laboratory in Shanghai last week, MilliporeSigma is continuing its construction push.

The Merck KGgA life science subsidiary announced Wednesday its intentions to build a new $20 million lab in Buchs, Switzerland to support its reference materials business. It’s estimated that the new facility will be completed in December 2021 and open in early 2022 and is expected to be 12,000 square feet.

Stéphane Bancel, Moderna CEO (Steven Ferdman/Getty Images)

‘Plan­ning to vac­ci­nate every­one in the US,’ Mod­er­na out­lines ef­forts to sup­ply their Covid-19 vac­cine as man­u­fac­tur­ing ramps up ahead of PhI­II

Twelve days from the planned start of their Phase III pivotal trial, the executive crew at Moderna has set up the manufacturing base needed to begin production of the first 500,000 doses of their Covid-19 vaccine with plans to feed it into a global supply chain. But the initial batches will likely be ready in the US first, where company CEO Stéphane Bancel plans to be able to vaccinate everyone.

“We have started making commercial product at-risk, and will continue to do so every day and every week of the month,” Bancel told analysts during their morning call on the Phase I data just published in the New England Journal of Medicine.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 85,300+ biopharma pros reading Endpoints daily — and it's free.

Covid-19 roundup: Vac­cine by end of 2020? Ken Fra­zier warns hype do­ing 'grave dis­ser­vice'

When it comes to setting expectations about a Covid-19 vaccine, Ken Frazier does not mince words.

Over a month after first casting doubts on the aggressive 12- to 18-month timeframe championed by the US government and his biopharma peers, the Merck CEO again cautioned against any hype around a quick vaccine approval.

In a wide-ranging interview with Harvard Business School professor Tsedal Neeley that touched other big topics such as race, Frazier emphasized that vaccines take a long time to develop. He would know: Out of the seven new vaccines introduced around the world in the past 25 years, four came from Merck.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 85,300+ biopharma pros reading Endpoints daily — and it's free.