Ep. 25 - Alzheimer Milestones & Vaccine Politics

Transcript
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Jeff Cranmer:
Welcome to BioCentury this Week, I'm Jeff Cranmer, Executive Editor of BioCentury and I'm joined by
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Selina Koch:
Selina Kotch, Executive Editor
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Steve Usdin:
Steve Usdin, Washington Editor.
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Jeff Cranmer:
Selina it's very timely to have you on as you're the one that's been following all of the Alzheimer's news for us over the past couple of years. Today we learned that FDA will host an advisory committee meeting November 6th, to discuss Aducunamab from Biogen for Alzheimer's . Biogen faces the March 7th decision date for the therapy, which offers the possibility of being the first disease modifying drug for Alzheimer's, it's by no means a slam dunk.
[00:00:44] Selina, what are your thoughts?
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Selina Koch:
Investors are clearly watching it carefully. Every little sign of news seems to change Biogen's market cap by billions. This morning it's added $2 billion on the news that it could get to a decision sooner than expected, that having the ad comm in early in November could translate into an earlier decision than the expected March 7th. Back in April and May said that they were going to be delayed in their submission of their BLA, they lost I think $5 billion in market cap...
[00:01:15] So everybody's watching it really closely. It's a huge indication, I think in the United States alone there's something like 6 million patients, so the market is huge. But even if it got approved it's not that a couple of extra months, it's not going to translate into $2 billion in revenue. It could certainly take some time for sales to ramp up given that it's an infused drug, and a lot of these places where patients are treated don't have infusion centers. This remains to be seen, but it may require a PET positive PET scan for amyloid. That's currently not covered by Medicare this is almost entirely a Medicare population. I think the stock move is more like, people just looking for any indication of whether this could be a positive result, right?
[00:01:54] And that's the thing that's...
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Steve Usdin:
The thing that I wonder is even if it is a positive result, even if they do get approved, is it really even certain that huge market will jump right in and start lining up to get quarterly infusions?
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Selina Koch:
I think that there are market access issues. Like I was saying before, not everybody's going to have access to an infusion center; they might have to drive. Not everybody is going to have the means to get the PET scan to see if they have amyloid, to see if they qualify if should that be a criteria. There aren't good treatments for this disease. I think patients will certainly want to try it if they can, if you just look at the alternatives. But it's very uncertain they had two Phase III trials, one was a failure utterly, the other one produced these positive results and everybody is scratching their head what does that mean. The company has their story about how a protocol amendment that differentially affected the trials meant that more patients got the high dose and it's really this high dose that's the thing that patients need, we'll see if FDA agrees.
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Jeff Cranmer:
Going into the year it was certainly the biggest milestone on buysiders radar, and then a little global pandemic shook some things up and now we're obviously very closely watching the vaccine race for COVID-19. We had another big milestone last week when we got the first Phase II data for an anti-tau monoclonal antibody. When AC Immune and Genentech said that their mAb missed the primary, and two secondary endpoints in their Phase II trial to treat a very early stage Alzheimer's.
[00:03:32] What does this mean for Alzheimer's drug developments, Selina?
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Selina Koch:
Yeah I think it means -- at least you can say tao is now starting to look a little more like amyloid companies. There's two major pathologies, that define Alzheimer's. One is amyloid aggregation, the others tau aggregation, and there's been so much trouble with amyloid. Now you see all the major players who are in amyloid are now lining up behind tau as the next big target. And the storyline has been... amyloid is this initial insult, but this disease takes decades to develop. You may not be able to treat early enough to get a meaningful improvement for patients with amyloid. But tao, tao correlates spatially in the brain, and temporarily much better with symptom onset. Therefore tau's going to be the thing that really breaks through.
[00:04:22] We've now seen in the Alzheimer's setting of tao antibody failing to improve cognition, or slow down the decay of cognition. And in a different disease to other anti-tao mAb's progressive supranuclear palsy had failed before. One is from Biogen, one is from AbbVie they're both still in testing in the Alzheimer's indication. But there's at least 9 therapies that have made it to the clinic against tao and many more in preclinical pipelines. So what we could be looking at is parallels to amyloid in terms of the number of companies who want to give it a go. The difficulty of finding the right disease stage, patient population, so on and so forth, that sets us up for years and years of failed trials where we don't quite know why they failed. I should say the biomarker data yet from ACM unit Roche's compound are not available. So we don't know, did it move the biomarkers, did it actually test its hypothesis that remains to be seen.
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Jeff Cranmer:
When do we expect to see those biomarkers?
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Selina Koch:
We don't know for sure. Genentech just said that they're gonna report on it at an upcoming medical conference, so that could be later on this year I think there's a couple of possibilities in November.
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Jeff Cranmer:
That'll be a, certainly something that we'll be watching for.
[00:05:38] Well let's shift gears to the other big thing we're watching for. Steve, you had a chance to sit down with Moncef Slaoui last week he of course is the chief scientific advisor to Operation Warp Speed, and one of the most respected and biggest names in vaccine development. For years he headed up GSK's vaccines division. Recently he's come under fire from Elizabeth Warren whose accused him of a lack of transparency perhaps. Steve, what did you learn in your conversation with Moncef?
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Steve Usdin:
You know, these days we don't actually sit down with people. I talked to him over zoom like everybody else these days...
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Jeff Cranmer:
Sorry, I'm an old fuddy-duddy, I missed the whole days Steve.
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Steve Usdin:
So do I, I would have liked to sit down with them.
[00:06:21] Anyway, as you say, he's the co-leader of Operation Warp Speed and to me actually the most important thing that he told me was that he expects two vaccines and two drugs that reduce mortality to be authorized by the end of the year, or at the latest that it could slip until early 20, 21. That to me is the most important thing. He's the person who I think is the best placed, probably in the entire world to know what the status of the vaccine and drug development is, and that was his opinion. He also addressed senator Warren's accusations, and she didn't say too delicately. She didn't accuse him of a lack of transparency she flat out said he's corrupt and he's motivated by greed, and he was pissed off by that. I thought it was important to hear from him and to give them a chance basically to defend his integrity, and the integrity of the vaccine development process. And I would encourage anybody who is interested in it read the interview that I did. We've got the interview, the Q & A verbatim in BioCentury, and it's in front of the paywall and they can form their own opinion.
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Jeff Cranmer:
I saw his statement that he issued it's all over Twitter, he looks like he's getting ready for a boxing match going into that.
[00:07:28] So Steve before that all blew up late in the week, earlier in the week we saw top officials from NIH, FDA, and CDC head to the Hill to discuss countermeasures development and they really seem to go out there to set expectations for countermeasures development, and build confidence in the vaccines that are being developed.
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Steve Usdin:
Really it was an amazing spectacle, it was on the 23rd. FDA commissioner, Stephen Hahn, CDC director, Robert Redfield, and Tony Fauci spent hours on the Hill trying to convince a Senate committee, and the American people, and maybe themselves that any decisions that are made about COVID vaccines will be made by non-political career staff based on science, and the law.
[00:08:13] Then a few hours later President Trump said he's the one who be making final decisions about FDA vaccine guidance, and he accused FDA staff of intentionally delaying vaccine authorization to help Joe Biden win the election. It was really, it was a gut punch to the agency staff they've been working 24 seven for months on this. White House chief of staff Mark Meadows went on the talk shows on Sunday said that he'd spoken with Hanh about the guidance and his concerns that FDA was unnecessarily delaying vaccine authorization decisions. The thing is that guidance doesn't actually create any new obligations, a guidance can't create it, legal obligation. All it does, is it makes public the criteria that FDA has already been communicating to companies behind closed doors.
[00:08:59] I think the kind of the bottom line of the whole thing is the incident further damages FDA's credibility. And it's going to make more Americans hesitant to take a vaccine once one is authorized. Even if the White House suppresses the guidance, it's not going to speed the authorization. In fact it's more likely to slow it because there'll be less clarity about what FDA's criteria are, and there'll be more, more reluctance by the FDA to be acting quickly, because they know that it's important that anything that they do isn't tainted by political interference and isn't seen to be tainted by political interference.
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Jeff Cranmer:
It seems absurd to talk about this being a process that's slowed down. What's the fastest a vaccines ever been approved before?
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Steve Usdin:
I think it was about 13 years. Now we're looking at something that's going to be likely to be authorized in less than a year after they started. It's happening at a phenomenal speed, and to be honest I think it's amazing that the administration would choose to attack FDA, and the integrity of the FDA, and complained that this hasn't been happening fast enough. Because this is something that actually that the administration should be taking pride in they should be boasting about this. It really has happened this quickly exactly because of Operation Warp Speed. That's one of the things I asked Moncef Slaoui, I said what would have happened in the absence of Operational Warp Speed? And he went through a couple of the clinical trials that are in Phase III now, and he said one of them would have been in Phase I now in the absence of Warp Speed. The other one, the Phase I trial wouldn't have even started yet.
[00:10:31] And then when it comes to manufacturing, they're expecting to have hundreds of millions of doses of it available by the middle of next year. And he basically said that they wouldn't have been any, or there's a good chance there wouldn't have been any available in the absence of Operation Warp Speed and the U.S. government stepping in and investing in manufacturing and paying for manufacturing at risk.
[00:10:51] It's a phenomenal story, and instead of telling that to the American public, the president and the White House has chosen to spin a narrative of a deep state conspiracy by FDA officials to, to slow down the process.
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Jeff Cranmer:
Yeah, it really is absurd. It's easily been one of the biggest successes of this administration and why not celebrate that success.
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Steve Usdin:
The other thing that's interesting, it's not a political event and it shouldn't be. One of the things that Moncef Slaoui said to me, he said "look, I'm a registered Democrat", that's what he said, and that he's not there to try to bolster the president's chances of being reelected, or to take any kind of political stance on this. He's trying to get this thing done as quickly as possible. I think again, you know anybody can read what he said come to their own decisions about whether he's the right person for the job, whether the allegations of conflict of interest are justified or not. But the fact is, he is the one who's in the job and the results are going to speak for themselves.
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Jeff Cranmer:
Yep, it certainly would be a nice note to end the year on if we had a COVID vaccine, and Alzheimer's therapy out there, fingers crossed.
[00:11:59] That's all we have time for this week. Thanks Selena, and Steve for joining me... Before we go, I just wanted to let you know about our 7th Annual BioCentury-Bay Helix China Healthcare Summit. Registrations is now open for this digital event, which will run from November 9th, to 13th. It will include strategic panels, one-on-one virtual meetings, company presentations, two conference reports from our partners at McKinsey. Register today and you'll get immediate access to our pre-event program, including BioCentury Business Intelligence on China Biotech, scene setter presentations on China financings and deals. We'll also have 4 pre-event webinars starting next month.
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