Ep. 35 - ASH Monday, Biden's Picks & Vaccine Conundrums

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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Simone Fishburn:
Simone Fishburn, Editor in Chief
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Steve Usdin:
Steve Usdin, Washington Editor,
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Lauren Martz:
Lauren Martz, I head Translation and Clinical Development Coverage,
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Jeff Cranmer:
It's Ash Monday, Lauren you've been digging into data from the American Society of Hematology (ASH) annual meeting for weeks now, what are the key trends you're seeing?
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Lauren Martz:
A big one that we're seeing is a movement in bispecifics. We've been following the CD19, CD20, BCMA targets for years, and years. And in the preclinical setting we've started to see a lot of new targets but this year at ASH and that some of the other fall conferences we've been seeing different targets that are just starting to emerge with clinical data a great example is Johnson & Johnson and their GPRC5D targeting bispecific. Some other trends are earlier data for CAR-T cells we're seeing the first in line data and a lot of companies are moving into second line.
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Simone Fishburn:
I think that focus on bispecific is really important because we're seeing this now from multiple angles Lauren. We recently did an analysis which we will be running very soon on deal-making in the oncology space and we actually saw that deals in bispecifics was second to small molecules but had jumped ahead of antibody deals on antibodies regular antibodies and on cell therapies. What do you think is the sort of value driver -- why have they become so attractive, and can you also tell us when you say bispecifics you're including BiTEs, and T cell engagers, and regular bispecifics how much of that does it include?
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Lauren Martz:
Sure, so like ASH it's mostly the T cell engagers which are the same thing as BiTEs. So these are biospecifics that target a T cell and activate it in some way and also targeted tumor cell and bring the two cell types together. When you're looking towards solid tumors you're seeing a lot of new constructs that are bispecific antibodies that have different functionalities you know, they might be targeting two checkpoints we're seeing a lot of the same T cell engager concept but instead of using two antibody fragments to do that we're seeing a TCR -- a soluble TCR -- instead for example to open up the target space but it ASH it's mostly still the T cell engagers. In my opinion I think we're seeing so much activity in this space because these are much simpler to manufacture than a CAR-T for example. Which kind of has the same idea you're picking a target on a cancer cell and you're trying to bring T cells, or make T cells that are very specific for that target. And CAR-T cells have been so hard to manufacture and we're still working out how to deliver them, how to get access to them. Bispecific antibodies are maybe easier to produce, and maybe easier especially as we're seeing in this early clinical data maybe it's just easier for initial target validation.
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Simone Fishburn:
So I've got one other question BiTEes was obviously the term from Amgen via its Micromet acquisition other companies have created bispecific T cell engagers that are parallel. What you seem to be saying is that the whole I don't know can we call it as genre or category is growing and it sounds like companies are now going to allow them to get different kinds of targets is that correct?
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Lauren Martz:
I think so, just looking through the ASH abstracts we're seeing so many types of innovation with these bispecific constructs. I saw some examples of people making bispecific prodrugs where they're activated only in the tumor micro-environment so that lets you get to different targets because you don't need to be as specific. I heard from someone that I spoke with that maybe we should be looking forward to seeing bispecific antibody-drug conjugates (ADC). So it's just blowing the target space wide open I think.
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Jeff Cranmer:
So, Lauren, you know we love to pick winners and losers around here just for sport, who are the big winners this morning, any big stock moves that have caught your eye, I'm hearing a lot of chatter about CRISPR data that's just come out?
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Lauren Martz:
The CRISPR and Vertex data in sickle cell and beta thalassemia it looks great in terms of durability, and I think that's what people are looking for. That's just following a trend that we've been seeing with the CTX-101 over the past year or so. I think a big winner this weekend is VelosBio, which recently announced an acquisition by Merck. They have an antibody-drug conjugate (ADC) targeting ROR1 which we haven't seen too much data on. We're starting to see a lot of wins for anybody drug conjugates, and we're starting to see a lot of programs come up in the ROR1 space.
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Simone Fishburn:
That's been a long time coming okay. Cause ADCs people have been sitting around saying for years can you get the toxin right, and this, and that. It is interesting and I think when we look to deals in this space the ADC deals -- six of them had been in the last year or two so there sort of seems to be a sort of surge happening right now. And I would imagine that there's some kind of synergy behind the surge with bispecifics maybe it's a sort of collateral effect of that with ADCs. So yeah I think we're expecting that class too accelerate as well.
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Lauren Martz:
I think that the BCMA race is a great example of that we've seen an ADC come to market first and has pretty good data comparable to a lot of the bispecific I think that's a good proof of concept for that modality.
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Jeff Cranmer:
Excellent, well Lauren did a nice preview piece that's already up on our website -- www.biocentury.com -- and I know you've been busy already today with Paul Bonanos our lead newsman picking through today's data so I look forward to seeing what the two of you right today.
[00:06:08] Now. Word of a benefit from our friends at Kendall Square Orchestra they will be presenting symphony for science an online event with music and words for Next Step supporting people with rare diseases, cancers, and HIV. It'll be December 17th, at 8:00 PM Eastern, registration is at www.symphonyforscience.org.
[00:06:36] Let's turn to Washington. Steve, Joe Biden's team has picked Xavier Becerra, the California AG to lead HHS, and Rochelle Walensky -- she's the Infectious Disease Chief at Mass General and the president elect has picked her to head up CDC, who are these people?
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Steve Usdin:
Well, Xavier Becerra, that pick has really gotten people in Washington scratching their heads ... I talked to people who served in senior positions in the Obama administration, and Clinton administration. And they all say that there are two things that are really needed to succeed as HHS secretary: expertise running a very large organization -- HHS has the second largest budget in government after defense -- and healthcare expertise and he lacks both. He's been an advocate for the Affordable Care Act (ACA), for women's reproductive rights. He's a pugilistic guy who is really gonna be out there punching on behalf of the Biden healthcare agenda but there's a real question about his expertise on the healthcare issues. I think that his nomination makes Biden's picks for FDA, CMS, and NIH far more important because he's not going to be in a position to have the expertise to distinguish between policies that sound great, and are great, and those that sound great but really are really problematic. So I think this is going to be especially important because Biden's gonna find it extraordinarily difficult to get major initiatives through Congress he's going to rely heavily on executive actions and that's going to be particularly true at HHS.
[00:08:14] For CDC Rochelle Walensky, my Twitter stream blew up: everybody thinks that she's fantastic choice. She's as you mentioned, she's the chief of the division of Infectious Diseases at Mass General, she's an expert on HIV AIDS, she's highly respected. She's going to be an enormous contrast to Redfield the current CDC Director who's been a disaster. The only question mark about her I think is her management experience, CDC really went into free fall under Trump and it needs someone who can turn it around. I think everybody's rooting for her and hopes that she's the one who can do it.
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Simone Fishburn:
Steve, so with that I don't know if the word is consternation in Washington over the HHS secretary. Was there a name or names that sort of people where veering towards instead, I know that the Rhode Island governor had been in the running and apparetly took herself out of the running or whatever but some of the reports suggest that was a sort of I don't know if a scramble is the right word. So my question really is this a concern about Becerra that would have parlayed into quite a few of the other candidates or was there some other front runner candidate that people were looking towards?
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Steve Usdin:
Look everybody had their candidates, last week when you, or Jeff asked me who was going to be the HHS secretary I said I wouldn't respond, I wouldn't take the bait because I didn't really know. And look it turns out I'm true, he wasn't on anybody's, Beccera wasn't anybody's list.
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Simone Fishburn:
He was on their list for attorney general.
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Steve Usdin:
Oh yeah, for attorney general, maybe for other positions. Certainly, certainly he was expected to be in the cabinet, but this isn't the position he was expected to be in. And I think it reflects a certain attitude about government that running these big agencies doesn't require subject matter expertise the way that people might view generals in the military that they can swap them around to different places, or maybe even CEOs can go from one corporate domain one kind of company to another which people who know government don't believe is true.
[00:10:12] Yeah, there were other people who were on the list one of them was Sylvia Burwell. Who was acting HHS secretary in the Obama administration right now she's chancellor of American University around the corner from me and it isn't clear whether she would have wanted to give that up. She was certainly high on people's lists; there are other people who were on the list but now it's going to be Becerra.
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Jeff Cranmer:
Now Steve, with Biden's picks in the past few weeks he has tended to announce a whole team whether I think it was defense a couple of weeks ago. Should we expect to see more picks this week, should we expect to see an FDA chief pick this week, or other top posts in healthcare?
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Steve Usdin:
I don't know, I think the fact that he's picked these, he's picked people in groups that suggests that his team is the one who's picking people. I think when you're looking at the one tier down like CMS, and FDA there's an expectation that the HHS secretary would play a role in picking people that they're comfortable with so there may be a delay. There were some other notable healthcare nominations that were announced today also or over the weekend, Vivek Murthy, The Surgeon General; he was Surgeon General in the Obama administration he's coming back he's very highly regarded, Dr. Marcella Nunez-Smith as COVID-19 equity task force chair, Tony Fauci, people have heard of him, as chief medical adviser on COVID-19, Jeff Zients, coordinator of the COVID-19 response, and counselor to the president, and Natalie Quinlin, deputy coordinator of the COVID-19 Response. He has announced a big team for healthcare nobody that I know really knows when he's gonna make the FDA, CMS, and I would expect NIH picks also.
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Jeff Cranmer:
All right, well staying with Washington, late last week trade groups including BIO and PhRMA took their first move to head off the Trump Administration's Most Favored Nation (MFN) scheme to lower drug prices. It's a policy that many in industry fear will quash innovation if it sticks . Steve, what is MFN and how is the industry trying to head it off?
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Steve Usdin:
MFN is a reference pricing system that we applied to Medicare Part B drugs, those are drugs that are administered under a physician supervision mostly biologics. The idea is that the U.S. government would never pay more than the lowest price paid for the same drug by another developed country. As expected BIO, the biotech trade association, and PhMRA which represents big pharmas filed lawsuits they filed in separate courts seeking to overturn or at least delay MFN. The lawsuits go after MFN on several grounds but probably the solidest ground is procedural. The Trump administration used a shortcut called an interim final rule to try to get the MFN policy in place before the inauguration of the Biden administration. It's probably not going to hold up in court at a minimum the courts are most likely to kick it back and say that they're going to have to go through a formal notice and comment rulemaking procedure. That would give the Biden aministration time to decide whether they want to pursue this policy or whether they want to do something else. Biden administration is going to do something on drug pricing but it's far from certain that they're going to want to take this page from the Trump administration's playbook.
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Jeff Cranmer:
All right, thanks for that Steve.
[00:13:43] The vaccine is here... the efficacy at least for the first two seems to be in the bag. Now it's time for the detail questions: first up is the adcom -- advisory committee -- meeting at FDA this week for the BioEnTech, and Pfizer vaccine. And then what, Simone, I know there's a few questions on your mind about the rollout of the vaccines?
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Simone Fishburn:
Right, well I'm actually sitting in the U.K. at the moment we traveled here this weekend. I am in 14 day quarantine which is fine cause it's freezing outside. You know the U.K. is actually on the verge of delivering vaccines and putting them into patients, my parents I hope will be among the early recipients being in the 80 plus class category. And so I've been thinking about a few of the things as I try to explain to them what's going on and what the different vaccines are. And I actually have a whole bunch of questions but you know I picked on three that had come to top of mind. So, you give the vaccine, and then what happens? So one question is there a comprehensive plan to track outcomes, among people who've been administered the vaccine? And that's really important, not only because you have to learn about adverse events and there's always, there's been a long-term. efforts to allow adverse events reporting, but also you need to understand the demographics of uptake and responses, you need to understand how long immunity lasts. There's going to be different vaccines and so you want to understand how these factors vary between the different vaccines, people aren't really going to get a choice is what we're hearing they're going to get what they give and as it were. The U.K. has got the NHS which is a fantastic system for distributing the vaccine I'm not sure how much they're going to be able to use it to track outcomes. Steve told me that Moncef Slaoui from Operation Warp Speed (OWS) has said that FDA and CDC are working to put together a pharmacovigilance system, which is great, although it's going to integrate information from insurance carriers including Medicare and the VA, and a lot of people are going to be getting the vaccine who are actually not part of an insurance system.
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Steve Usdin:
Yeah, I'd break in there. I asked Moncef Slaoui on a press briefing last week what is being done to create a registry to track outcomes and he mentioned the pharmacovigilance steps that CDC, and FDA, and the states are taking, but that falls way short I think of what's needed and it doesn't seem to me to be that complicated at least conceptually. What's needed is that every single person who gets a vaccine should be entered in a registry and there should be an attempt to determine  what their outcomes are solely in terms of COVID-19 did they get it or not? Then we'll get really valuable information about the effectiveness of the vaccines, if there are differences in subpopulations, and so on.
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Simone Fishburn:
I have heard that there's going to be an app there was a story today in The Washington Post, it's actually really more like it's not actually an app it's more like a text alert system. So people are thinking about this there's not a lot of detail and I think one of the reasons there's not a lot of detail is that this has just been so fast. Obviously the priority is to get it, and to get it out there. But I agree with you Steve, I think there needs to be something comprehensive I actually think there needs to be something global we really need to understand these vaccines.
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Steve Usdin:
What that app is they're encouraging people to text them about adverse events. That's not going to track outcomes. And it's also look you're going to get a lot of bogus stuff on there... anti-vaxxers are going to be texting saying that there are adverse events that didn't happen, there are going to be people who just in the course of their lives would have had those events anyway you can have millions of people taking these vaccines the day after they take them just by chance some bad things are going to happen to people.
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Simone Fishburn:
Yeah, it needs to be something more rigorous than that. I think what I'm saying is I think people are starting to think about this but it's far from where it's going to need to be, and this is really the time for real-world data to move center stage. So the other question I was thinking about is this we've heard that the AstraZeneca vaccine is it's either 62% or 90% effective somewhere there or maybe in between either way we'll find out. But the next vaccines are very likely to work but they may well not be 95% effective. And obviously the efficacy works at a population level but it's not exactly binary but it's binary at an individual level as to whether you get it or not. So if you get one of the vaccines that is 70% effective do you find out whether you whether it worked in you or not, and if not what happens can you get one of the other vaccines? What I mean is if you take the vaccine and you then find out you didn't have antibody levels can you get the other vaccine? Or if you get sick, I believe if you get sick you should still be able to get therapies free of charge and there needs to be a plan for this so that people really understand. I think what's going to happen otherwise you're going to have a rush people are going to say, "no I want the 95%, vaccine I don't want to get the 62% one." I think that's something that is not yet clear to me and then my... go ahead Steve.
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Steve Usdin:
I would say that first cause we don't know what the efficacy of the next vaccines is going to be. The other thing I think that's interesting of course is that it's a big world out there it's not just the United States and Europe. I was speaking over the weekend with somebody from the World Bank and what that person was telling me is that in developing countries if there's going to be a choice between a vaccine that's highly effective and is one price point and there's a vaccine that's substantially less effective but is it a much lower price point, they're going to get the cheaper one. And that's what's going to happen, around the world and it does really bring up issues of equity. And I think the lack of planning for getting the whole world vaccinated, which is really what's going to need to happen.
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Simone Fishburn:
And that's absolutely true, and I think that showing that there are plans for equity and the point really is that equity isn't about being given the vaccine it's about being COVID free, right it's about outcomes. That's going to be really important for having people agree to sign up and get the vaccine. And then a third question that sort of occurred to me, and I know others been thinking about this as well is if you've had symptoms, let's even just say if you've had symptomatic COVID, should you also get the vaccine? You're likely to have more immunity than somebody who hasn't had symptomatic COVID. So we haven't been following antibody levels we don't know what happens with them but especially at the beginning when vaccines are scarce, will they triage? Will they ask people if they had it? Will those supplies not go to somebody who already had it? I think that's very important as well. Most of the fears about antibody dependent enhancement have subsided; there were fears early on but it's not been completely put to rest and nobody's really tested one vaccine on top of another, nor have they tested a vaccine on top of somebody who's got high antibody levels. So there's still a lot of unknowns there. And I think again it really comes down to, you know, the downside is that you may have given a scarce resource that could have gone to vulnerable individual, but if the vaccine actually causes harm and people who've got high antibody levels then that's another really big problem. And I think that's just going to be a slew of more questions like this, it's not an inherent criticism. I think that it's incredible that we're in a position to have these vaccines and the distribution has to be engineered and organized as fast as possible -- you can't really wait to get all these answers before you do that. But I think we do have to understand that we are largely flying blind in some of this.
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Steve Usdin:
I think when you say we're going to get all of the answers that's a good segue into really what we haven't mentioned: it's the big event of this week, which is the ad comm for the BioNTech, Pfizer COVID-19 vaccine. We're going to get the briefing documents hopefully tomorrow, maybe even today I think we're going to learn a tremendous amount from them that's going to be really fascinating and important. Because the level of detail that's going to be in the FDA briefing documents is going to be orders of magnitude more than what we've received now which is essentially press releases.
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Simone Fishburn:
Right Steve, and by the end of the month we should start to see data from a couple of the other vaccines as well as J&J's, and we'll start to see the Merck one I think fairly soon some data from it, and more data from AstraZeneca so this is going to be an information rich next couple of months.
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Jeff Cranmer:
Excellent, Steve we'll be following the ad comm this week and of course we'll be following all these pending data drops so keep your eyes on our website www.biocentury.com we have a coronavirus resource center and all of our stories on the pandemic response are in front of our paywall. That's all we have time for this week, thanks for tuning in.
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