Eli whynot

You will definitely want to read this book. These are major changes from earlier eras, during which such reasons would have been viewed as inadequate to justify divorce. Do you think these changes are good or bad for individual Americans and for society as a whole? The All-Or-Nothing Marriage reports that the median age at first marriage surged from 22 and 20 for men and women, respectively in the s to 29 and 28 today. What effects, if any, do you think this change has had on the economy, popular culture, public health, policymaking, or any other aspect of society?

Eli presents evidence that high-investment parenting has surged over the past generation or two. Are these changes good or bad for the institution of marriage—and for society as a whole? In your view, what are those implications?

For example, is there anything that policymakers can or should do to strengthen marriage among poorer, less educated Americans? Do you believe that monogamy is always the best option in marriage or that each couple should make that decision for itself? If you think each couple should decide for itself, under what circumstances do you think monogamy or consensual nonmonogamy is likely to be the better option?

They argue that marriage should instead function as a contract for, say, 5 or 10 years, with the contract renewing if both spouses favor renewal. Given what we now know about marriage, what do you think of the renewable contract idea?

Somers, who has been with WFAN since , went viral in when he "interviewed" the lone baseball writer who did not vote for Mets pitcher Jacob deGrom on his Cy Young ballot. If you missed this exchange when it happened. Twitter follower EddieCarstone reached out yesterday to say there isn't anything more Curb than the scene below. He has a point. You can also follow Jimmy on Twitter and Instagram. Holloway is ready for a dominant UFC comeback this Saturday. With a 1—0 win over Colombia on Thursday, the South American giant continued its dominant qualifying run.

Los Angeles's newest receiver has a new home and a new contract. The Olympian and her girlfriends, all of Asian descent, were waiting for a ride when a car came speeding by, yelling racist slurs at the group. Rich Paul says the three-time All-Star is not ready to play right now.

The former Browns star seems to have sent a lot of texts on Thursday, ranging from Taylor Swift's Red album release to the iconic Wicked Witch of the East debate.

We have, of course, followed progress in the Alzheimer's disease landscape since our last call and are watching closely as CMS's National Coverage Determination process plays out. We're committed to facing the challenges of effectively communicating donanemab's clinical data and value proposition and to ensuring that the diagnostic in patient management ecosystems are adequately well prepared.

Given the current environment, we think it's reasonable to have modest expectations for the scale of patient impact for anti-amyloid therapies available under Accelerated Approval prior to the readout of their definitive Phase 3 data. Assuming positive Phase 3 results, we should be confident in the mid- and long-term opportunity for donanemab if approved. Moving on to Verzenio.

We are delighted to bring this important new treatment option to patients. These data, which reflect additional follow-up since our last public presentation, highlights the robustness of the effect size we're seeing for Verzenio in the adjuvant setting.

These data are not only important for patients, but also to help dispel concerns that the curves would come back together over time. We're clearly observing -- we've clearly observed continued separation of the curves, if not expanding separation.

Since the adjuvant approval two weeks ago, there have been questions regarding why the FDA approval applied only to a subset of the study population.

As previously communicated, overall survival was a secondary outcome measure for the monarchE study and an important component of the FDA's review. While we do not typically publish immature overall survival data, we feel it's valuable to address these important questions about the difference between the enrolled study population and the approved indication. As a result, while the overall survival data remain immature, we do plan to publish the OS data from the additional follow-up analysis with cut off of April 1, in a medical journal in the coming days.

These data will show what we have observed thus far for overall survival trends in the ITT population compared to the approved population. We'll continue to follow patients in the ITT population for more mature overall survival data.

If a positive OS trend emerges in the ITT population, we plan to work with regulators to expand our adjuvant indication. Slide 17 shows select pipeline opportunities as of October 22 and Slide 18 shows potential key events for the year.

There have been several important developments since our last earnings call and I'll cover these by therapeutic area. In oncology, in addition to the exciting news for Verzenio, we continue our investment in pirtobrutinib's Phase 3 program with an additional study starting in chronic lymphocytic leukemia, including fixed duration pirtobrutinib plus venetoclax and rituximab in relapsed or refractory patients.

We plan to start a study in first-line treatment compared to bendamustine plus rituximab before year-end. We prioritized this first line study, rather than the head-to-head study evaluating superiority compared to ibrutinib as we think this first-line study could provide a faster pathway to bring pirtobrutinib to patients in the first-line setting.

We expect the head-to-head ibrutinib CLL study to start in the first half of We plan to provide a regulatory update for pirtobrutinib at our Investor Day in December. Imlunestrant, our oral SERD also moved into Phase 3 with the start of its monotherapy study compared to exemestane or fulvestrant.

We look forward to filing INDs for both programs in and subsequently moving them into the clinic. In diabetes, in addition to the tirzepatide update, we obtained U. We're excited about the opportunity Jardiance has to improve outcomes for patients across type 2 diabetes, heart failure and chronic kidney disease.

We also started Phase 2 studies for our GLP-1 non-peptide agonist in collaboration with Chugai in type 2 diabetes and in obesity, and look forward to sharing some Phase 1 data from this molecule in December. In immunology, we were delighted to have multiple positive Phase 3 readouts for lebrikizumab in atopic dermatitis, and look forward to the readout of the maintenance data from the ADVOCATE-1 and 2 studies in the first half of next year, ahead of global submissions expected by the end of We're pleased with our progress in immunology this year with positive Phase 3 readouts for mirikizumab and lebrikizumab, and look forward to sharing more about our next generation of early phase immunology assets in December.

In neurodegeneration, our anti-tau antibody zagotenemab recently concluded its Phase 2 study in early symptomatic Alzheimer's. Zagotenemab failed to meet the primary endpoint and was unable to modulate tau spread in the brain. The placebo population progressed as expected.

While this negative outcome was disappointing and we're discontinuing development for zagotenemab, we remain committed to tau as a high conviction target in Alzheimer's disease and plan to continue studying tau biology, including inhibition of tau aggregation with a small molecule OGA inhibitor, currently in the clinic. In the pain therapeutic area, in collaboration with Pfizer, we discontinued the global clinical development program for tanezumab following receipt of a Complete Response Letter from the FDA for tanezumab in osteoarthritis pain and a negative opinion adopted by the CHMP.

And finally, the FDA expanded the Emergency Use Authorization for bamlanivimab and etesevimab administered together to include post-exposure prophylaxis in certain individuals for the prevention of SARS-CoV-2 infection. Thanks, Dan. We have seen continued strength in our core business through the first nine months of the year with double-digit volume-driven revenue growth, net of COVID therapies and strong performance across key brands. We're pleased to see sequential and year-over-year operating margin expansion, as well as strong non-GAAP earnings growth.

We have made significant progress developing new medicines and Q3 was another important quarter for our pipeline as we announced the submission of tirzepatide in type 2 diabetes, the initiation of a rolling submission for donanemab in the U. As we move toward the close of , we are confident in our long-term growth prospects. While the past year has seen tremendous advances in our late-stage pipeline, at our Investor Day in December, we look forward to sharing information with you regarding the next generation of assets that we believe will enable us to sustain the flow of innovative medicines to patients and augment our future growth prospects.

We'd like to take questions from as many callers as possible, so we ask that you limit your questions to two per caller. Great, thanks so much for the questions. I guess the first one for me is just on some of the comments. I'm just trying to get my hands around how meaningful of a step-up in opex we should be thinking about supporting these major new launches coming next year.

It's obviously been a challenging launch. Are there learnings here or just changes about how you're thinking about your go-to-market strategy for donanemab? I'm trying get a sense of, again, just as you look at what's happened there, has there been surprises or changes in your thinking on the market? Thanks so much.

Thanks, Chris. We'll go to Anat for the first question on margin expansion and then to Anne on thoughts about the uptake and outlook for donanemab. Great, thanks. So for , we will provide further details and guidance in December, so not too far from now and we'll provide additional material on how we view the year and what investments and pushes and pulls we have going into next year.

As you think about our margin expansion and the goals we've set out and we've communicated in terms of getting to mid-to-highs in terms of margin expansion, we still have a clear line of sight to get there, and that's still our goal. There'll be -- but it's not a linear growth.

So there'll be years that are going to be stronger years or we're going to be making specific targeted investments and as you've seen us do this year with donanemab, when we have strong convictions in a pipeline asset or when we're preparing to launch very promising opportunities and products, we will invest behind them.

So think about this as still growing to mid-to-highs, but not necessarily in a linear fashion, but in line with investments we would need to make. Anne E. Well, as Dan stated and as our competitor has shared, they've experienced, there clearly is work to do to ensure that the diagnostic and the patient ecosystems are prepared for these medicines. And until there is definitive Phase 3 data, we do believe that we should really expect modest use of these medicines.

And so this will be the opportunity to really help patients on a more significant scale. Now some of the opportunities here, certainly pursuing Accelerated Approval is really important, both to provide early access, but also to let us begin addressing some of these infrastructure challenges ahead of the Phase 3 data.

We need to build out the diagnostic ecosystem, particularly PET scans and blood tests. We need to make sure that there is adequate infusion capacity and then very importantly, we need to ensure that there's reimbursements so that the appropriate patients can have access to donanemab. So these are going to be our areas of focus now through our Phase 3 window. We're confident in our ability to address these infrastructure challenges over time. And I would say, by clearing plaque faster and deeper, we believe that, as well as identifying the right patients, we optimize the chances for showing compelling benefits in the Phase 3, which as we've said is what was going to show significant uptake in the class.

We continue to see the same opportunity for donanemab in the mid-to-long-term, once these challenges are addressed and the confirmatory data is available.

Hey guys, good morning and thanks for the questions. I had two on Alzheimer's, probably for Dan. For donanemab, would you expect completion of the rolling submission by the end of this year? And is there a regulatory threshold you need to hit in terms of the safety exposure?

I'm just trying to think of the number of patients that you have to get exposed to? And then for zagotenemab, what are the next steps here? Is it moving to another anti-tau asset altogether, or do you want to optimize monotherapy zagotenemab or maybe even move it forward in combination with donanemab?

Thank you. Thanks, Jeff, for two good questions. The first is just on the timing of the completion of the donanemab rolling submission.

I think you can assume we chose our words carefully here in the call prepared remarks, on the timing. You're sort of driving at like what's the regulatory hurdle with respect to safety exposures. You're right, that's the key gating factor on timing. You've heard we've enrolled a lot of patients in the clinical trials, including patients in a safety addendum. So we're extremely confident we'll reach that safety exposure hurdle.

I guess, looking forward, there's probably two risks or question marks. One is just around the timing of exactly when do databases get locked and data get cleaned and submitted to the FDA. So that's why we're a little vague on timing here. I think the second one, of course, that we don't know and won't know until all that data is in, is what does the safety data actually show.

And so the assumption here of course is that they continue to be consistent with what we've seen in Phase 2. So if those things work out then I think that will be the opportunity to talk a little more specifically about the data.

With respect to zagotenemab, look, I think we have here a very potent anti-tau antibody designed against what we believe is an important species of aggregated tau delivered at relatively high doses for any monoclonal antibody and we were unable to slow the spread of tau progression in the brain. So at present, I don't see a path forward for this antibody and I would be reluctant to invest in really any anti-tau antibody, given what we've seen here.

Tau is still a great target. It's just hard to hit it with a monoclonal antibody I think, given that most of the tau that we care about is inside of cells. Hi, thanks for taking my questions here. So my first question is, how are you preparing for the launch of donanemab and tirzepatide next year and how should we think about the costs associated with that launch?

We'll go to Anat for the question on just the launch prep and the overall costs for both tirzepatide and donanemab, how we think about that going into next year.

So as we're preparing to launch both these medicines, obviously, one is in an area where we have significant commercial footprint, manufacturing and scale-up capabilities and the other one is an area we're currently building. So we're investing in advancing both of these efforts toward preparing for a potential launch of tirzepatide mid next year and then regulatory decision on donanemab at the second half of next year.

Those will be factored into the guidance that we will provide on December 15 as we go into next year, but rest assured, we're building the commercial footprint that we need to launch these effectively and leveraging the existing footprint we have as well. Well, it's a good question that you've asked and I do think there's a number of things that are a challenge here. I think as you look at donanemab, what's incredibly important is that we had a positive Phase 2 study that cleanly met its primary endpoint showing cognitive benefits for donanemab.

As well, we were able to share that we had limited duration dosing to plaque clearance and so we believe that this is going to be important for the decisions that physicians and payers make. So I believe the donanemab data is incredibly strong. And then as I said, following quickly the Phase 3 confirmatory data, which I think is important, and all of this published in the New England Journal of Medicine.

So as we're talking to thought leaders and physicians, I do believe that they see the strength of the data that we brought forward donanemab. And I think that's been a challenge that they've had with some of the competitive space.

So I do think that data is one thing on their minds. I think as well the NCD is playing a role. Obviously that will be resolved before we launch and we'll be ready for any of the potential outcomes there and have been working closely with them along the way to make sure that they understand the donanemab data, particularly the rapid clearing of plaques as well as the limited duration dosing that offers, we think, benefit to them as well. So it's been a good conversation with them so far.

We really look forward to seeing what they have to say -- CMS has to say in January and then launching with the strong data sets, as Dan said, in the second half of next year.

Hi, thank you. So two questions. First, it's commonly said that this upcoming decision will pertain to the whole ABA class. I struggle to see how that can realistically be the case because that decision will be made on only one company's mixed Phase 3 data and there is still other really important informative Phase 3 data sets that are going to come.

So wouldn't the NCD, whatever it is initially, potentially be revised later as CMS has more information from these additional trials? And then second, if this is indeed a decision that pertains to the whole class, and presumably Lilly has a view on what will happen in January, so do you expect CMS will say that ADUHELM and the class more broadly should be covered in a way that will be commercially meaningful?

One can envision that there could be lots of restrictions that might impact or limit the commercial market opportunity.

Well, thanks for the good questions on the process with the NCD. Now, as I said, we are actively participating in the process, including, we provided oral comments in July and additional written comments in August. And we, and I'm sure others as well, have been meeting with CMS throughout the process to share our specific data and ensure that the differences in these medicines are understood. And so we've asked them really to evaluate each drug based on their own data. And this is, I think, as I said, particularly important considering that there are some differences between these.

We shared the data later in the year subsequent to the original readout that the degree of donanemab plaque clearance relates to clinical benefit, which I know is very important to CMS in this decision, as well as the limited duration dosing.

So we really look forward to see what they have to say in January and what that readout will look like. We do acknowledge there's a lot of skepticism in the national discussion. And so we do really hope and where it will continue to influence, that we think each drug should be evaluated by CMS, by payers, and prescribers on their own data. It is possible that NCD -- the NCD will narrow for the patients most likely to benefit, that's a possibility out of this, but that's really aligned with the goals that we've had in our clinical trial designs, which has long been to use the diagnostic tools to make sure that the right patients are getting treatment.

So, we'll look forward to the readout in January, we'll continue to stay very engaged in this. And yes, I believe, as additional data comes out, our data and others in the class, that this will continue to influence the process. The noise coming out of Washington suggests that BIIB's [Phonetic] battle, some of the components of that are gaining traction in some of the more worrying components, so the price negotiations seems to be more and more limited.

I just wonder if you could share any thoughts on what you think, just take the BIIBs proposal on after pocket caps, could mean to Lilly and the former in terms of increased volume without catastrophic coverage changes. And then second, could you comment on whether you're seeing neutralization of donanemab by the anti-body drug antibodies that you see with prolonged usage and is this one of the factors which is contributing to the finite treatment duration or is neutralization simply not a concern here?

Yeah, thanks, Andrew, for the question. Obviously, there's a lot of talking and discussing going on in Washington about how to make medicines more affordable. I think we've been pretty consistent in our view that both as Lilly and I can -- I think I can speak for the industry here, we are for progress.

We are not for the status quo. And the centerpiece of almost every part of legislation being discussed, which is I think good news for seniors, is some reform to the Part D benefit. That is certainly highlighted in Representative Peter's bill. It's in H. It was in the Grassley-Wyden effort. It's, I'm sure, in the Senate Finance effort now. And I think that's good news. The contours of that are all kind of different but the general idea is that industry would pay additional cost into the system that, that would reduce monthly out-of-pocket costs, both below and above the catastrophic phase cap -- catastrophic cost as well as eliminate the donut hole.

I think we're basically for all those things, and we think that's a good set of initiatives. Where the debate sort of kicks in is around how to pay for that or whether pay force from the industry should go to other healthcare priorities. And, of course, we have clear positions on that. One piece of Peter's bill we don't like is the retroactive CPI cap. I think that's punitive and unfair.

It also is disproportionate on some types of medicines versus others. So I think the industry is aligned. We don't care for that, although in general, the idea of a CPI regulator on forward price increases is something people have gotten used to talking about.

And then the thing we do put our foot down and firmly oppose and why we're so against H. Isn't drug pricing a big enough problem?

Why don't we take the money out of the pharmaceutical industry and give it to patients who want to buy our medicines? And that's a position we've had for a long time. I think it's been a busy week and into next week, probably, negotiating out this package. But we're hopeful that some of these messages are resonating and we could land with a Part D reform and modest impact on the industry so we can keep innovating for the future.

Thanks, Andrew, for the question on anti-drug antibodies or ADAs. We do see ADAs with donanemab, they arise pretty early in treatment. There is no connection, though, with ADA's in our decision on fixed duration dosing.

The reason for that is because the doses that we're using are so much higher than the level of anti-drug antibodies that we don't see an effect in our clinical trials at these doses of the ADA's on PK or importantly on PD, which is the plaque clearance effect of donanemab. So no connection there. Thanks for the question. So, maybe first on the performance of Verzenio in the quarter and then your conviction that this market can accelerate moving forward now with the Ki approval.

We're hearing good things from physicians, but it just doesn't seem to be reflected in the opportunity that I think we all see ahead for Verzenio.