The Regeneron Pharmaceuticals Q2 2019 Earnings Conference Call. My name is John, and I'll be your operator for today's call. At this time, all participants are in a listen only mode. Later, we will conduct a question and Please note the conference is being recorded. And I will now turn the call over to Justin Holco.
Thank you, John. Good morning, good afternoon and good evening to everyone listening around the world. Thank you for your interest in Regeneron Pharmaceuticals, and welcome to the second quarter 2019 conference call. An archive of this webcast will be available on our website. Joining me today are Doctor.
Leonard Schleifer, Founder, President and Chief Executive Officer Doctor. Georgi Ancopolis, Founding Scientist, President and Chief Scientific Officer Marion McCord, Senior Vice President and Head of Commercial and Bob Landry, Executive Vice President And Chief Financial Officer. After our prepared remarks, we will open the call for Q on the call today include forward looking statements about Regeneron. Such statements may include, but are not limited to those related to Regeneron, its products and businesses, financial forecast and guidance, development programs and related anticipated milestones, collaborations, finances, regulatory matters, payer coverage and reimbursement issues, intellectual property and pending litigation and competition. Each forward looking statement is subject to risk and uncertainties that could cause actual results and events to differ materially from those projected in that statement.
A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities And Exchange Commission, including its Form 10 Q for the quarterly period ended June 30, 2019, which has been filed with the SEC today. Regeneron does not undertake any obligation to update publicly any forward looking statements whether as a result of new discussed on today's call. Information regarding our use of non GAAP financial measures and a reconciliation of those measures to GAAP is available in our financial results press release, which can be accessed on our website. Once our call concludes, Bob Landry and the IR team will be available to answer further questions. With that, let me turn the call over to our President and Chief Executive Officer, Doctor.
Len Schleifer.
Thank you, Justin. Before we begin, I'd like to extend a warm welcome to Justin who joined us early this summer after completing a 19 year training program at Merck and has immediately hit the ground running here at Regeneron. We're thrilled to have him as part of the team and we work hard to make his first quarter a straightforward one. Thanks to everyone for joining the call and turning to our business. We had a great quarter actually marked by top and bottom line growth as well as important advances across our innovative R and D engine.
Sales of Regeneron products, including those recorded by our partners, grew 32% compared to the second quarter of 2018. EYLEA global net sales grew 13 percent to $1,900,000,000, including U. S. EYLEA net sales growth of 17% to one $160,000,000. The diabetic retinopathy approval in May continues to build upon Eylea's leadership position in treating retinal diseases including wet age related macular degeneration, diabetic macular edema, and retinal vein occlusion.
We are also pleased to announce that our antibody collaboration with Sanofi achieved profitability this quarter. We expect profits to continue to increase, driven by growth in Dupixent as well as disciplined cost management across the collaboration to stem losses from Praluent by better aligning investments with revenues. Dupixent is fulfilling its potential to improve the lives of patients by transforming the treatment of a variety of type 2 allergic diseases. Global net sales are now annualizing at more than $2,000,000,000. Patient initiations in the U.
S. Are growing and many ex U. S. Launches are just beginning. Building on this commercial momentum, in June, we received FDA approval for Dupixent in chronic rhinosinusitis with nasal polyposis.
In the EU, Dupixent was approved in May for severe asthma in adults and adolescents, and as we announced this morning, was just approved for atopic dermatitis in adolescent patients. We also announced today the strong positive results of our phase 3 study in children aged 6 to 11 with severe atopic dermatitis. We are enthusiastic about the current and future prospects of Dupixent as a treatment directed at the underlying cause of allergic diseases. Additionally, we are making significant progress towards building a leading presence in immuno oncology. The U.
S. And EU approvals for Libtayo and advanced cutaneous squamous cell cautionoma, adjust the beginning. Our clinical efforts, which now include multiple different immuno oncology programs, are studying a wide variety of potential drug candidates in several difficult to treat cancers, including non small cell lung cancer, basal cell carcinoma, cervical cancer, ovarian cancer, non Hodgkin's lymphoma, multiple myeloma, and prostate cancer. Beyond oncology, we continue to move novel programs forward throughout early and late stage development. George will speak to a few of these programs and additional data readouts are expected later this year.
We've made critical advances that have led both to top line and bottom line growth, but we recognize that these advances may be overshadowed by the current policy debates on affordability and accessibility of innovative medicines. We continue to work with policy makers to develop responsible solutions that address affordability and accessibility, while preserving incentives to develop transformative treatments of the future. Now, I'll turn the call over to George.
Thanks, Len. Let me begin with Eylea, the market leader based on its ability to improve vision across multiple retinal diseases. Along with its safety profile established by over 25,000,000 injections. In addition to Eylea's indication for the treatment of wet AMD, For macular edema following retinal vein occlusion and for diabetic macular edema or DME, the FDA label for Eylea was bandoned in May to include diabetic retinopathy without centrally involved DME based on the Panorama study. In this diabetic retinopathy setting, our updated label shows that Eylea demonstrated an 85% to 100% reduction in the incidence of vision threatening complications.
In addition, we are waiting FDA action on our resubmit filing for the Eylea pre filled syringe. In terms of our future innovation and retinal disease, we are planning to initiate clinical programs with a higher dose formulation of the Plibercept in wet AMD and in DME by the end of 2019. These studies will test a higher dose of the Flubicel in 12 16 week regimens compared to the recommended Eylea regimen of 2 milligrams every 8 weeks. Beyond the fluvacep, we are continuing preclinical development of a new VEGF blocker, gene therapy and other novel approaches, including with our new collaborators at Alnylam. I'd like to now turn to Dupixent our breakthrough therapy that is already benefiting many patients in a wide variety of atopic and or allergic diseases.
As Len mentioned, we achieved several important regulatory milestones. Beyond the highlighted approvals, an opinion by the European Committee for dysmal products for human use or CHMP for chronic rhinosinusitis with nasal polyposis is anticipated by the end of 2019. And just this morning, we announced positive results of the Phase III trial in severe pediatric atopic dermatitis patients aged 6 to 11 years which we intend to submit to regulators in the coming months. I would like to remind you of the tremendous unmet need in this population On average, the children in our study had nearly 60% of their body covered with lesions and had suffered from this disease for most of their lives. Leaving the children and their families devastated and without much hope.
Not only did Dupixent dramatically reduce skin involvement as measured by EZ score, by an average of about and their families. The study also confirmed Dupixent's established safety profile and once again, numerically reduced skin infections. We are deeply committed to bringing Dupixent patients suffering from a range of type 2 inflammatory diseases driven by the interleukin-four and interleukin-thirteen pathways. With that, go in mind, we are active enrolling patients in Phase III studies in eosinophilic esophagitis and chronic obstructive pulmonary disease or COPD. As a reminder, we're also exploring the effectiveness of Dupixent allergy desensitization settings, such as for grass and peanut allergy.
While allergy immunotherapy can be effective in the long term, many patients can't complete the prolonged time course required for success because of allergic reactions, which can be severe. We recently completed a small phase 2a trial with about 25 patients for treatment arm, testing whether Dupixent could improve the safety, tolerability and efficacy. Of subcutaneous immunotherapy or SKIT therapy for grass allergy. The preliminary results of this study showed that about 30 patients' discontinued therapy in the SCID group, mostly due to clinically meaningful allergic reactions. Compared to only a single patient who discontinued skip when combined with Dupixent and not due to an allergic reaction.
And in the primary efficacy analysis, there was no difference in terms of reduction of the allergic symptoms with SCIT or in the combination. Thus, we are encouraged by the potential of Dupixent to increase the tolerability of SKID therapy, and we're looking forward to presenting the results at a future medical meeting. Earlier this quarter, we reported that Regeneron 3500, our interleukin-thirty three antibody met primary and secondary endpoints in a proof of concept study in moderate to severe ASM patients, showing that Regeneron 3500 may provide an alternative therapeutic option for asthma. Although, the Regeneron 3500 results were numerically lower than those for the Dupixent Calibrator on. In addition, the combination of REGENON 3500 in Dupixent did not demonstrate increased benefit compared to Dupixent monotherapy in this trial.
All of the study was not powered for this comparison. In addition, within next 12 months, we're expecting interim results from the Phase 2 Regeneron 3500 studies in COPD and in atopic dermatitis. I will now shift gears to our immunotherapy efforts to treat cancer. Starting with Libtayo. Last month, our PD-one antibody was approved in the EU for adults with metastatic or locally advanced cutaneous Squamous cell carcinoma, who are not candidates for curative surgery or curative radiation, making Libtayo the first and only approved medicine of any kind for patients with advanced CSCC in the U S.
And Europe. With the goal of making Libta available for a broader population of CSCC patients, we started a Phase III study in adjuvant CSCC. In addition to an ongoing investigator initiated study, Our study in the neoadjuvant setting is scheduled to start in the fourth quarter. Additionally, our pivotal study of Libtayone Basaloprostenome The most common skin cancer is expected to read out in the first half of next year. Moving on to non small cell lung cancer.
We are pleased by the enrollment for our Libtayo monotherapy phase 3 trial in high PD L1 expressers. We have commenced enrollment in part 2 of our other phase 3 lung cancer study which will compare Libtayo plus chemotherapy to chemotherapy alone, regardless of PD L1 status or histology. Beyond checkpoint inhibition, our investigational bispecific antibody franchise consists of 2 broad categories based on the T cell receptor to which to bispecific spine. CD3 molecule or the CD28 costimulatory bispecifics. In total, we now have 4 bispecifics under clinical investigation.
Our CD20xCD3, BCMAxCD3, MUC16xCD3, and notably, the newest addition of our first co stimulatory bispecific PSMA by CD28. Additional candidates are expected to enter the clinic in the upcoming months and years. In June, we presented updated efficacy and safety data for REGN1979, our CD20xCD3 bispecific. Regeneron's 1979 continues to show high response rates in heavily pretreated non Hodgkin lymphoma patients. In particular, we observed complete responses in 4 out of 7 diffuse large B cell lymphoma or DLBCL patients.
Treated with Regeneron 1979 doses 80 milligrams or higher. Notably, 4 of these had failed prior CAR T therapy and 2 of which achieved complete responses. Regeneron 1979 has demonstrated manageable tolerability with no discontinuations due to cytokine release syndrome or neurotoxicity to date. Recruitment for our potentially Pivotal phase 2 trial for a general in 1979 is now ongoing. The multi arm study will enroll several disease specific cohorts of relapsed refractory non Hodgkin's lymphoma patients, including follicular lymphoma, DLBCL and other non Hodgkin's lymphoma subtext.
Our 2 other CD3 bispecific antibodies, MUC16 by CD3 for platinum resistant ovarian cancer, and BCMA by CD3 for relapsed refractory multiple myeloma are in clinical studies that are actively enrolling patients. We plan to present preliminary BCMA by CD3 data by the end of 2019. Finally, recruitment is ongoing for the First, co stimulatory candidate, Regeneron 5678, which binds prostate specific membrane antigen or PSMA on tumor cells, as well as the CD28 costimulatory molecule on T cells. Based on preclinical evidence, we are hoping to see synergy of our co stems with Libtayo in disease settings such as prostate cancer that have proven resistant to immunotherapy alone. If successful, this innovative approach could open up the possibility of immunotherapy to a large number of patients who do not currently have this option.
In addition, we expect a number of updates related to other programs emerging for our own pipeline. By the end of 2019, We are planning to present our C5 antibody data in patients with paroxysmal Nocturnal and hemoglobinuria or PNH. By the end of this year, we also expect readout of our ANGPTL3 antibody Phase III study in homozygous familial hypercholesterolemia. As well as a readout of our active in any antibody pivotal study in the rare disease, fibrodysplasia, ossificans, Progressive, or FOP. Phase 3 studies at Fasinumab, our advanced candidate for osteoarthritis pain, are now fully enrolled and data are expected during 2020.
Finally, we just celebrated the 5th anniversary Exome data with detailed medical records. We continue to be excited about our ongoing effort here, including our work to sequence the UK Biobank database in collaboration with consortium of leading biopharma partners. Mining of the Regeneron Genetics Center database has already discovered and or validated a number of genetic drug targets across several human diseases, which are positively impacting our current development efforts. With that, I'll now turn the call over to Marion.
Thank you, George. In the 2nd quarter, we executed well across our portfolio of existing lines of business and recent launches, Starting with EYLEA, global met product sales grew 13% year over year to 1,900,000,000. In the U. S, net product sales grew 17% year over year and 8% quarter over quarter to 1.16000000000 EYLEA growth is driven by share gain and market expansion underpinned by the Asian population and increase in diabetes prevalence. And the branded U.
S. Anti VEGF market, our share increased to 71% of net product sales. In the quarter, a temporary shortage of Avastin in select geographies modestly impacted Eylea net sales. EYLEA continues to help patients with diabetic eye disease, and this represents an important growth opportunity for the brand. In mid May, the FDA approved IEA to treat all stages of diabetic retinopathy and our launch commenced immediately.
For this indication, IDEA is the only anti VEGF approved with 2 dosing options, allowing doctors to customize treatment to their patients' needs. Our comprehensive plans to develop Eylea's position in the diabetic retinopathy market are underway. We began educating both physicians and patients upon approval, encouraging early intervention for appropriate patients and ensuring EYLEA is the first line anti VEGF treatment. It's early days in the launch, but we're pleased with feedback from retina specialists, and we're seeing positive early interest in take among major practices. We are investing in Eylea's promotional platforms to advance our market leading position across all indications including wet AMD, DME and in diabetic retinopathy.
Our expanded and realigned sales force has the messaging both EYLEA's clinical and real world experience are well underway. Digital outcomes and safety remain the standards by which therapies are compared, and Eylea's rapid and sustained outcomes in improving and protecting vision are unsurpassed. We're committed to further strengthening our leadership position for Eylea through continued innovation, including in dose and delivery. Hending FDA approval, the Aaliyah prefilled syringe will be launched in 2019. I'd now like to turn to Libtayo.
The launch in cutaneous squamous cell carcinoma or CSCC continues to gain momentum and in the U. S. Net product sales were $41,000,000 for the quarter, Brand awareness within the medical community is growing, demonstrated by the breadth of prescribers at major cancer centers and community practices around the country. Since launch, we made further progress in establishing Libtayo as the standard of care in advanced CSCC across all lines of therapy. Market research indicates more than three times as many CSCC patients are now receiving an anti PD-one or PD L1 treatment compared to before Libtayo's approval.
We believe Libtayo is poised for continued growth. We have broad payer access, and a 2A recommendation from the National Comprehensive Cancer Network, Libtayo is the only checkpoint inhibitor to have this designation in CSCC. Additionally, ex U. S. Launches in CSCC are underway, and we look forward to data that could expand the potential of our dermatologic oncology portfolio into earlier stages of CSCC and beyond.
Moving to Praluent in the second quarter, global net sales were $74,000,000. In the highly competitive U. S. Market, we remain focused on patient affordability and physician ease of prescribing, we are working closely with our collaborator, Sanofi, to greatly improve brand profitability. Turning to Kevzara.
In the 2nd quarter, global net sales were $59,000,000. In the U. S, Kevzara continues to make headway in the IL-six subcutaneous class with an estimated 47% share share of total scripts or TRx. Now for Dupixent, which is transforming the lives of patients suffering from The Type 2 inflammatory disease is atopic dermatitis, asthma, and now chronic rhinosinusitis with nasal polyps. Global net product sales in the 2nd quarter were $557,000,000 and the U.
S. Net product sales reached $455,000,000, representing 151 percent year over year growth. Total prescriptions or TRx in the U. S. Grew approximately 30% compared to the first quarter.
This was driven by continued growth in approved indications, adult atopic dermatitis and asthma as well as the launch in atopic dermatitis for adolescents, weekly new to brand prescription or NBRx for the second quarter averaged approximately 1200 patients per week, up from 950 in the prior quarter. This momentum is further evidence of the positive impact of our commercialization strategy and execution across all approved indications. As we mentioned last quarter, prescribing continues to grow in adult atopic dermatitis as more moderate patients are just prescribed Dupixent. And more health care professionals gain brand experience. Proved for adolescents, many of whom remain uncontrolled using topical therapies.
Market reaction has been extremely positive. Chartered physicians are prescribing and excited about the results they're seeing. There is significant uptake about both dermatologists and allergists and we're making meaningful inroads in reaching target pediatric dermatologists and pediatric allergists. In addition, market access coverage is already at or near levels of the adult population. Asthma is a significant opportunity in Dupixent is well positioned for continued growth.
Dupixent's differentiated clinical and safety profile continues to support uptake. The asthma biologic market has expanded 13% since Dupixent's launch, demonstrating our ability to compete and grow this market. Allergists who have experienced using Dupixent in atopic dermatitis now also see its benefit for their asthma patients prescribing more prescribing among pulmonologists is also increasing and they are highly receptive to VIXon's efficacy, use in steroid dependent patients and self administration. And finally, in late June, Dupixent became the first biologic medicine approved as an add on maintenance therapy treatment for adults with an adequately controlled chronic rhinosinusitis with nasal polyps. This indication is yet another 1st in class opportunity for Dupixent given the high unmet need.
In the U. S, up to 90,000 adults with chronic rhinosinusitis with nasal polyps are considered uncontrolled despite prior surgery or systemic corticosteroid use and about 55,000 patients are those that had a prior surgery. Importantly, many patients with this disease have other type 2 inflammatory diseases like asthma in our 2 phase 3 clinical trials Almost 60% of patients also had asthma, which was improved with the Dupixent treatment. Our commercial efforts are focused on ENT's and allergists, and we're having constructive payer discussions. While early in the launch, we believe this will be a meaningful growth opportunity for Dupixent, and we look forward to providing future updates In closing we're excited about our near term performance and confidence that our ongoing commercialization efforts will drive long term growth across
For the second quarter 2019, Regeneron executed well and delivered solid financial results on both the top and bottom lines. And as Len stated, we are pleased that the Sanofi antibody collaboration has reached commercial profitability. Total revenues for Regeneron grew 20 percent year over year to $1,930,000,000, driven by continued growth of our core brands. EYLEA and Dupixent. Non GAAP diluted net income per share grew 10% year over year to $6.02 on non GAAP net income of $690,000,000.
Our 2nd quarter GAAP results were impacted by both the Alnylam upfront payment and equity investment. In addition to Marion's earlier comments about EYLEA, I want to highlight 2 additional items related to U S EYLEA net sales for the quarter. First, Inventory movements were immaterial in the quarter. 2nd, U. S.
EYLEA net sales were impacted by an increase in sales related deductions. Moving to our collaboration revenue line items. Starting with Bayer, ex U. S. EYLEA net product sales, which are reported to us by Bayer, were $715,000,000, representing a 7% reported and a 13% constant currency basis increase year over year.
Total Bayer collaboration revenue for the second quarter of 2019 grew 10% year over year to $289,000,000 of which $269,000,000 was derived from our share of net profits from Eylea sales outside the U. S. For the Sanofi collaboration, we generated significantly improved results. Total Sanofi collaboration revenue was 349,000,000 up 47% year over year. This increase was primarily driven by improved profitability in the Sanofi antibody collaboration, In the second quarter of 2019, Regeneron recognized a profit of $39,000,000 in connection with the commercialization of non IO antibodies, compared to a loss of partly offset by an increase in commercialization related expenses to support ongoing Dupixent launches.
Based on our current projections, we anticipate increasing profitability from the commercialization of non IO antibodies going forward. Turning now to expenses. Non GAAP R and D expenses were $589,000,000 for the second quarter of 2019 compared to $470,000,000 for the second quarter 2018 and essentially flat compared to the $583,000,000 recognized in the first quarter of 2019, driven by continued investment in our research platform and pipeline. Our non GAAP unreimbursed R and D expense, which is calculated as the total non GAAP R and D expense less R and D reimbursements from our collaborators was $423,000,000 for second quarter 2019 compared to $286,000,000 for the second quarter 2018 and $419,000,000 for 1st quarter 2019. The year over year increase is primarily driven by higher spend associated with our earlier stage pipeline, clinical trial and manufacturing cost support ongoing development programs and lower Sanofi reimbursement as a result of the amended immuno oncology discovery and development agreement.
Based on the current progress in our R and D pipeline and outlook for the remainder of the year, we are tightening our previous full year 2019 guidance for non GAAP unreimbursed R and D to $1,625,000,000 to $1,710,000,000. Next, non GAAP SG and A expense $375,000,000 for the second quarter of 2019, a 16% year over year increase, driven by commercialization related expenses to support ongoing Dupixent launches and Eylea's recent launch in diabetic retinopathy. We are tightening our previous full year 2019 guidance for non GAAP G and A to $1,530,000,000 to $1,580,000,000. Sanofi reimbursement of Regeneron commercialization related expenses A line item found within Sanofi collaboration revenue was $123,000,000 for the second quarter of 2019. Guidance for Sanofi reimbursement of Regeneron commercialization related expenses to $500,000,000 to $530,000,000.
Turning now to taxes, For the second quarter, our GAAP effective tax rate was 14.1 percent. We are reaffirming our full year 2019 GAAP effective tax rate guidance of 11% to 13% To assist with modeling, principally due to the Alnylam $400,000,000 upfront exclusion from non GAAP earnings, The full year 2019 non GAAP tax rate will be higher Turning next to our balance sheet and cash flow. Regeneron ended the 2nd quarter with cash and marketable securities of 5,550,000,000 Through the 1st 6 months of the year, we generated free cash flow of $916,000,000. We calculate free cash flow as net cash provided by operating activities less capital expenditures. Capital expenditures were $995,000,000 for the quarter 169 $1,000,000 year to date.
Based on our updated capital spend plan and year to date spending levels, we are lowering and tightening our full year 2019 capital expenditure guidance to $380,000,000 to $420,000,000. In conclusion, we're very pleased with our operational and financial performance this quarter These financial results, along with the execution on our R and D and commercial strategies, position us for continued long term growth. With that, I'd like to turn the call back to Justin.
Thank you, Bob. That concludes our prepared remarks and we'd now like to open the call for Q and To ensure that we are able to address as many callers as possible, please limit
Thank you. Session. And our first question is from Carter Gould from UBS.
Good morning. Congrats on the Sanofi collaboration tipping over into profitability. And thanks for taking the question. 1 for George. Wanted to ask around the CD20 antigen loss you observed at disease progression and some of the patients responding to 1979.
Was interested in your current understanding of the mechanism play here given I believe this was rare with Rituxan and how you see this potentially, ultimately influencing how 1979 may be positioned in the treatment paradigm? Thank you.
I have to admit, I didn't quite get your question there.
Okay. It was around
the CD20 antigen loss you saw in some of the patients treated and how you see that ultimately potentially influencing how the drug gets positioned in the treatment paradigm if it, potentially takes away salvage options.
Right. Well, I think that we have seen antigen loss of both CD20 and also CD19, which has occurred. So far, it doesn't seem to have in these very late stage patients dramatically affected the response rates or the durability. So we're seeing, the rates that we responded, we reported. So it doesn't seem like it's at this point the major issue.
Our next question is on.
Matthew Harrison from Morgan Stanley.
Hey, good morning. Thanks for taking the question. I guess I wanted to ask on the initial BCMA data that you expect to present towards the end of this year. I mean, how should we think about relevant comparisons here? Is this something you would compare against CAR T against BiTEs.
I'm just wondering how we should think about that and what the goal here is. Thanks.
Well, it's Lynn. Maybe George has more comments, but I would say, best thing is probably to wait for the data, but, the way Sanofi and Regeneron are thinking about that and this part of the collaboration is that, obviously, if we can deliver anything close to what a bispecific can deliver, then that a CAR T can deliver, excuse me, then a bispecific being off the shelf and a pharmaceutical like drug pricing, consideration, things like that should obviously have a huge advantage in the marketplace. So we would consider our competition more of things like the BiTEs and what have you. Obviously, we have already started out with long lasting molecules. They're well designed.
They may we make them straightforwardly through a proprietary approach. We think that we can compete and what you should be looking for is what kind of activity we can deliver. So maybe we should just wait
for that. Yes. And I think just to add that I think that, obviously, we're hoping that it's going to confirm that our class of CD3 bispecifics are reproducibly sort of top of the class in terms of producing the sort of efficacy that we've already seen with our CD20xCD3 bispecific. And so that's what we're hoping for. In addition to that, we just want to point out that both with our own pipeline and obviously with our partners pipeline, there are a myriad of combination opportunities.
So it's just sort of the beginning to show the activity with the BCMA by specific, we can then add to it with the right set of combinations with components that both sides in the collaboration have to offer that we're very excited about. Including, for example, our co stems, which we have quite a few that could potentially collaborate clinically with the BCMA by CD3 bispecific. Thank you, Matthew. Next question?
Our next question is
congrats on the antibody JV profitability as well. Maybe just 2 on Dupixent. First on, I was wondering if you could share your thoughts about the relevant size of the six to eleven year old population here at the topic derm. And then, would the pace of uptake be similar or faster than what we saw with adults in your view? And then on doobie for grass allergy, thanks for the additional data.
Just wondering next steps there for that program, if you could give us any more color on the forward. Thank you.
So why don't we take the do, Marion, we'll take the commercial question first.
Sure. And then, Terrance, just to clarify, your question on Dupixent talking about the European populations or were you talking about U. S. Populations?
Sure. I mean, both would be great, but, but yeah, I know you got the, you had the data this morning from 11. And again, I don't think you guys have characterized how big those groups are.
Right, right. So what I wanted to share with you is, obviously, with the atopic dermatitis population in the U. S. For adults, we've said about 300 to 400 1000 patients are at greatest, greatest need of therapy. And I just want to lend the context that at this point, while we're very pleased with, with uptake and the difference that Dupixent is making in the lives of patients, We've probably only so far reached about, oh, high teens, about 18% of the adult patient population.
We're excited about the adolescence launch and we're seeing nice uptake there early days. Again, a lot more work to do We haven't yet given a characterization in the size of the pediatric population, but certainly will in the future as we get further into the the data readouts and preparedness for launch of that indication, which certainly I can confirm will be will be prepared to launch as soon as we have the FDA approval.
Yes, just a slight follow-up on that. The uptake of the cream that was, I mean, Eucrisa was fairly brisk, I think, in some of the younger patients. So, we think that market is really one of great unmet medical need. And as George said, these are children we study that had 60%, 60% of their body covered with lesions having all sorts of effect on their mental health, their sleeping, the family, their just ability quality of life. So I think that, in the severe patients, we would back to pretty brisk uptake, but it's going to obviously take some work because you're treating, children with a biologic, we still have to constantly educate, and remind people what distinction to other biologics where you see an increased infection, if you are listening carefully, George mentioned that there's actually a numerically decrease consistent that we've seen this, of course, severe and moderately severe atopic dermatitis patients have deep and numerical decrease.
So we think that As people get more and more and more comfortable with the safety and efficacy, this will move lower and lower down into the age groups as we get approval. George, you maybe want to turn to the grass allergy and what's next?
Yes. So as I mentioned, we were I'm very excited by the potential of Dupixent to apparently increase the tolerability of SKIT therapy. I may have misspoke. Obviously, if there was 25 patients per arm and I said 30 patients discontinue was 30% of the patients discontinued on Skit, which I think is about normal. Obviously, if you do the math, that's about 8 patients.
That's the exact number. But in any case, So as we noted, the ability of desensitization therapy to work is real, but it takes time and it comes at the cost of tolerability in many patients not being able to get through the therapy because of the severe allergic reaction. So It is obviously very exciting to see Dupixent have, such an apparent benefit, albeit in an early study in small numbers, on the tolerability of the Skit therapy. We have a number of other ongoing programs in studying allogene. I think we're going to be looking at all of these together before we come up with our formal strategy of how to go forward in this.
But we do think that this is a very exciting area that can make a lot of difference to a lot of people who are suffering from allergy. So we're pretty excited.
Our next question is from Yaron Rober from Cowen.
Okay, great. Thanks for taking my question. And again, nice results. I have if you don't mind, just two questions. The first one on Dupi, if you can just give us a sense across between asthma AD and obviously chronic rhinosinusitis obviously just getting going.
But what really kind of led to the growth this quarter on a quarter over quarter basis and in asthma, where are you getting the majority of sales? Is it new to biologics or is it switching from biologics? And then just a question on Eylea, whether we're hearing some reports from the field that there is now a slightly higher discounting program from Regeneron about a 4% And does that jive with what you're saying? Thank you.
So before Marion tackles those questions, I'll say it is Justin's first call and maybe he's being nice to We said one question per. That was 3. We'll let Mary to give you a pass on and try and deal with these things.
Sure. I'm happy to. I'm going to start with EYLEA. And let me first comment that, we believe that physicians should make the choice on which anti VEGF therapy they want to select for their patients. And certainly EYLEA is the the standard of care for many prescribers.
Further, I'll just say that we're really not commenting on pricing strategy. I'm happy to go on to some of the other items as well. I'll see if I can remember the questions. We haven't given for Dupixent we haven't. It's early days for many of our indications, so we haven't given breakout of business by indication because it would be premature.
But I think your question, there were a couple of specifics in there that I can give you. You were asking for a characterization in asthma of the types of patients that are being prescribed Dupixent. And we are getting, the majority of our starts from bio naive patients, about 80% of our business is, patients who are coming on to biologic therapy and then, of course, the remaining are switches. The characterization I'll give you is that certainly for the physicians who are prescribing both allergists and pulmonologists now, allergists obviously had a lot of experience with Dupixent from atopic dermatitis, but we are hearing very positive comments. And it's the differentiation of the clinical profile, the safety, the results they're getting in terms of the patient's ability to breathe more easily and to go about their lives in a normal way.
That obviously coupled with the ability for patients to self or have at home administration. So certainly asthma was a major contributor to our performance in the quarter, but as was atopic dermatitis, we continue to see substantial growth, and as I mentioned earlier, there's still so much unmet need, certainly with adults. And now we're very excited to also be helping those, those adolescent patients who are very much in need. So I think I would round it all up by saying that it's the combination of indications, the expansion of our platform with Dupixent that is contributing to this strong second quarter performance.
Yes, thanks, man. I just maybe add one thing to emphasize. You said the combination vindications. That's really resonating well, for people, for example, who have both asthma and nasal polyps, which is very commonly coexisting or asthma and atopic dermatitis, particularly in adolescence is a common code system. So the ability to treat these comorbidities is a real advantage for our product.
And I think the allergists in particular, who are the ones that sort of the center point seeing patients who have multiple comorbidities are really getting there. Thanks,
Jerome. Next question.
Our next question is from Jeff Porter from SVB Leerink.
Thank you very much and congratulations on the quarter. A lot of things that I could ask questions on, but I'll just ask one with 10 subparts. On the 1979 study, George, you mentioned that going to enroll both DLBCL and follicular lymphoma and presumably also mantle cell. Do envisage could be potentially pivotal in all those NHL subtypes. And will you be enrolling patients who have prior CAR T failures in that trial?
Thanks.
Yes. So basically, the way our Funeral Phase 2 study is designed is with a number of arms actually each one dedicated precisely to exactly some of those subtypes that you're interested in so that, yes, Each one we would consider to have pending, of course, how active in the data and the durability and so forth. Each one would have rational possibility. And we also have a in the fiddle phase 2, we certainly will have the late stage follicular lymphoma patients, the late stage DLBCL patients, but also we have a program where we're focusing an arm specifically on CAR T failures where we think obviously in such a high unmet need population where people have failed everything if one sees the sort of activities that we're seeing in this very small numbers of patients so far being maintained and being durable, that, yes, that could also be a separate approval opportunity.
That's 2 out of 4 prior Cartiva George mentioned with complete responses, was very encouraging.
Okay. Thank you, Jeff. Next question?
Our next question is from Cory Kasimov from JP Morgan.
Hey, good morning guys. Thanks for taking my question. I recognize this is probably a difficult one to answer, but it's we're frequently assets. I'll ask you. And kind of how are you broadly thinking about the longer term outlook for Eylea when you balance the possibilities of healthcare reform and Part B exposure pending competition, wet AMD and then your own new EYLEA launches and less exposed indications?
Thanks.
Yes. Well, obviously, it is a difficult question to answer and we hope you give a good answer to it. Our view is, is more qualitative. If you look at the brand, we're seeing good growth and the good growth is not just occurring in the United States, it's occurring. I think it was, about 13% outside the United States.
For a brand that's this large and this late in the class, That says that the demographics that we predicted would be having a positive impact. So I do think there is plenty of room for growth. In terms of competition, obviously, as I think was mentioned on the call, the end of the day, vision and maintaining improving vision is the gold standard. It's what the FDA measures you buy. I think it's what most patients care most about, and we are unsurpassed in that.
Our long term safety think we've given over 25,000,000 injections. We are expecting action on our prefilled syringe, which we booked hard at, to come up, 2 for dates coming up pretty soon. So our enormous safety database, is, I think, gonna work in our favor. It is hard to do this And you're injecting 20, as we said, now up to 25,000,000 injections into the eye, you have to be able to do that in a very reliable and say way. If you look at some of the studies out there, that have been focusing on, let's say, dryness, there's also, if you look at them, there's some data that's worth inspecting on the reactions in terms of inflammation.
So we'll still have to see how that all sorts out. Plus we have the advantage of being able to give the dose a monthly as well as every other month as well as all the indications. So I think we're well positioned for the near term. In terms of your question about healthcare policy and the overhang. Obviously, we watch that carefully.
We're very involved in Washington. We know what's really important to us. We are sympathetic to the notion that some have that prices in the United States are much higher in prices for the same drugs outside the United States, but we don't think that the solution of tying prices in the United States for a drug like Eylea where we don't control the price outside the United States makes a lot of sense. That would be a huge negative to the biotechnology industry as a whole, because so many biotechnology companies license away their rights for survival outside the United States and they don't control the prices. So we were happy to see in the Grassley widened compromise that that was not in there.
It almost got in there in an affirmed way that it couldn't happen that vote was 14% to 14%. We watched that carefully. We're working at it. And so, we're hopeful that the policy debates that are taking place will not block innovation or reward the good actors. We haven't had a price increase in Eylea.
So the notion of having an inflation rebate would not affect us. So maybe that's a qualitative summary of all the things that we worry about. We worry about competition. Obviously, we worry about the environment. We worry about the the regulatory and patent exclusivity and so forth.
Next question.
I might pick up on one thread in the question. And this was just related to Eylea and our indications and obviously the growing indications, which recently launching in diabetic retinopathy, Today, 60% of our sales are now coming from wet AMD. And, with the expansion of our diabetes, indications now over 30% of EYLEA sales are coming from the diabetes indications and of course, recently including diabetic retinopathy and the balance for others.
And our next question is from Evan Sigerman from Credit Suisse. Hi, all. Thank you so much for taking the question and congrats on the progress. One combo for Bob and Marion. So, Bob, you had mentioned that there was some sort of an Avastin shortage may have benefited EYLEA sales in the quarter?
And then more broadly speaking, how are you positioning EYLEA in light of upcoming competitive launches?
Sure. So let me, let me take a start. And then if Bob has elements to add, so I think first, Let me talk a little bit about the 2nd quarter. We certainly had a strong quarter. It was influenced by a few factors.
And let me cover those. Certainly, there's market expansion and consideration. We do see growth from our wet AMD and DME indications. We began launching in diabetic retinopathy as mentioned, we added customer facing personnel to focus on our diabetes indications. There was a modest, what we had characterized as a modest impact from Avastin shortages in some geographies in the U.
S. And then as well, we were up against a somewhat weaker 2018 second quarter comparison. So I did want to give some relative context there. I think in terms of, as we look forward, we do think that, for Eylea as a standard of care with 8 years in market, it's important to look at growth rates. As the average of several quarters to get a true sense of what the growth profile has looked like historically and may go in the future.
And then in terms of preparation for competitive launches, we feel very well positioned to continue to perform well in the market with EYLEA. And certainly, we're very excited about the breadth of indications and the profile that Lynn just covered related to Eylea.
Our next question is from yatin Suneja from Guggenheim Partners.
Hey guys, congrats on all the progress and thanks for taking my question. The question is on REGN 3500, the IL-thirty three antibody that you have. Could you maybe talk about the development strategy there? Given that Dupi monotherapy was numerically better than IL-thirty three across all the endpoints evaluated in the asthma trial. Could you maybe comment on the areas where you think IL-thirty might play a differentiated role relative to Dupi?
As you said, the hope would be that there might be particular patients who might better respond to, for example, or would like the alternative in IL-thirty three as opposed to a dupi in asthma. And of course, We're also waiting for upcoming data from our atopic dermatitis program and also from our COPD program. To really understand how we're going to position this. But we do think that this could be an important alternative option for some patients with asthma just based on the current data and we're waiting for more data to see how it evolves.
Thank you. Next question please.
Our next question is from Mohit Bansal from Citigroup.
Great, good morning and thank you for taking my question. A quick question on Praluent, given that the challenges you are facing in the market, do you think there comes a point where you and your partner take a tough business decision or you think you can turn it around and achieve profit profitability for this drug in longer term? Thank you.
Yes. Obviously, this is a highly competitive space. And we don't want to get too detailed about what our strategies are. Obviously, we said we're trying to match our investments appropriately We do have some strategies. At the end of the day, heart disease is still a major killer.
The PCSK9 is still a terrific drug. So maybe that's all we should say at this point.
Okay. Thank you. Next question, please.
Our next question is from Kennen MacKay from RBC Capital Markets.
Hi, thanks for taking the question. Maybe one for George. I was wondering just comment a little bit more on the high dose of Fibrocept trials you're initiating and sort of how high you can go on dose and really what the goals of the high dose treatment are? Thank you. Well,
obviously from our earlier studies, we've seen that about 50% of patients can do well with a more prolong dosing schedule that is on a 12 week interval. And so we're imagining that if we go to a higher dose of of flimbercept, we may be able to push a higher percentage of patients to either a 12 week or maybe even a 16 week regimen. So, so we're running the studies to actually test these longer intervals and see whether the higher doses will actually do that. So We'll see.
Great. Next question please.
Our next question is from Alethia Young from Cantor Fitzgerald.
Hey guys, thanks for taking my question. Congrats on the very good quarter. I guess I found the 18% or so number. I'm very striking about how much penetration you've had in adults. So maybe can you talk about some of the things that you're doing to drive penetration or is it just a slow but sure process to get more people on the drug?
Thanks.
Sure. So this, I believe your question, Alicia is in reference to the comment on Dupixent, in adult atopic dermatitis. And I do yes, just to give context, but my comment is to make the point that while certainly many adult that had very, very difficult moderate to severe disease, are now being treated. There is tremendous potential for us to do more with Dupixent to help appropriate adults in need of therapy. And to your characterization, I do think that, Dupixent is gaining momentum in atopic dermatitis, certainly in other indications as well.
And it's not unusual for physicians first to prescribe to those patients who are their toughest patients, the most severe patients, we're seeing pickup in breadth and depth of physician prescribing of Dupixent And we also are seeing more moderate, moderate, severe patients being treated. So it's encouraging because Dupixent is helping these patients in a way that we hear time and time again is transformational to their lives and as well transformational to the lives of the physicians who are treating them.
I think we have time for 2 more questions, John.
All right. One is from Hartaj Singh from Oppenheimer and Company.
Great. Thank you for my question. I just have one question on Libtayo. You had a stronger number than we expected for the second quarter. I think this PD-one, has gotten some really good data and just from what we've heard is being really accepted broadly.
Can you just give some color on the commercial rollout and how that is progressing? And any thoughts also on the lung cancer trial, if you got ongoing?
So I will give some comments related to commercial performance. And with Libtayo, we certainly are making inroads to become the standard of care for CSCC patients as described in our label, approximately 90% of new patient starts in CSCC see within the anti PD-one, PD L1 class are now going to Libtayo. Further, we have excellent payer coverage that has already been achieved. And we'll further, we'll have our permanent J code on October 1st. So certainly we've made a strong start in the launch of CSCC for Libtayo.
About the lung cancer, I guess, early on, there were a lot of thoughts that the PD-one space would be commoditized and that there would be so many PD-1s and it'd be sort of boiler plates just make another one. I think that if one fairly looks at the data, these are not behaving the same. And that's obvious for sure in the lung cancer space, where KEYTRUDA is the unquestioned leader. And so we're very excited about the fact that we think that, our PD-one might have very good activities already demonstrated in as we've heard in certain settings. So we're excited to see how it's going to perform in the lung cancer setting and whether it will be one of the rare PD-1s that can really provide a lot of benefit to patients there.
And our last question from Brian Skorney from Baird.
Hey, good morning guys. Thanks for taking the question. 2 quick ones. Obviously, bevacizumab is the most described that Geoff Therapy, despite being off label. It looks like there's one company planning on actually filing a BLA next year to market a branded bevacizumab.
How do you guys think about the market impact of an active sales force marketing bevacizumab versus more passive usage right now? And then just real quickly on Regeneron 4461. I know Lapton was a pretty well researched target about a decade or ago. Never quite realized it's from. Can you just share your thoughts on what targeting the receptor with your antibody and attractive and how it could overcome some of the prior history?
Thanks.
Sure. Just very briefly because we run out of time, I'll take the bevacizumab question, George, you'll deal with the question on the insulin. I mean, on the leptin receptor, So in terms of bevacizumab, obviously, you can't have a biosimilar to bevacizumab in terms of approvals, because it doesn't have any approvals. So somebody, if they want to get approvals, obviously, it's going to have to do all the different studies, etcetera. And we already know that in large studies conducted independently by the government, for example, example, protocol T, bevacizumab was inferior, clearly inferior to Eylea.
So I think that the use of bevacizumab is mainly one driven by its off label exceedingly low price. So having another competition there, with or without a sales force, so the doctors are well aware about this, we wouldn't expect to have a major impact on the market. George, on the left hand side,
Well, just to remind you, one of the major problems with leptin and metro leptin as it was developed was that it elicited, unfortunately, a significant percentage of patients, antibodies against the leptin. And a lot of these patients are patients who actually still have endogenous leptin activity. So when the antibodies come on board, the patients end up not only neutralizing the injected left in, but their endodges left in, they end up being worse off than they were beforehand. And then they're also left with nothing to actually being available to treat them because you now can't give them leptin. So of course, we are pursuing our left in receptor activating antibody in that setting, but it would also provide a better alternative and would allow broader usage.
There are other settings where one could have conceived using metroleptin, except one wouldn't have not wanted to elicit this, antibody response and have the potential to wipe out the endogenous left in remaining activity. And so people were reticent to explore more broadly in other settings. So On top of that, it is one of the first examples of our new activating antibody technology that allows us to, we hope, create efficient in vivo acting activating antibodies for growth factors and cytokines and so forth. So for all those reasons, we're pretty excited about our left in receptor program, but of course, we'll be starting in the in the same sort of rare patients where leptin is mostly used right now.
And I'll now turn the
call back over. To Justin Hochul for closing remarks.
Great. Thank you, everyone, and thank you again for dialing in to the call today. The IR team will be around to answer your questions later today.
Thank you, ladies and gentlemen. That concludes today's conference. Thank you for participating and you may now disconnect.