The pharma and biotech industries saw a number of pivotal trial completions, positive data readouts and new drug application (NDA) submissions during 2022, which portends approvals across a range of indications in 2023. But while a few drugs aim to be first-movers or best-in-class in their respective indications, many of the candidates aim to offer unique advantages over existing products. In other words: Welcome to the era of improved patient experience and convenience.
Oncology is always a busy development area, and 2023 will see material approval decisions in the liquid tumor space that offer alternatives to existing CAR-T therapies. Roche stands out among oncology players with two CD20xCD3 T-cell engaging bispecific antibodies — mosunetuzumab and glofitamab for follicular lymphoma and diffuse large B-cell lymphoma, respectively.
Despite different target populations, both drugs act in a similar way and offer significant efficacy and administration advantages over CAR-T therapies. Johnson & Johnson’s teclistamab aims to be a more durable B-cell maturation antigen (BCMA)-targeting drug for multiple myeloma, with similar advantages over CAR-Ts as well as other BCMA bispecifics.
In the solid tumor pipeline, smaller biotech firms Menarini and Radius Health are soon to release Phase III data for elacestrant in breast cancer, which has the unique potential to serve a niche and underserved genetic patient subset in a broad indication still in need of treatment options.
Hematology has a big year ahead with potential game-changing approvals for the hemophilia community. Two Food and Drug Administration approval decisions for hemophilia A are anticipated in February: the Sanofi/Sobi factor VIII replacement therapy efanesoctocog alfa and BioMarin’s gene therapy Roctavian. UniQure and CSL Behring also await an FDA decision for their gene therapy etranacogene dezaparvovec for hemophilia B. While gene therapies for hemophilia are highly anticipated — their durability offers invaluable convenience and enhanced quality of life — pricing remains a question mark.
As in prior years, the autoimmune disorder space is generating interest and investment. In 2023, the spotlight’s glare will turn to gastroenterology, with two drugs aiming to secure approvals for ulcerative colitis. Pfizer awaits a decision for its oral S1P modulator etrasimod, which offers improvements over JAK inhibitors, while Eli Lilly anticipates a verdict on its potential best-in-class IL-23 biologic.
Over in neurology, beta-amyloid-targeting agents are maintaining industry buzz despite the controversial approval — and commercial failure — of Biogen’s Alzheimer’s disease drug Aduhelm. In partnership with Eisai, Biogen is continuing its attempt to remedy the debilitating disease with a similar agent, lecanemab. The drug yielded some convincing cognitive decline data this year in mild and early Alzheimer’s patients and could see either an accelerated or traditional approval in 2023.
Meanwhile, Lilly’s donanemab appears fairly close behind on the approval path: It’s currently under review for a possible accelerated approval as the company awaits a pivotal Phase III readout next year.
As for the metabolic disorder space, diabetes powerhouse Novo Nordisk is vying for an approval of its touted “insulin upgrade” after completing six robust Phase III trials of insulin icodec in both type 1 and 2 diabetes. Intercept’s Ocaliva is being prepped for a second attempt at becoming the first drug approved for non-alcoholic steatohepatitis (NASH), though mixed recent data suggest a degree of uncertainty. Then there’s Lilly’s positive Phase III results for tirzepatide in obesity, which has upped anticipation for further Phase III readouts in the months ahead.
Other highly anticipated 2023 approvals aiming to expand options for underserved populations include Pfizer’s RSV vaccine for older adults, which would be the first of its kind. An Astellas drug for menopause symptoms, fezolinetant, is also up for an approval decision, offering an overlooked patient population a more clinically meaningful treatment option.
GSK’s daprodustat for renal-related anemia is in line for approval, but safety questions surrounding its drug class may breed skepticism at the final FDA review stage. Finally, Lexion’s sotagliflozin, originally approved for diabetes, offers a compelling case for the treatment of ejection-fraction agnostic heart failure.
Agents profiled in this report were chosen in consultation with InThought Research, Ipsos and Adis-Insight. Analyses of featured products include clinical data, revenue forecasts, expected launch dates and likelihood of success updated as of mid-October 2022.
Drug: Lunsumio (mosunetuzumab)
Company/stage: Roche, pre-registration
Indication: Relapsed or refractory follicular lymphoma
Clinical trial data: Lunsumio is a CD20xCD3 T-cell engaging bispecific antibody. In the Phase I/II GO29781 study, after a median follow-up of 18.3 months, the complete response (CR) rate was 60% and objective response rate (ORR) was 80%, while median duration of responses was 22.8 months. An EU approval was granted in June 2022, while an FDA decision is expected on December 29 for a 2023 launch.
InThought comment: While Blincyto (blinatumomab), a CD19XCD3 bispecific antibody, is marketed in B-cell acute lymphocytic leukemia, this would be the first clinically meaningful bispecific antibody to be approved in the U.S. for non-Hodgkin’s lymphoma patients. While anti-CD19 CAR-T therapies have been immensely successful in non-Hodgkin’s lymphoma, Lunsumio offers an advantage of being off-the-shelf (no wait time for manufacturing) and is easier to administer in the outpatient setting. While side effects are similar to those of CAR-Ts — cytokine release syndrome (CRS) and neurotoxicity — they seem well-managed with a potentially lower likelihood of hospitalization. — Lavan Khandan, senior principal
Peak sales: $250 million by 2025 (Credit Suisse)
Ipsos comment: As an off-the-shelf therapy, Lunsumio can quickly be administered, circumventing the prolonged manufacturing, logistical and administration challenges of CAR-T therapies. It provides an important new option for relapsed/refractory follicular lymphoma patients after two or more prior treatments. Data from clinical trials have also shown that bispecific antibodies can achieve responses in patients who have previously received CAR-T therapy. Lunsumio is poised to compete directly with Gilead Sciences’ Yescarta and Novartis’ Kymriah, which both won third line-plus FDA approvals earlier this year. — Brian Kayen, VP oncology (U.S.)
Company/stage: Roche, pre-registration
Indication: Relapsed/refractory diffuse large B-cell lymphoma (DLBCL)
Clinical trial data: Glofitamab is Roche’s other CD20xCD3 bispecific antibody. In the Phase II NP30179 study in relapsed/refractory DLBCL patients — 59% refractory to initial therapy and 32% refractory to CAR-Ts — 39.4% of patients achieved CR and 51.6% achieved ORR. A submission is expected in the second half of 2022 for a potential PDUFA in 2023.
InThought comment: Glofitamab is similar to Lunsumio but for a much larger subtype of non-Hodgkin’s lymphoma. It will go up against AbbVie’s epcoritamab and Xencor’s plamotamab with a first-mover advantage: It has a similar profile to Lunsumio in terms of efficacy/safety and delivery, but with a potentially faster onset of action because of its two CD20 arms. However, it’s unclear whether this will prove clinically meaningful. Glofitamab is also suitable for patients who are too sick to wait for CAR-T manufacturing. — Khandan
Peak sales: $200 million by 2025 (Credit Suisse)
Ipsos comment: With potential CAR-T efficacy and a durable response, glofitamab will provide a readily available choice for CAR-T failures or non-candidates. Despite requiring IV infusion, fixed-duration treatment might be a tempting proposition by eliminating the need to treat until disease progression. A manageable toxicity profile also makes it a good partner for combination therapies and glofitamab is being investigated in earlier lines of treatment. — Agata Atkins, associate director, global oncology monitor
Drug: Tecvayli (teclistamab)
Company/stage: Janssen, pre-registration
Indication: Multiple myeloma
Clinical trial data: Tecvayli is the first of a class of BCMA X CD3 bispecifics to be submitted for approval in multiple myeloma (MM). In the Phase I/II MajesTEC-1 study in 165 patients, 63% achieved ORR, 58.8% achieved a very good partial response (VGPR) and 39.4% achieved a CR or better. The median duration of PFS was 11.3 months and median duration of overall survival was 18.3 months. The most common adverse events were cytokine release syndrome (72%) neutropenia (71%) and anemia (55%). An EU approval came in August and an FDA decision is expected soon.
InThought comment: Tecvayli will go up against other BCMA-targeting candidates for MM, such as GSK’s Blenrep. While Tecvayli has a comparable response rate, it has a higher durability of response. Bispecifics can better mount an immune response against MM cells without the keratopathy side effects seen with Blenrep; those side effects have resulted in prescribing hesitance. As an off-the-shelf treatment, Tecvayli is easier to administer than anti-BCMA CAR-Ts for a broader set of patients and has performed well compared to BCMA bispecifics from Pfizer and Regeneron. — Khandan
Peak sales: $230 million by 2025 (Credit Suisse)
Ipsos comment: WA European approval solidified Janssen status as a leader in MM. While Tecvayli will compete with BCMA-targeting CAR-Ts (including BMS’ Abecma and Janssen’s own Carvykti), Janssen sees it as fulfilling a role for patients for whom CAR-T is not an option due to logistics, contraindications or other reasons. — Eric Blouin, SVP, oncology (U.S.)
Company/stage: Menarini/Radius Health, Phase III
Indication: Breast cancer
Clinical trial data: Elacestrant is an oral SERD. In the Phase II Emerald study, PFS at 12 months with elascestrant was 22.7% in the overall population versus 9.4% with standard of care (SOC), and 26.8% in the ESR1 mutation population versus 8.2% with SOC. Elascestrant significantly reduced the risk of disease progression or death by 30% in all patients and 45% in patients with ESR1 mutation.
InThought comment: While SERDs have a checkered history in breast cancer, given prominent failures from Roche and Sanofi, elacestrant’s pivotal trial included a specific patient subset that showed particularly promising results. While its approval could be limited to these patients, the drug should still find a meaningful market in the large breast cancer space. — Khandan
Ipsos comment: While Menarini is likely to get a place in the HER2- HR+ Stage IV breast cancer market, one of the challenges will be how to educate physicians on the best treatment strategy for the hard-to-treat endocrine-resistant patients. Additionally, the genetic test to identify the ESR1 mutation is not yet broadly used and might create a temporary barrier for uptake. — Alessandra Franceschetti, senior director, global oncology monitor
Drug: Efanesoctocog alfa
Company/stage: Sanofi/SOBI, pre-registration
Indication: Hemophilia A
Clinical trial data: Efanesoctocog alfa is a Factor VIII replacement therapy for the treatment of hemophilia A. Results from its Phase III XTEND-1 study demonstrated a superior efficacy to prior factor prophylaxis treatment and a clinically meaningful prevention of bleeds in people with severe hemophilia A. Notably, the study showed a median annualized bleeding rate (ABR) of 0 and mean ABR of 0.71. The drug is under FDA priority review with a decision expected on February 23.
InThought comment: Efanesoctocog alfa uses a very interesting half-life extension technology to provide high FVIII levels with once-weekly IV infusions and is clearly superior to extended half-life FVIIIs in terms of sustained high FVIII levels and dosing regimen. It also will likely provide better bleed protection than Roche’s commonly used bispecific antibody Hemlibra, especially in highly active patients who need higher FVIII levels. Additionally, some patients and HCPs would rather treat hemophilia A by replacing what is missing via FVIII prophylaxis versus a non-factor therapy such as Hemlibra. — Leon Henderson-MacLennan, medical adviser
Peak sales: $250 million by 2025 (Credit Suisse)
Ipsos comment: Current data on Efanesoctocog alfa’s efficacy, safety, lack of inhibitor development and weekly frequency of administration could be an attractive option for prophylactic treatment with factor VIII replacement therapies. But long-term data on gene therapies could change how severe hemophilia is managed. — Isabel Palau, director, global therapy monitors
Company/stage: BioMarin, pre-registration
Indication: Hemophilia A
Clinical trial data: Valoctocogene roxaparvovec is an adeno-associated virus serotype 5 (AAV5) mediated gene therapy for hemophilia A. In its Phase III GENEr8-1 trial, Roctavian demonstrated superiority to factor VIII prophylaxis, reducing mean annualized bleeding rate by 84%. It also reduced mean annualized factor VIII infusion rate by 99%. The therapy has a conditional EMA approval and is awaiting a verdict from the FDA.
InThought comment: Roctavian will be the first gene therapy approved for hemophilia A. It will offer patients a one-time treatment that will eliminate the need of prophylaxis for at least five years. However, a likely high price as well as concerns about how long it will work might prove limiting factors in its uptake. — Henderson-MacLennan
Peak sales: $899 million by 2025 (Credit Suisse)
Ipsos comment: The first therapy of its kind, Roctavian delivers functional factor VIII genes to liver cells to replenish a missing blood-clotting protein. Data from clinical trials support BioMarin’s proposed one-time therapy use of Roctavian. However, with only two years of data available so far, the EMA recommends long-term follow-up tests to verify a continued safe and effective response. — Dale Chandler, research manager, global therapy monitors
Drug: EtranaDez (etranacogene dezaparvovec)
Company/stage: UniQure, CSL Behring, pre-registration
Indication: Hemophilia B
Clinical trial data: Etranacogene dezaparvovec is an AAV5-mediated gene therapy for hemophilia B. An ongoing Phase III trial yielded promising results, with data at 1.5 year post-treatment showing significantly increased clotting factor IX activity and reduction in bleeding rates. While the trial is expected to conclude in March 2025, the FDA accepted CSL’s application for priority review in May 2022.
InThought comment: Similar to Roctavian, EtranaDez will be the first gene therapy approved for hemophilia B. It, too, has concerns of a high price tag, which may slow adoption. — Henderson-MacLennan
Ipsos comment: The development of gene therapy EtranaDez could usher in an exciting new chapter in the treatment of hemophilia B. In addition to favorable clotting factor activity and bleeding rates, 98% of participants given the full dose of the treatment also ceased prophylaxis treatment after 1.5 years. — Chandler
Company/stage: Pfizer, pre-registration
Indication: Ulcerative colitis
Clinical trial data: Pfizer’s etrasimod is a next-in-class, selective S1P modulator aiming to improve the UC treatment landscape alongside Bristol Myers Squibb’s first-to-market S1P Zeposia. In the Phase III ELEVATE UC 52-week trial, etrasimod demonstrated 27% clinical remission versus 7.4% on the placebo arm. A U.S. approval is expected in the Q3 2023, with an EU approval expected to follow.
InThought comment: While etrasimod will serve as another safer oral alternative to JAK inhibitors for UC, it’s difficult to see how it will differentiate and take market share from Zeposia. Etrasimod’s remission induction data were a little better than Zeposia’s, while Zeposia’s maintenance data was better than etrasimod. They both require the same clinical monitoring. — Adam Schaffner, senior principal and director of research
Peak sales: $113 million by 2025 (Credit Suisse)
Ipsos comment: Boasting a favorable, once-daily oral administration, etrasimod may be hoping to take advantage of this convenience to compete with the JAK inhibitors that have been the subject of safety reviews. Safety and tolerability data from the ELEVATE trials are impressive, as are the notable rates of clinical remission and endoscopic improvement. If approved, it will be interesting to monitor etrasimod’s impact on existing targeted oral options as well as the more traditional routes of therapy. — Penny Robinson, senior research executive, global therapy monitors
Company/stage: Eli Lilly, pre-registration
Indication: Ulcerative colitis
Clinical trial data: Mirikizumab is a monoclonal antibody inhibiting IL-23. In the Phase III LUCENT-2 study, 50% of patients who responded to 12-week induction treatment were able to achieve clinical remission after one year (versus 25% on placebo). An FDA decision is expected in Q1 2023, with other global approvals expected to follow.
InThought comment: Data so far indicate that mirikizumab is shaping up as a best-in-class IL-23 inhibitor. Currently approved IL-23 inhibitors have a reputation of having a slow onset of action, which is outweighed by a strong durability of response. However, mirikizumab might have its edge with similarly strong durability rates as well as a faster onset of action. — Schaffner
Peak sales: $1.12 billion by 2025 (Credit Suisse)
Ipsos comment: Mirikizumab presents a favorable safety profile in the clinical trial setting and recorded encouraging clinical remission rates and novel patient-reported outcomes. It will have a narrow window to establish itself before AbbVie’s Skyrizi and Janssen’s Tremfya join the fray. While mirikizumab displays the ability to treat patients irrespective of prior biologic experience, it is not entirely clear where the IL-23p19 inhibitors will fit in the UC treatment algorithm, so Lilly’s positioning will be critical in establishing its niche. — Chris Teale, head, autoimmune center of expertise
Company/stage: Eli Lilly/Almirall, pre-registration
Indication: Moderate to severe atopic dermatitis
Clinical trial data: Lebrikizumab is a monoclonal antibody inhibiting IL-13, which is designed to improve upon Sanofi’s IL-13/IL-4 inhibitor Dupixent. In the ADvocate 1 and 2 Phase III trials, 43% of patients achieved clear skin at 16 weeks and 33% achieved almost clear skin. Monthly doses appeared just as effective as twice-monthly doses after the 16-week induction period. A late 2022 regulatory submission points to FDA approval in 2023.
InThought comment: Overall, the data look strong compared to Sanofi’s Dupixent, with lebrikizumab performing slightly better on the IGA 0-1 scale. But the real question is whether the four-week dosing gets approved, as it represents a market differentiator from Dupixent’s two-week dosing. While both drugs have acceptable safety profiles, lebrikizumab doesn’t have any of the conjunctivitis signals seen with Dupixent. — Schaffner
Peak sales: $870 million by 2025 (Credit Suisse)
Ipsos comment: Lebrikizumab looks set to enter a competitive and vibrant advanced therapy market for AD. A greater number of prescribing options are likely to accompany augmented expectations for physicians and patients alike. Almirall/Lilly will be hoping to garner attention through the recently released long-term efficacy data of the IL-13, while the data signal a potential first in the injectable landscape for AD: four-week dosing. — Hannah Brown, associate director, global therapy monitors
Company/stage: Eisai/Biogen, Phase III/pre-registration
Indication: Alzheimer’s disease
Clinical trial data: Lecanemab is an anti-amyloid beta protofibril antibody for the treatment of mild cognitive impairment due to Alzheimer’s disease and early AD. In September, the Phase III CLARITY-AD trial in 1,795 patients showed a 27% reduction in cognitive decline versus placebo at 18 months. The drug has a PDUFA date of January 7 for accelerated approval; a full approval boosted by the CLARITY-AD data could come later next year.
InThought comment: Clinically, lecanemab may not be much better than Biogen’s Aduhelm, but trial results appear to be more robust and meaningful. They’re something that we can build on. Neurologists have embraced the positive initial results, especially as they showed an effect on all the Alzheimer’s endpoints measured. Results are likely to be similar for close beta-amyloid targeting competitors: Lilly’s donanemab and Roche’s gantenerumab. There is some talk that lecanemab might be safer than Aduhelm and the competition, with fewer signs of the common adverse event ARIA (amyloid-related imaging abnormalities). Detailed data expected in November are needed to properly speak to its risk/benefit profile. — Bennett Weintraub, president
Peak sales: $350 million by 2025 (Credit Suisse)
Ipsos comment: Should lecanemab receive approval — and win coverage by CMS — the big question will be to understand the extent to which the benefits promised by the Phase III results are clinically meaningful. In other words, will HCPs and patients “know” the drug is working as intended? This is a key question for the current anti-amyloid treatments for AD. — Scott Morano, SVP, healthcare (U.S.)
Company/stage: Eli Lilly, Phase III, pre-registration
Indication: Alzheimer’s disease
Clinical trial data: Donanemab is another beta-amyloid targeting antibody for Alzheimer’s. A Phase II study showed significant clearing of amyloid in the brain, resulting in a better cognitive score versus placebo at 76 weeks. In August, the FDA agreed to expedite its review based on early data for a potential decision in 2023. The Phase III Trailblazer study is due to readout in Q2 2023.
InThought comment: Donanemab is a little behind lecanemab, but a similar efficacy profile is expected. Lilly is trying to show that once you remove the plaque from the brain, you can stop taking the drug, which is appealing to doctors and patients. — Weintraub
Peak sales: $5.5 billion by 2025 (Credit Suisse)
Ipsos comment: Approval of Lilly’s donanemab could represent a significant milestone in the ongoing attempts to crack the Alzheimer’s code and advance the understanding of the amyloid hypothesis. Lilly will need to navigate not only FDA approvals, but also coverage from Medicare — not only for the drug itself, but also for the related diagnostic testing needed to verify the presence of amyloid required for treatment. — Morano
Company/stage: AbbVie, pre-registration
Indication: Parkinson’s disease
Clinical trial data: ABBV-951 is a 24-hour continuous subcutaneous delivery of levodopa/carbidopa prodrug for advanced Parkinson’s disease. The Phase III head-to-head trial in 130 advanced-stage PD patients showed statistically significant improvements in controlling motor fluctuations and increases in hours of “on” time without troublesome dyskinesia versus oral immediate release Duodopa (levodopa/carbidopa).
InThought comment: AbbVie is offering Parkinson’s patients the next step to its existing levodopa therapy, which requires invasive surgery to install its pump. The subcutaneous needle administration opens access to a broader range of patients, while its prodrug form of levodopa prevents extensive metabolism of the drug before it reaches the brain, which could lead to enhanced efficacy. While efficacy/safety data should suffice for an approval, there are some minor questions on whether the FDA might scrutinize its device, as it did with Supernus’ close competitor SPN-830. Market uptake is expected to be strong, giving advanced PD patients a non-surgical option. — Schaffner
Peak sales: $183 million by 2025 (Credit Suisse)
Ipsos comment: While carbidopa/levodopa agents are available orally, the novelty of ABBV-951 is the continuous dosing. This should increase “on” time, resulting in increased efficacy. The novel device, similar to other continuous pumps used for insulin, should be an effective alternative for Parkinson’s patients who struggle with oral treatments, either from dexterity issues or the potential irregularity of “on” time after taking an oral dose. — Morano
Drug: Insulin icodec
Company/stage: Novo Nordisk, pre-registration
Clinical trial data: Insulin icodec is a once-weekly injection for diabetes. Novo Nordisk has completed six positive Phase III (ONWARDS) trials in both type 1 and type 2 diabetes, demonstrating either superiority or non-inferiority versus other insulin-based therapeutic regimens currently used as standard of care. Regulatory filings in the U.S., EU and China are expected in the first half of 2023.
InThought comment: Insulin icodec’s major advantage over current basal insulins such as Tresiba, Lantus and Basaglar is its once-weekly dosing. Data to date have shown at least comparable or superior efficacy versus daily basal insulins. There have been some concerns about hypoglycemia, mainly in type 1 diabetes. Some trials in type 2 diabetes showed a numerically higher rate of hypoglycemia but was not statistically significant, while ONWARDS 6 in type 1 diabetes showed significantly higher levels of hypoglycemia. — Chris Martin, senior principal
Peak sales: $250 million by 2025 (Credit Suisse)
Ipsos comment: Insulin icodec would be a game-changer for reducing the daily injection burden and for patients starting therapy. Novo’s use of digital therapeutics to help guide patients through titration is another step forward. However, pricing a once-weekly version of common once-daily medications will need to thread a careful needle with payers and patients. A novel insulin such as icodec would be targeted at non-Medicare patients, given that the U.S. is capping costs for insulin under Medicare at $35. — Morano
Company/stage: Intercept, pre-registration
Clinical trial data: Obetocholic acid is a semi-synthetic bile acid analogue. It was approved in 2016 for primary biliary cholangitis (PBC), but its potential in NASH holds the greater market potential. In the wake of a failed attempt in 2020, new positive interim data from the Phase III REGENERATE trial spurred the resubmission of the NDA. The 931-patient study showed 22.4% of subjects taking once-daily OCA 25mg achieved at least one stage of fibrosis improvement with no worsening of NASH after 18 months, versus 9.6% on placebo. An approval decision is expected in 2023.
InThought comment: Therapies for NASH remain a significant unmet need and have been a drug development graveyard, much like treatments for Alzheimer’s. Ocaliva could fill that void, but the likelihood of its approval remains uncertain. Its pathway to approval has been marred by safety concerns, resulting in a CRL on the first attempt to approval. — Roshni Basu, senior principal
Company/stage: Eli Lilly, Phase III
Clinical trial data: Tirzepatide is a once-weekly GIP receptor/GLP-1 receptor agonist. It is currently under regulatory review as a treatment for adults with type 2 diabetes (as Mounjaro), but more eyes are on its obesity potential. Phase III data from its SURMOUNT-1 trial showed 15mg tirzepatide achieved at least a 20% body weight reduction in 63% of patients. Further Phase III results are anticipated in 2023.
InThought comment: Novo Nordisk’s Wegovy has shown the demand for effective weight loss drugs — and tirzepatide’s profile appears to be better than Wegovy in terms of weight loss. Lilly will be able to benefit from the company’s strong position in diabetes when it launches tirzepatide. Data from outcomes studies over the next few years for both drugs should lead to expansion of the use of these GLP-1 drugs in non-diabetes populations. — Martin
Peak sales: $3.9 billion by 2025 (Credit Suisse)
Ipsos comment: Lilly’s tirzepatide would be life-changing for many people with obesity. Novo Nordisk’s Wegovy has seen overwhelming demand, highlighting room in the market for an additional strong competitor. The challenge for Lilly will be to ensure access to tirzepatide in obesity. Many insurance plans still do not cover anti-obesity medications and, without coverage, costs for treatment put it out of reach for most patients. — Morano
Drug: RSV vaccine
Company/stage: Pfizer, pre-registration
Clinical trial data: The investigational vaccine is bivalent, targeting both A and B strains of the virus. Its Phase III RENOIR trial in adults older than 60 showed vaccine efficacy of 85.7% in participants with more severe disease of lower respiratory tract illness (LRTI-RSV) and 66.7% in the overall population. An approval decision is expected in 2023; Pfizer is pitted against GSK, which has a similar vaccine and regulatory submission timeline.
InThought comment: Pfizer’s bivalent RSV vaccine delivered promising results in older participants, particularly those with more severe disease. Since no RSV vaccines are currently approved, a new vaccine would have large market potential, both from a medical and commercial viewpoint. Pfizer has been close on the heels of GSK, which recently announced positive results for its RSV vaccine and touted higher overall efficacy of 82.6%. Differences in effectiveness may influence company messaging and consumer sentiment. — Ashley Ingles, senior analyst
Peak sales: $230 million by 2025 (Credit Suisse)
Ipsos comment: Pfizer’s reported efficacy in reducing severe lower respiratory tract illness in older adults, along with good tolerability and no safety concerns, is encouraging after decades of failed attempts. The vaccine landscape for RSV is on the verge of profound change, with GSK, Janssen, Moderna and Bavarian Nordic spearheading new RSV vaccines. — Lindsey Sohl, director, global syndicated vaccine study
Company/stage: Astellas, pre-registration
Indication: Vasomotor symptoms of menopause
Clinical trial data: Fezolinetant is an oral selective neurokinin-3 receptor antagonist. Three Phase III (SKYLIGHT) trials enrolled more than 2,800 participants in the U.S. and Europe. The drug demonstrated statistically significant advantages over placebo in reducing frequency and severity of moderate to severe vasomotor symptoms, including hot flashes and night sweats. The drug is under NDA review for a February 22 PDUFA date.
InThought comment: Today’s pharmacologic management, featuring hormonal approaches and ones with neuropsychiatric effects, are woefully inadequate. It appears that fezolinetant may at least provide a safe alternative for a significant proportion of women who need relief from symptoms that both adversely affect quality of life and contribute to significant morbidity. Phase III data is reassuring; notably, improvement was observed as early as one week after dosing. Interestingly, the drug failed a small Phase III investigation in China, Korea and Taiwan. However, I do not anticipate this will derail potential U.S. and EU approvals. — Henderson-MacLennan
Peak sales: $1.9 billion by 2025 (Credit Suisse)
Company/stage: GSK, pre-registration
Indication: Renal-related anemia
Clinical trial data: Daprodustat is an oral HIF-PH inhibitor for chronic kidney disease patients both off and on dialysis. Its Phase III (ASCEND) program included five studies enrolling over 8,000 patients who were treated up to 4.26 years. The drug has a PDUFA date of February 1.
InThought comment: We’ve come to understand that data show non-inferiority to large molecule stimulators of erythropoiesis in terms of key cardiovascular outcomes while maintaining, and even improving, target-range hemoglobin levels. The devil will be in the details of its safety data given that two other similar agents failed to pass U.S. regulatory muster based on safety profile. Vadadustat missed non-inferiority for major adverse CV events in the non-dialysis population, along with excess thromboembolic events and drug-induced liver injury. Roxadustat was approved in ex-U.S. markets but deemed unacceptable by the FDA due to excess all-cause deaths, major adverse coronary events, thrombotic events, infections and seizures. While robust data should lend themselves to an approval, I anticipate that continued surveillance will be required for several years. — Henderson-MacLennan
Peak sales: $910 million by 2025 (Credit Suisse)
Company/stage: Lexicon, pre-registration
Indication: Heart failure
Clinical trial data: Sotagliflozin is an SGLT1/2 inhibitor that was approved in Europe in 2019 (as Zynquista) for co-management of type 1 diabetes in overweight adults. Lexicon has been pursuing U.S. approval in heart failure via two Phase III studies. They showed a target once-daily dose of 400mg of sotagliflozin led to pronounced reductions in heart failure-related events and a similar tolerability profile to placebo.
InThought comment: Despite an approval in the type 1 diabetes setting, sotagliflozin’s promise in heart failure is more compelling. The SGLT1/2 inhibitor looks set to join AstraZeneca’s Farxiga and Lilly/Boehringer Ingelhem’s Jardiance as therapeutic options for heart failure. Its net benefit magnitude at endpoints of total cardiovascular deaths, hospitalization for heart failure and urgent heart failure is exemplary and its real-world impact is expected to be as admirable. Performance on endpoints related to overall major adverse coronary events, stroke and heart attacks suggest best-in-class potential, with the caveat of difficult comparisons. Data at ESC 2021 point toward accelerating its use in an ejection-fraction-agnostic setting. — Henderson-MacLennan