For the third year in a row, Evaluate Vantage’s most hotly tipped drug approval when it comes to future sales potential is an Alzheimer’s disease therapy, but there is far more caution in this year’s list than we have seen before.
In 2022, Evaluate’s most anticipated drug, with estimated 2026 sales worth a huge $6 billion, was Eli Lilly’s Alzheimer’s drug donanemab. In 2021, Evaluate saw Biogen and Eisai’s Alzheimer’s drug aducanumab, later approved as Aduhelm, as the top tip in terms of sales, reckoning it could make $4.8 billion in 2026.
What we have learned is that making predictions on Alzheimer’s drugs is a tough business. Donanemab did not see a 2022 approval and is back again on this year’s list, coming in at No. 4 but with a substantially lower sales estimate of just $1.9 billion by 2028.
Even that is now in jeopardy after the FDA rejected Lilly’s fast track approval for donanemab, saying it needed more data and the cwould have to apply for a traditional review, something which will push any FDA yes to next year.
And as for Aduhelm, that drug is now all but dead commercially having made just several million dollars while having the misfortune of being the worst launch in pharma history.
Evaluate sees Eisai at the top again this year with its Alzheimer’s asset lecanemab, approved in January as Leqembi, with a sales estimate of $3 billion by 2028.
Caution is a common theme in this year’s list. There are several first-ever approvals on the horizon, including for Apellis’ therapy for geographic atrophy (GA), an eye disease that can cause blindness; a vaccine against respiratory syncytial virus coming from GSK, protecting against a common cold virus that can prove fatal to the very old and very young; and Sarepta/Roche’s experimental gene therapy for Duchenne muscular dystrophy (DMD), a genetic condition that hits young boys and severely weakens their muscles, ultimately proving fatal before middle age.
There are some truly amazing innovations in this list with these firsts. But being first in pharma comes with high risks in regulation and reimbursement as well as unknowns in longer term safety and efficacy.
The FDA will likely be more cautious with new technologies, and payers may balk at new price tags, with Sarepta and Roche’s DMD therapy the most likely to come under fire. GSK’s RSV vaccine will likely be first to market with a Prescription Drug User Fee Act goal date for a decision by the FDA in May, but it already has Pfizer on its tail with its rival vaccine also set for an FDA decision in May.
Apellis has seen a rocky road to the FDA, having experienced hiccups in some of its trials and a self-inflicted delay in getting the drug reviewed, all the while contending with past failures from other pharmas, which were forced to give up on their GA therapies when trial results did not go their way.
That caution has also translated into a much smaller overall total for the top 10’s sales potential when compared to last year. In 2022, the sales potential for the top 10 drugs from Evaluate’s list came in at $26.9 billion. For 2023, it’s just $17.5 billion, a drop of nearly $10 billion, with much lower totals for the leading drugs on the most recent list.
The top 10 list is based on Evaluate Vantage’s 2023 preview, where the analysts assess what they see as the biggest-selling drugs that will be approved this year in terms of sales by 2028.
Check out the top 10 most anticipated drug launches of the year below. You can find last year’s edition here.
1. Lecanemab
By Ben Adams
Drug:Lecanemab/Leqembi
Companies: Eisai/Biogen
Used for: Alzheimer’s disease
Est. 2028 sales: $3 billion
Drug:Lecanemab/Leqembi
Companies: Eisai/Biogen
Used for: Alzheimer’s disease
Est. 2028 sales: $3 billion
We start our list much as we did last year, namely with an Alzheimer’s disease drug at the top. Eli Lilly’s donanemab was Evaluate Vantage’s No. 1 in 2022, and that honor falls to Eisai and Biogen’s lecanemab this year.
While the waters for Alzheimer’s drugs were certainly murky last year, we start 2023 with an extra layer of silt that has muddied those waters considerably.
Of course, donanemab is on this year’s list, too, given that it didn’t get approved last year, but is still gunning for that FDA green light in 2023 (and fourth on our list, check out below).
Evaluate reckoned a year ago that donanemab would have 2026 sales worth a huge $6 billion, but now that figure has dwindled to just $1.9 billion by 2028.
Add to that lecanemab is only set for $3 billion in sales by 2028, and it’s easy to see something is up. In fact, much of the murk muddying up these Alzheimer’s waters is a direct result of the FDA and Biogen, and, to a lesser extent, Eisai, and the now infamous 2021 approval of the companies’ Alzheimer’s drug Aduhelm.
Aduhelm was tipped to be a major blockbuster, but swiftly after its approval the drug’s creators Biogen and Eisai saw a commercial flop on a scale no other medicine launch has seen before. Its high price coupled with its questionable safety and efficacy were simply too much for the market to bear, and, despite being the first new Alzheimer’s drug in more than 15 years, it has all but now disappeared from the market.
But there was more: The FDA has now seen its reputation questioned over its controversial approval of the drug in 2021, coming several months after its expert panel rejected the drug for a green light.
The FDA ignored the advice to hand Biogen and Eisai an approval, but a scathing congressional report, out late last year, has detailed communications described as “inappropriate” and “atypical” between Biogen and the FDA regarding the approval of Aduhelm.
Eisai, which has been slowly removing itself from the Aduhelm saga, is now squarely focused on lecanemab, work on which is being led by the Japanese pharma with some help also coming from Biogen as the pair looks to put the Aduhelm fiasco behind it.
Like so many late-stage Alzheimer’s drugs, lecanemab works by removing amyloids, a protein that builds up in the brain and is believed by researchers to be a culprit behind Alzheimer’s. The theory is that if you clear it out, or stop its buildup, you can reduce the symptoms of the degenerative disease.
Its most recent clinical data, released in September last year, were positive for the pair, with lecanemab slowing disease progression among patients with mild Alzheimer’s by 27% compared to patients given a placebo, with effects starting at six months and continuing through the remainder of the study.
Quickly after these data were published, some researchers and analysts questioned how meaningful that 27% will be in the real world. Safety of the drug also remains a concern as there have been two trial patient deaths, specifically from a stroke and a hemorrhage, though Eisai has said it does not believe its drug is to blame.
Despite all of this, Eisai got its FDA approval in early January this year (with the drug becoming Leqembi), and is hitting the ground running on the commercial side. Last summer, the company nabbed Eli Lilly’s former Alzheimer’s and marketing lead Thomas Fagan Jr. for the new role of vice president, U.S. Alzheimer’s disease commercial, to help shore up the drug’s launch.
2. SRP-9001
By Ben Adams
Drug: SRP-9001
Companies: Sarepta/Roche
Used for: Gene therapy for Duchenne muscular dystrophy
Est. 2028 sales: $2.2 billion
Drug: SRP-9001
Companies: Sarepta/Roche
Used for: Gene therapy for Duchenne muscular dystrophy
Est. 2028 sales: $2.2 billion
Duchenne muscular dystrophy (DMD) is a devastating disease that takes hold in childhood, slowly weakening the muscles including the heart. The disease, which only affects males, leaves young boys wheelchair-bound and statistically highly unlikely to see their fourth decade.
There remain few drug options for this disease with corticosteroids and physiotherapy becoming the standard therapy over the past few decades. Over the past six years, there have been newer, specific medicines for the condition, with three coming from Sarepta Therapeutics alone, though these have come with questions over their efficacy and indeed whether some should have been approved at all.
The bigger overall issue is that Sarepta’s drugs target a small number of the total patient population. The ultimate goal in DMD treatment is to have a genuinely curative therapy that can help more patients, more widely; that is what Sarepta, alongside drug partner Roche, hopes SRP-9001 can help kick-start.
Unlike Sarepta’s other approved drugs, SRP-9001 works as a gene therapy and is designed to deliver the microdystrophin-encoding gene into muscle tissue to prompt production of the microdystrophin protein. Patients with DMD have a mutation in the DMD gene and can’t make the protein on their own, leading to a progressive loss of muscle strength.
Though it could not be used by all patients, a gene therapy would be a vast improvement on the current drugs on the market. The promise of this therapy area remains high in and of itself as well as for future development, hence its high place on Evaluate’s list.
But despite being second, with estimated 2028 sales of $2.2 billion, Evaluate cautions that U.S. commercial success for SRP-9001 is by no means guaranteed. “Securing full reimbursement in the U.S. is likely to take time, should FDA approvals be won,” the analysts say in their 2023 report, adding this uncertainty “makes it hard to estimate how quickly sales” can be made.
This is especially true for such a new therapy area as “predicting demand is hard owing to lack of precedents and securing reimbursement for what will be a very expensive product is bound to present a problem,” the analysts add in their report. Gene therapy as a marketed treatment is still so new, how to handle it in terms of pricing and regulation will be a new path for everyone.
Questions also remain over this new way of treating DMD, notably on safety, an issue which has dogged gene therapies in the past, as well as its long-term efficacy. These therapies will also be expensive to make and to use, and that will also surely be reflected in their price, with the specter of drug pricing, value and affordability set to rear its head here.
Sarepta is still forging ahead, nabbing a speedy review with the FDA last year, with a Prescription Drug User Fee Act date of May 29, though this could be extended, or even be approved earlier.
And Sarepta is already making big moves to ensure it has the resources to bankroll the launch of SRP-9001, should the FDA give its OK later this year.
The biopharma’s CEO Doug Ingram said in a November interview with Fierce Biotech that the company raised more than a billion dollars during the third quarter “to ensure we have the resources necessary to fully prepare for and successfully launch SRP-9001.”
The company is also changing its commercial, medical affairs, access and reimbursement and patient services teams to prepare for “what could be the most consequential gene therapy launch in history,” Ingram added in the interview.
3. Intravitreal pegcetacoplan
By Ben Adams
Drug: Intravitreal pegcetacoplan
Companies: Apellis
Used for:Complement factor C3 inhibitor for geographic atrophy
Est. 2028 sales: $2billion
Drug: Intravitreal pegcetacoplan
Companies: Apellis
Used for:Complement factor C3 inhibitor for geographic atrophy
Est. 2028 sales: $2billion
Apellis is hoping its tweaked version of pegcetacoplan, the active ingredient in the pharma’s rare disease drug Empaveli, can cross the FDA finish line this year and become the first new drug for the eye disease geographic atrophy (GA).
That would be a big moment, given there are no FDA-approved treatments for the condition, an advanced form of age-related macular degeneration that eventually leads to vision loss and blindness in older people.
There are roughly 1 million Americans living with the condition, and Apellis could be looking at sales of $2 billion by 2028, according to Evaluate, and $3 billion in peak annual sales, a figure Jefferies analysts predicted last year in a note to clients.
However, there is a reason no marketed drugs exist for the condition. Pharma has tried and failed to push GA treatments over the FDA’s finish line in recent years, including an effort by Roche on its complement-inhibiting drug lampalizumab.
Roche’s experimental drug was tipped to top out at $2 billion a year by analysts, but key data from its late-stage trial showed that neither dosing regimen of the complement factor D-binding antibody fragment reduced GA lesion area by significantly more than placebo in the one-year, 936-patient trial. That sounded the death knell for the drug.
Hence, the analysts at Evaluate note there remains much risk here for Apellis, not just from past flops in the industry but from internal issues as well.
Evaluate said Apellis’ progress with its GA project “will be closely watched after the company rattled investors by filing more data with the FDA during the review process,” a decision that pushed back the biotech’s Prescription Drug User Fee Act date by three months to Feb. 26.
Investors were confused by the change in plans, and Apellis’ stock price tanked on the news in the third quarter of 2022. Industry watchers feared that the company might have received some negative feedback from the FDA that prompted the change in plans, though this was never confirmed.
There’s also uncertainty when it comes to the drug’s clinical data. Evaluate adds that as only one of the company’s two phase 3 trials, “a positive outcome is far from assured,” though it still sees a regulatory green light as the most likely outcome.
There’s more uncertainty, too, Evaluate reports. It notes that under normal circumstances, an advisory committee for the drug would have occurred, but, as the FDA’s ophthalmic committee has still not resumed its panel hearings in the wake of COVID-19, “the verdict [is] even harder to call,” as we don’t have the view of its independent review committee.
So, while it takes the final podium place on the top 10 most anticipated drugs list with that meaty $2 billion estimate, that figure is clearly far from guaranteed.
There is also competition on the horizon in the form of Iveric Bio’s C5 agent Zimura, which is tailing close behind, starting its new drug application with the FDA for its GA asset in November last year, meaning if it does nab approval, it will not have the market to itself for long.
Apellis, founded in 2009, is already a commercial drugmaker thanks to pegcetacoplan’s approval last year to treat the rare blood disorder paroxysmal nocturnal hemoglobinuria.
In that field, the drug is marketed as Empaveli and is challenging Alexion’s successful complement inhibitors Soliris and Ultomiris. But the company will need that approval on GA to really boost its sales and make the biopharma a major, blockbuster player in the industry.
4. Donanemab
By Ben Adams
Drug: Donanemab
Companies: Eli Lilly
Used for: Anti-amyloid monoclonal antibody for Alzheimer’s disease
Est. 2028 sales: $1.9 billion
Drug: Donanemab
Companies: Eli Lilly
Used for: Anti-amyloid monoclonal antibody for Alzheimer’s disease
Est. 2028 sales: $1.9 billion
If seeing Eli Lilly’s experimental Alzheimer’s disease drug donanemab on the most anticipated drugs list for 2023 gives you déjà vu, it’s because this drug was in fact on Evaluate’s top 10 list for 2022 as well.
Not only was it on the list, but it topped it last year, being the most anticipated drug to be approved in 2022 with predicted 2026 sales worth a massive $6 billion. How much can change in a year.
Eagle-eye viewers will know that this drug was, of course, not approved as Lilly decided to hold fire on seeking an approval for the drug, coming after the commercial flop of Eisai and Biogen’s Alzheimer’s drug Aduhelm and the regulatory controversy surrounding it clearly promoted a pause for thought from the Big Pharma.
The biggest factor was the Centers for Medicare & Medicaid Services’ decision not to fund Aduhelm for seniors, the predominant market for the drug, with Lilly seeing this as a major risk factor for sales of its own med.
But the Alzheimer’s landscape seems a little less foggy now, helped immensely by the approval of this year’s most anticipated drug. Eisai’s Leqembi works in a similar way to donanemab, bringing out some sun to burn off that fog.
After a few months’ delay, Lilly did send off for an accelerated FDA approval last year and was expectant of an FDA decision this February. All that changed in January, however, when the FDA sent Lilly a complete response letter for its speedy approval of the drug. The FDA said it wants longer data on patients using the drug, and Lilly is now forced to apply for a normal review later this year when its phase 3 data are out.
This will delay any approval until next year and sets it back further behind Eisai and Biogen in the Alzheimer’s market.
Evaluate had already seen the inherent risks here and downgraded its 2022 estimates; that prediction it made last year of $6 billion by 2026 is now $1.9 billion by 2028, a major slash in sales potential. With the complete response letter, those figures will now also surely change.
On top of the delays, donanemab has also had clinical hits and misses, including from its 2021 data which Lilly initially said showed “significant slowing of decline” in Alzheimer’s patients. In reality, the donanemab data were a mixed bag, with a slight win on one disease scale undermined by a failure on a more widely used measure of Alzheimer’s.
The full data showed patients on donanemab experienced a 6.86 decline in scores on the Integrated Alzheimer’s Disease Rating Scale (iADRS). Scores in the placebo group fell 10.06. Lower iADRS scores indicate greater cognitive and functional impairment.
The difference between the iADRS scores was enough for the trial to hit its primary endpoint with a p-value of 0.04, though that was a marginal win, given that it was very close to not being statistically significant.
And it saw a fail on the Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB), a scale commonly used to diagnose dementia due to Alzheimer’s and used in trials for tracing the progression of cognitive impairment in the disease. Here, Lilly found donanemab had no statistically significant effect on CDR-SB over a dummy treatment. These data are certainly no slam dunk for the drug, though the approvals of Aduhelm and now Leqembi may be auspicious for Lilly as the FDA appears willing to allow more drugs through for a disease that remains an unmet medical need.
There was, however, better clinical news for Lilly when it came to a head-to-head trial against Aduhelm. Data published in December last year in a trial comparing the two therapies showed donanemab reduced brain amyloid plaque levels by 65.2% at six months compared to baseline, while Aduhelm reduced levels by just 17% for the same period.
While beating out a drug commercially dead in the water is not the biggest of wins, it still sets Lilly up as the victor and as a strong argument to not just the FDA, but to doctors prescribing the med: If you were worried about the low efficacy of Aduhelm, Lilly now has proof its drug is better, but everyone will now have to wait longer to see whether that can work in the real world. Lilly says it is now planning for a “traditional approval” with the FDA by midyear.
5. RSVPreF3 OA
By Ben Adams
Drug: RSVPreF3 OA
Companies: GSK
Used for: Vaccine for older adults for respiratory syncytial virus
Est. 2028 sales: $1.8 billion
Drug: RSVPreF3 OA
Companies: GSK
Used for: Vaccine for older adults for respiratory syncytial virus
Est. 2028 sales: $1.8 billion
GSK is hoping to gain the first-ever approval for an respiratory syncytial virus (RSV) vaccine this year that could bring in blockbuster sales for the U.K. Big Pharma as it kick-starts a new market for this troublesome respiratory virus.
Cold viruses often don’t get much of a look when it comes to R&D; they are annoyances, but ones that usually make us feel miserable for a few days then clear up.
But some cold viruses can hit vulnerable people much harder, leading to pneumonia and hospitalizations. These are colds caused by RSV, which, in the elderly and in children under 5, can cause serious complications and sometimes be fatal.
There have been several Big Pharma attempts at a vaccine, but the road has been fraught with setbacks and flops. GSK is hoping to change that with RSVPreF3 OA (hopefully the company will come up with a better name this year), and an FDA decision is expected by May 3.
Its vaccine hit the mark in a phase 3 trial in older adults last summer showing that its investigational shot produced statistically significant and clinically meaningful reductions in cases of lower respiratory tract disease caused by RSV in adults aged 60 years and older.
GSK had hoped to develop a vaccine for both infants and those 60 years and older, but a safety concern in its maternal vaccine trial scuppered the plans for the former. But GSK’s CEO, Emma Walmsley, said on a call with journalists last year that “in older adults, [RSV infection] is much more significant to hospitalization than it is for babies,” and therefore she believes that this market will be bigger for any company.
That may well prove the bigger prize. The Centers for Disease Control and Prevention (CDC) estimates that there are up to 120,000 hospitalizations among adults 65 years and older with RSV in the U.S. each year, and up to 10,000 of them die. Among children under 5, the CDC says that there are around 58,000 annual hospitalizations and 100 to 300 deaths.
GSK Chief Commercial Officer Luke Miels told Fierce Pharma in an interview at this year’s J.P. Morgan Healthcare Conference in January that the pharma will initially focus on high-risk individuals for the RSV launch.
There are “a lot of parallels” between RSV and shingles in that vaccine makers need to create an “explained demand” because no RSV preventive solutions were available, he said. GSK hopes RSV vaccines could match the penetration levels seen with flu shots.
Evaluate sees $1.8 billion in sales for the shot in older adults alone by 2028, a highly respectable figure for a new vaccine entrant.
The analysts said in their report, however, that “opinions are divided on the size of the opportunity is respiratory syncytial virus,” an infection it notes that “vaccine makers have finally managed to hit after years of trying.”
That’s because despite likely being first, GSK will almost immediately face a key battle with Pfizer for market share, which is making its own rival RSV vaccine and is not far behind the Big Pharma in the regulatory race to the finish line. It’s Prescription Drug User Fee Act date is also in May, so it will be a photo finish.
Pfizer’s vaccine, PF-06928316, is looking to cater for both older adults and maternal use and having a license for both age groups could help it shore up sales that for now GSK cannot compete with.
Moderna and J&J are also closing in with shots of their own, and Moderna took a bigger step toward a three-way race with Pfizer and GSK in January when it grabbed an FDA breakthrough tag for its phase 3 RSV candidate in older adults. While the latter two pharmas have received priority review status, Moderna is plotting to use a priority review voucher, allowing all three pharmas to cut down their review period by around four months.
But Moderna still remains a little way off its rivals as it plans to file data with the FDA in the first half of this year, meaning it likely will have to wait until late 2023 at the earliest, or more likely early 2024, for an approval.
6. Epcoritamab
By Zoey Becker
Drug: Epcoritamab
Companies:AbbVie and Genmab
Used for: Lymphoma
Est. 2028 sales: $1.7 billion
A bispecific battle over the CD20 bispecific lymphoma market has long been somewhat quietly raging. Come a Prescription Drug User Fee Act date of May 21, the fight will crank up as the FDA decides on AbbVie and Genmab’s epcoritamab.
The CD3xCD20 bispecific antibody seems poised to compete with Roche’s first-in-class Lunsumio, along with a Regeneron candidate, odronextamab. The therapies work by binding to CD20 on malignant B cells and CD3 on T cells to kill cancer cells, bringing CAR-T-like efficacy without the complexity of cell therapies. If approved, epcoritamab can stand apart as the first subcutaneous bispecific antibody approved in the large B-cell lymphoma market.
AbbVie got a piece of the therapy in mid-2020 by handing Genmab $750 million upfront for a stake in epcoritamab and the rest of the company’s pipeline of anti-cancer bispecifics, starting an ongoing oncology collaboration. Under the deal, AbbVie will share commercial responsibilities for the therapy with Genmab in the U.S. and Japan and fly solo for commercialization in the rest of the world, giving Genmab tiered royalties of between 22% and 26%.
Last June, the partners revealed promising results from a phase 2 trial in lymphoma. In 157 patients with relapsed or refractory large B-cell lymphoma, epcoritamab proved an objective response rate of 63% and a complete response rate of 39%.
The median duration of response stood at 12 months. Almost 90% of the complete responders had not relapsed by nine months, meaning that group had yet to reach the median duration of response.
As for safety, 2.5% of participants suffered grade 3 cytokine release syndrome with a median onset of 20 hours post subcutaneous injection and a median resolution time of 48 hours.
Now, the companies are testing subcutaneous epcoritamab across different types of lymphoma. At ASH 2022, the two announced initial results for a combination of epcoritamab plus Rituxan and Bristol Myers Squibb’s Revlimid in newly diagnosed follicular lymphoma, which proved a 90% response rate. Regeneron’s odronextamab is also going after that indication, having bagged an 82% objective response rate in a phase 2 trial. However, Regeneron’s studies have been marred by treatment-emergent adverse events, deaths and dropouts.
As for AbbVie and Genmab’s bids, the two submitted applications to the European Medicines Agency in October for the treatments use in relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy. Thanks to the FDA granting priority review, that agency will decide on epcoritamab’s approval in May.
The Genmab and AbbVie partnership will extend beyond epcoritamab. It gave AbbVie similar commercialization rights to a CD3x5T4 antibody plus another bispecific that targets CD37. Together with epcoritamab, the three are worth up to $1.2 billion for Genmab in clinical and commercial milestones. Even past those three, the two companies will join up in a discovery-stage collaboration to create up to four additional candidates Genmab will take through phase 1.
7. Zuranolone
By Zoey Becker
Drug: Zuranolone
Companies: Biogen and Sage Therapeutics
Used for: Major depressive disorder, postpartum depression
Est. 2028 sales: $1.5 billion
The mental health market is historically filled with gaps in treatment options. Since selective serotonin reuptake inhibitors (SSRIs) hit the market in the 90s, approvals for innovative treatments have been few and far between, leaving a high unmet need for patients with depression disorders.
Enter Biogen and Sage Therapeutics. If approved, zuranolone would be a groundbreaking option for two underserved markets in major depressive disorder (MDD) and postpartum depression (PPD).
The two-week, once-daily therapy would be a first-in-class approval. Targeting the GABA-A receptor, the drug would be a game changer, treating a depressive episode with an “as-needed” short course. While a phase 3 trial of zuranolone in MDD met its main goal of improving depression symptoms over placebo, it missed some secondary endpoints and effects of the drug began to taper off around day 42. But the drug undoubtedly proved its worth in PPD in a phase 3 trial, outperforming placebo on a depression scale at four different time points.
MDD constitutes a huge patient population that’s only gotten larger since the COVID-19 pandemic, with an estimated 17 million Americans experiencing symptoms every year. PPD, while not as large of a market, is no small fish either—in the U.S., an estimated 1 in 8 mothers experience it each year, making up approximately 500,000 cases annually.
Sage claimed the first-ever FDA approval for a PPD treatment in 2019 with Zulresso. While the therapy was a big step in the PPD market, the one-time infusion isn’t as convenient or accessible as zuranolone due to a continuous IV transfusion period of 60 hours. It also carries a black box warning for sudden loss of consciousness and extreme sedation during administration, meaning it must be administered in a restricted distribution program at a certified healthcare facility with close monitoring.
Through Zulresso, Sage was able to “really understand the treatment or the referral patterns in the PPD marketplace itself and establish strong working relationships with patient advocacy groups,” said Chief Business Officer Chris Benecchi at this year’s J.P. Morgan Healthcare Conference.
Zuranolone would fit the bill for an ideal timeline to treat PPD. Currently available treatments can take months to set in, which doesn’t help new mothers and their babies in the crucial bonding weeks.
“When mom’s unwell and can’t attach to the baby, that’s bad for the mom, the baby and [has a] generational impact,” CEO Barry Greene said at the J.P. Morgan Healthcare Conference.
Biogen, for its part, doesn’t have as much of a direct tie to the proposed indications but believes that the treatment would be “highly complementary” to several of its areas of focus, the company said in a statement announcing the partnership. MDD is a common comorbidity in many neurological disorders, including multiple sclerosis, Alzheimer’s disease, spinal muscular atrophy, amyotrophic lateral sclerosis and Parkinson’s disease, all of which Biogen targets.
Zuranolone will likely face approval near the end of the year unless the FDA grants a priority review, which could speed up the decision by four months.
8. Mirikizumab
By Kevin Dunleavy
Drug: Mirikizumab
Companies: Eli Lilly
Used for: Ulcerative colitis, Crohn’s disease
Est. 2028 sales: $1.2 billion
In a phase 3 trial three years ago, mirikizumab established its bona fide by besting Novartis’ Cosentyx in plaque psoriasis.
But Eli Lilly wasn’t satisfied with potentially entering a crowded marketplace, which included two other blockbusters in its IL-23 class—AbbVie’s Skyrizi and Johnson & Johnson’s Tremfya. In addition, Lilly also had a blockbuster in psoriasis with Taltz.
So the company grounded mirikizumab in the indication, opting to investigate its potential in two other autoimmune diseases.
Two years later, Lilly has the monoclonal antibody on the verge of an approval in ulcerative colitis (UC) and is on track for the same in Crohn’s disease in 2025.
With its novel mechanism of action—targeting the p19 subunit of IL-23—mirikizumab has a chance to make a splash as a first-in-class treatment in UC and third in class in Crohn’s disease.
In both indications however, several novel agents are launching (PDF) within the next few of years, making “competition fierce and the market increasingly fragmented,” according to Clarivate’s 2023 Drugs to Watch report.
In UC, for example, Lilly is in a race with more than a dozen candidates now in phase 2b or phase 3 trials, many with promising novel mechanisms of action and new routes of administration, according to analytics company GlobalData.
While numerous agents are currently approved in the indication, GlobalData pharma analyst Garrett Towler believes that therapies in development will soon loom large.
In addition to mirikizumab—which Towler believes will be approved first—he cites the potential of Abivax’s obefazimod and InDex Pharmaceuticals’ cobitolimod. Also in the running are Takeda’s Entyvio along with Skyrizi and Tremfya.
“Becoming the first approved IL-23 inhibitor for this indication will help establish Eli Lilly as a key player in the UC market,” Towler wrote.
Lilly has always had faith in mirikizumab. In 2020, the company was spending $300 million testing it in eight trials spanning the three disease types, according to an estimate from Evaluate Pharma.
Because many patients lose response to biologics, a treatment gap mirikizumab could potentially fill would be sustainable long-term remission. Another is that its alternative mechanism of action could be the answer for patients who are intolerant or resistant to TNF inhibitors such as AbbVie’s Humira or Amgen’s Enbrel.
Mirikizumab proved its efficacy in a trial of 1,281 patients with moderate to severe UC who had not experienced remission with any prior treatments. At Week 12 in the mirikizumab group, 24% of patients were in remission versus 13% in the placebo group.
In addition, while 7% of placebo patients withdrew from the trial because of an adverse event, only 2% of those on mirikizumab did the same.
In the second phase of the trial, involving 544 patients who had a clinical response to mirikizumab in the induction trial, 50% of those on the drug were in remission at Week 52 versus 25% of patients on placebo. Of the 143 patients who had already reached clinical remission at Week 12 in the induction study, 63% maintained it for the rest of the study period.
In its report, Clarivate warns that once on the market for both UC and Crohn’s, mirikizumab could have trouble differentiating itself from other IL-23 inhibitors. Additionally, the launch of biosimilar versions of Stelara, which is scheduled to begin this year, could encroach on the use of all IL-23 inhibitors.
“The data for mirikizumab are very good,” an unidentified gastroenterologist from Italy told Clarivate. “I do not have a preference among all interleukin inhibitors. However, there is preference for (Stelara) because it is already in the clinical practice system.”
9. Etrasimod
By Kevin Dunleavy
Drug: Etrasimod
Companies: Pfizer
Used for: Ulcerative colitis
Est. 2028 sales: $1.2 billion
In March of last year, just three weeks after closing an acquisition of Arena Pharmaceuticals for $6.7 billion, Pfizer reported news that indicated it made a good buy
The key piece of the deal, ulcerative colitis (UC) candidate etrasimod, aced a pair of phase 3 trials, suggesting that the selective sphingosine 1-phosphate (S1P-1) modulator has blockbuster potential.
Scooping up the 25-year-old San Diego biotech with one approved drug—weight loss pill Belviq, which was sidelined by the FDA in 2020 for safety concerns—was a gamble when the deal was struck. At the time, Pfizer didn’t have much to go on—just some blinded data and results from a phase 2 trial. But the company was buying what Arena’s etrasimod UC brain trust, led by Sheldon Sloan, M.D., was selling.
“We got to actually know the team at Arena and what we learned is we really trusted that they knew what they were doing,” Michael Corbo, Pfizer’s chief development officer for inflammation and immunology, told Fierce Pharma in May of last year. “They were a talented group of people not only in drug design, but their ability to design and conduct GI studies.”
In December of 2022, the FDA accepted Pfizer’s new drug application, putting it on track for approval in the second half of 2023. Regulators in Europe have done the same, with a decision expected in the first half of 2024.
The acceptances were based on data from the ELEVATE UC 12 and ELEVATE UC 52 studies, which showed rates of clinical remission at 25% and 32% at 12 and 52 weeks, respectively, in patients with moderate to severe UC, compared to rates of 15% at Week 12 and 6.7% at Week 52 in patients on placebo.
Additionally, in the ELEVATE UC 52 trial, at the 12-week mark, the clinical remission rate for etrasimod patients came in at 27% versus 7.4% for patients on placebo.
The trial utilized a treat-through design which closely mimics real-world clinical practice, Pfizer said. Statistically significant improvements were attained in secondary endpoints, including endoscopic improvement, symptomatic remission, and mucosal healing at weeks 12 and 52, and corticosteroid-free remission and sustained clinical remission at Week 52.
“We believe the treat-through design of the ELEVATE UC 52 study more accurately reflects a real-world treatment approach than the re-randomization design often used in UC clinical trials,” Corbo said.
It could be the start of something big for etrasimod. The once-daily immuno-inflammatory disease treatment also is under investigation for alopecia areata, atopic dermatitis, Crohn’s disease and eosinophilic esophagitis.
The primary competition for etrasimod in UC figures to be Bristol Myers Squibb’s S1P drug Zeposia, which was approved for UC in May of 2021 and is being investigated in the same indications as etrasimod.
While the market is crowded in UC—with treatments such as AbbVie’s Humira—Zeposia and etrasimod figure to have an edge as they are taken in pill form as opposed to being injected. Another oral therapy in the space, Pfizer’s Xeljanz, is under scrutiny as drugs in its JAK inhibitor class face safety concerns.
10. Sotatercept
By Kevin Dunleavy
Drug: Sotatercept
Companies: Merck
Used for: Pulmonary arterial hypertension
Est. 2028 sales: $1 billion
The pièce de resistance of Merck’s $11.5 billion deal to acquire Acceleron in 2021 was sotatercept, which could finally be the disease-modifying breakthrough needed in pulmonary arterial hypertension (PAH).
Sotatercept, a first-in-class fusion protein, was targeted by Merck in its effort to diversify from immuno-oncology and its superstar cancer treatment Keytruda. So far, so good, as positive top-line data released from a phase 3 trial in October 2022 have promoted analysts to peg sotatercept’s peak sales at $2 billion.
Sotatercept is an add-on therapy to standard of care treatment. With its novel mechanism of action, targeting BMPR-II signaling, sotatercept could potentially address the underlying cause of PAH as opposed to current therapies that simply target symptoms by dilating blood vessels. While current therapies offer relief, they are not curative.
Also adding to sotatercept’s value is that it is injected under the skin.
“All of those factors are unique to sotatercept,” CEO Rob Davis said upon inking the Acceleron deal. “There are no other drugs in development that’s that same profile either within Merck or outside.”
Merck’s heart disease offerings are relatively thin, though the company has a history of success in the area. Cholesterol-reducing drugs Vytorin and Zetia made a combined $3.7 billion in 2016 before they were overrun by generic competition.
In the registrational STELLAR trial of 324 patients, those on sotatercept showed improvement in a six-minute walk test over those on placebo at 24 weeks. Sotatercept patients also saw statistically significant improvements in eight of nine secondary measures.
“The results from the secondary efficacy outcomes, including a favorable benefit seen in patients’ time to a clinical-worsening event, are especially noteworthy,” Dean Li, M.D., Ph.D., Merck’s Research Laboratories head, said in a release. “The results observed in the Stellar study suggest that sotatercept has the potential to transform the treatment of patients with PAH.”
The condition results when high blood pressure in the arteries of the lungs causes difficulty in breathing and walking. If left untreated it can lead to heart failure. In idiopathic PAH, the cause of the disease is unknown. Heritable PAH is acquired genetically, while associated PAH comes from other conditions such as sickle cell disease, HIV, lupus or congenital heart disease.
Merck expects to file for approval in early 2023 with a potential launch late in the year. Two other trials are underway for sotatercept, which has received fast-track and breakthrough designations.
A potential stumbling block for sotatercept is its arduous administration regimen, starting with five subcutaneous doses every 21 days.
Originally approved in 2009, Tyvaso is gaining steam thanks to an April 2021 blessing from the FDA for pulmonary hypertension associated with lung disease. Then, last May, United won another nod for an inhaled dry powder version of Tyvaso.
Originally published in Fierce Pharma.
