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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
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.
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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.
By Ben Adams
2. SRP-9001
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.
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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
Drug: Intravitreal pegcetacoplan
Company: Apellis
Used for: Complement factor C3 inhibitor for geographic atrophy
Est. 2028 sales: $2 billion
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.
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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.
By Ben Adams
4. Donanemab
Drug: Donanemab
Company: 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.
By Ben Adams
5. RSVPreF3 OA
Drug: RSVPreF3 OA
Company: 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.
