Seven Potential Blockbuster Approvals To Look Out For In 2023
Executive Summary
After highlighting oncology drugs pegged to make a splash next year with the help of Biomedtracker, Scrip takes a look at seven potential blockbusters across a range of therapeutic areas including neurology, dermatology and blood disorders slated for approval next year.
Eisai Takes Shot At Alzheimer’s With Lecanemab
Kicking off the list are three anti-amyloid antibody candidates vying to become an effective new treatment for for Alzheimer’s disease (AD) following the commercial failure of Biogen, Inc.’s Aduhelm (aducanumab). They are led by Eisai Co., Ltd. and Biogen’s lecanemab for which the firms have initiated a rolling biologics license application with the US Food and Drug Administration based on findings from a Phase IIb trial in 856 participants with early AD.
The trial showed lecanemab reduced brain amyloid by a mean of 0.306 SUVr units with more than 80% of subjects becoming amyloid negative by visual read at 18 months. Amyloid-beta builds up in deposits in the extracellular space in the brain, disrupting key functions and leading to the neuronal degeneration typical of AD.
Eisai claims lecanemab is differentiated from other amyloid-targeting drugs, such Aduhelm, because it is selective for more soluble protofibrils over insoluble fibrils and plaques. Indeed, the drug candidate has shown more modest rates of brain swelling when compared with Aduhelm, which has been plagued with safety concerns since its commercial launch. (Also see "How Biogen’s Aduhelm Bet Became A Commercial Bust" - Scrip, 6 Jun, 2022.)
The FDA has set a January deadline for a decision on lecanemab, which is expected to capitalize on the precedent set by Aduhelm while bypassing regulatory mistakes and controversies associated with the latter drug. The Biomedtracker analysts noted the asset could become the first drug of its class to win a full approval in AD based on the outcome of an ongoing Phase III trial, which is set to read out at the end of the month.
RBC Capital Markets analysts project lecanemab could make $48m during its first year on market with peak sales potential of more than $2.05bn by 2031.
Lilly’s Donanemab Could Boast Payer Advantage
Hot on Biogen’s heels is rival Eli Lilly and Company’s donanemab, which is directed at the pyroglutamate modification of the third amino acid of the amyloid beta epitope. This contrasts with Aduhelm and lecanemab, which target the beta-amyloid peptide epitope formed by N-terminal amino acids.
The difference means that donanemab treatment can be stopped after patients show clearing of amyloid plaques, which could prove advantageous for payers. Lilly has initiated a rolling BLA based on data from donanemab’s Phase II trial in which 80% of treated patients were amyloid negative after 18 months.
Lilly also anticipates a readout next year of its Phase III donanemab trial, having deprioritized prior plans for an accelerated approval. (Also see "Lilly Waiting On Phase III Data For Donanemab" - Scrip, 3 Feb, 2022.) Analyst projections of donanemab peak sales last year had been as high as $10bn but they are now more modest, sitting at around the $6bn mark.
Roche Touts Gantenerumab’s At-Home Potential
Further behind in the clinic is Roche Holding AG’s gantenerumab, which has faced several setbacks in its development including two failed late-stage trials in very early and pre-symptomatic stages of AD. Nonetheless, the major is determined to forge ahead in early AD where gantenerumab is under investigation in the pivotal GRADUATE program, set to read at out in the fourth quarter. (Also see "Roche Deals With Huge Gantenerumab Curiosity At H1 Update" - Scrip, 23 Jul, 2021.)
In addition to the N-terminal amino acids targeted by Aduhelm and lecanemab, Roche’s candidate is also directed at the central beta-amyloid amino acids and thus requires the beta-amyloid peptide to be folded. The firm hopes gantenerumab could be administered at home by patients or caregivers, thereby enabling coverage under Medicare Part D.
By contrast, gantenerumab’s rivals require physician-supervised administration and would fall under Medicare Part B. Analyst consensus places peak gantenerumab sales at $3bn. (Also see "Readouts For TIGIT And Alzheimer’s Drugs Will Define Roche’s Year" - Scrip, 3 Feb, 2022.)
CSL To Advance First Hemophilia B Gene Therapy
Elsewhere, several gene therapy candidates in the hemophilia space are set to make their debut next year, starting with CSL Limited and partner uniQure N.V.’s EtranaDez (etranacogene dezaparvovec) for hemophilia B.
The adeno-associated virus A5 (AAV5)-based treatment has been filed in both the US and EU on the back of data from the Phase III HOPE-B trial in which EtranaDez reduced the adjusted annualized bleed rate (ABR) by 64% and proved superior to prophylaxis treatment at 18 months post-treatment compared with a six-month run-in period. The drug is designed to restore near-normal blood-clotting ability in patients by addressing the faulty F9 gene that causes clotting Factor IX deficiency, thereby addressing the root cause of the condition.
Notably, EtranaDez was one of several pipeline candidates that saw a six-month delay to its projected launch date after the FDA last year raised the bar for hemophilia gene therapy approvals to include one-year follow-up data from the point of Factor IX stabilization. The drug’s long-term data showed a 2.5% reduction in Factor IX activity over six months, although bleeds remained rare.
EtranaDez is set to win approval at the end of the year which means it could benefit from launching a year before Pfizer Inc.’s rival asset, fidanacogene elaparvovec. H.C. Wainwright analysts last year projected CSL’s drug would take a decent chunk of the hemophilia B market, which is projected to reach $40bn in value over the next 15 years. (Also see "uniQure/CSL’s EtranaDez Could Take Lead Position In Hemophilia B Gene Therapy Market" - Scrip, 9 Dec, 2021.)
BioMarin Overcomes Roctavian’s Hemophilia B Delay
Meanwhile, BioMarin Pharmaceutical Inc.’s Roctavian (valoctocogene roxaparvovec) is the one to watch for hemophilia A, which is more common than hemophilia B and affects an estimated 20,000 people in the US.
BioMarin has faced a bumpy ride with Roctavian, which initially received a complete response letter from the FDA after a 2020 filing. The US regulator had requested two-year follow-up data from BioMarin’s pivotal study, even though the trial had established that Roctavian reduced ABR by 84%. The firm is expected to resubmit to the FDA this month and the drug should enter the market next year. (Also see "BioMarin Gears Up To Give Roctavian Another Go" - Scrip, 13 Jan, 2022.)
Last month, Roctavian won a conditional marketing approval from the European Commission which bodes well for US prospects. (Also see "New EU Approvals" - Pink Sheet, 30 Aug, 2022.) The drug should have a head start on rival Pfizer Inc.’s candidate, giroctocogene fitelparvovec, which has yet to resume its pivotal trial after the FDA lifted a clinical hold placed on it due to high levels of Factor VIII expression. Morningstar analyst Karen Andersen projects peak Roctavian sales of around $1bn.
J&J To Address Hypertension Unmet Need
In the cardiovascular space, Johnson & Johnson and partner Idorsia Ltd. are planning to submit a US filing for their systemic hypertension candidate, aprocitentan, towards the end of the year. The major estimates that 10-20% of people with hypertension are resistant to standard of care treatment, posing a significant unmet need that aprocitentan could help address.
The endothelin receptor antagonist (ERA) prevents endothelin-1 from binding to the ETA and ETB receptors, a process known to trigger neurohormonal activation, vascular hypertrophy and endothelial dysfunction. Data from an aprocitentan pivotal trial showed the drug significantly reduced blood pressure in patients with hypertension that was uncontrolled despite having taken at least three medications.
In keeping with its broader drug class, aprocitentan was also associated with edema in 30% of patients. J&J nonetheless remains confident about the risk-benefit profile and has highlighted that an ageing population only increases the need for another treatment option.
Jefferies analyst Rosie Turner last month projected peak aprocitentan sales of at least $2.4bn. However, other observers remain skeptical of the drug’s commercial prospects, citing a highly genericized hypertension market and lack of clarity on launch plans as potential roadblocks. (Also see "Idorsia And J&J Hypertension Drug Edges Closer To An Uncertain Market" - Scrip, 24 May, 2022.)
Lilly Aims To Challenge Dupixent’s Market Dominance
Lastly, in the dermatology arena, Eli Lilly and partner Almirall SA’s lebrikizumab for atopic dermatitis could bring competition for Sanofi’s mega-blockbuster Dupixent (dupilumab) following US and EU filings planned for the end of the year.
Lebrikizumab is an IL-13 receptor inhibitor whereas Dupixent inhibits both IL-13 and IL-14. While inhibiting IL-13 alone has an efficacy benefit in treating atopic dermatitis, the approach does not appear to reduce the risk of developing conjunctivitis that is seen with dual-cytokine inhibitors such Dupixent. Furthermore, the Biomedtracker analysts remarked that dermatologists’ familiarity with Dupixent mean it could continue to be used as the first-line biologic of choice for some time.
However, the option of a once-monthly maintenance dose for lebrikizumab could give it an edge over Dupixent. In its pivotal trial, treatment with Lilly’s candidate produced clear or almost clear skin at 16 weeks in 33% of patients compared with just 11% if patients on placebo.