Rozanolixizumab

Aside from entrenched rivals like AstraZeneca’s Ultomiris, Vyvgart is now facing pressure from a pair of myasthenia gravis biologics newcomers introduced by UCB. As argenx continues to scoop up biologics market share with its antibody fragment Vyvgart in generalized myasthenia gravis (gMG), the Dutch immunology outfit is confident that it’s “just at the beginning of the growth curve” in its inaugural indication, executives said on an analyst call Thursday. Not content to rest on its laurels, either, argenx is leveraging the commercial insights it’s garnered over the past two years as it preps for the launch of Vyvgart’s next potential approval in chronic inflammatory demyelinating polyneuropathy (CIDP), slated for an FDA decision by June 21. Argenx this morning reported 83% year-over-year and 6% quarter-over-quarter revenue growth to $398 million in the first three months of 2024. The autoimmune company’s sales currently hinge on Vyvgart and the drug’s Halozyme-partnered subcutaneous formulation Vyvgart Hytrulo, both of which are approved in gMG in the U.S. and many other countries. Vyvgart also boasts a single approval for the rare bleeding disorder immune thrombocytopenia (ITP) in Japan. The company’s sales growth this quarter reflects the “strong medical need in myasthenia gravis,” as well as the “quality” of Vyvgart and the “excellent execution” of the drug’s commercial rollout, analysts with ODDO BHF wrote in a note to clients Thursday. The analysts stuck by their thesis that the products remain well positioned to hit peak sales of $11 billion in 2035—an estimate that accounts for future indications like CIDP, too. Aside from the opportunities in gMG and CIDP, argenx also aims to broaden Vyvgart’s reach with the introduction of a prefilled syringe. The company said in an earnings release that it’s on track to submit a U.S. application for that delivery format in 2024’s second quarter. Still, Vyvgart is far from the only gMG biologic in town. Aside from entrenched rivals like AstraZeneca’s Ultomiris, Vyvgart is now facing pressure from a pair of newcomers introduced by UCB. UCB won back-to-back nods for two separate gMG therapies last year, starting with a green light for its subcutaneous monoclonal antibody Rystiggo in July. In October, the company’s med Zilbrysq—a targeted C5 inhibitor with a different mechanism of action than Rystiggo—snared FDA backing as the first subcutaneous gMG-targeted therapy patients can administer themselves, according to UCB. But despite those new challengers, argenx’s chief operating officer, Karen Massey, said the company isn’t seeing a significant impact from competition.  In fact, argenx continues to see Vyvgart’s market share grow quarter over quarter among biologics, she said during the call. She credited much of that growth to the product’s subcutaneous version, which saw a 34% uptick in U.S. patients this quarter. Massey said the company continues to see many new patient starts on Vyvgart, with more than 50% of those novel prescriptions coming from people who are switching over from an oral gMG therapy. “I think the more innovation that comes to market, the more the biologic share overall is going to grow and the more we’ll be able to help lead within that biologic share,” Massey said. “I’m very confident that we’re just at the beginning of the growth curve with MG,” the COO added. Building on Massey’s point, argenx CEO Tim Van Hauwermeiren noted on the company’s call that argenx recently kicked off a Vyvgart study in seronegative myasthenia gravis as well, which has the potential to become a label-expanding study. Roughly 15% of gMG patients are estimated to be seronegative, which could provide a meaningful addition to the drug’s current green light, the CEO said. All told, there are now more than 10,000 gMG patients on argenx’s treatment globally, the company noted (PDF) in a slide deck accompanying its earnings presentation. As for Vyvgart’s upcoming opportunity in CIDP, argenx has been busy establishing a “comprehensive launch plan” to help educate both neurologists and patients around the benefits of switching over to the med, Massey said. With the CIDP therapies on tap today—typically steroids and intravenous immunoglobulin—roughly 88% of patients still experience residual symptoms despite ongoing treatment, argenx’s research has shown. Given the drug’s successful phase 3 trial in CIDP last month and its clean safety profile, argenx figures patients and doctors will be enticed to make the switch to Vyvgart because they won’t “have to balance that trade-off between efficacy and treatment burden,” Massey said. Argenx plans to adopt the same pricing approach it used in gMG for Vyvgart’s potential green light in CIDP, including through value-based arrangements with payers, Massey said, noting access talks for that potential launch are “on track.” Since its commercial debut in late 2021, argenx has touted the potential for Vyvgart as a pipeline in a product. But while Vyvgart is faring well in many disease areas, the drug has shown its limitations in recent months, too. Alongside earnings Thursday, argenx revealed that it’s discontinuing planned development of the FcRn inhibitor in ANCA-associated vasculitis, which describes a group of rare autoimmune diseases marked by inflammation and damage to the small blood vessels. The decision comes after a risk assessment of ongoing studies following recent clinical misfires in ITP and the chronic blistering disease pemphigus.

Several factors come into play to dull orphan drugs' shine such as the “blazing return of big drugs for big diseases,” according to Evaluate. The orphan drug sector has long been clearing growth in the larger pharmaceutical market with booming sales. But, thanks to blockbuster meds across wider disease areas and other challenges, the lucrative market may soon slow down for the first time in years. According to Evaluate’s 2024 report, “Orphan Drugs are Losing Their Sparkle,” the category is set to pick up $185 billion this year and some $270 billion by 2028. Yet, sales growth is notably shrinking. The meds averaged an almost 11% sales increase in the decade ending in 2023 but will "barely hit double digits" through 2030.  Several factors come into play to dull orphan drugs' shine, such as the “blazing return of big drugs for big diseases,” according to Evaluate. While the obesity market is currently the hottest ticket, blockbusters across disease areas such as neuroscience, immunology and oncology also stand to overtake orphan drug’s slice of the pie. Plus, there are pricing pressures stemming from the high price tag on orphan drugs. Payers are “more discerning” as of late and aren’t as keen to cover the steep prices, favoring more widespread disease areas instead, according to Evaluate.  Still, the sales slowdown is “relative,” head of thought leadership at Evaluate Daniel Chancellor said in a press release. “As the overall prescription drug market continues to grow, so will that for rare diseases.” 2028's top orphan drugs   According to the report, the top 10 most valuable orphan drugs will together collect more than $57 billion in 2028. That top 10 list has had a bit of a shakeup since Evaluate’s last ranking in 2023, largely due to increasing competition and the Inflation Reduction Act. Johnson & Johnson’s multiple myeloma blockbuster Darzalex, Vertex’s cystic fibrosis med Trikafta and Roche’s hemophilia A therapy Hemlibra all kept their top three slots on Evaluate’s list of the 10 top sellers by 2028 in worldwide sales with predicted respective revenues of $17 billion, $8.7 billion and $6.2 billion. However, AbbVie’s popular cancer med Imbruvica has fallen out of the top 10 thanks to Beigene’s rival BTK inhibitor Brukinsa and AstraZeneca’s Calquence. While Calquence is slated for $4 billion in 2028 sales and Brukinsa should pick up $3.8 billion, AZ’s offering fell from fifth place to seventh over the past year. Argenx’s Vyvgart also slipped, dropping to 14th place with a forecast $3 billion in 2028. The generalized myasthenia gravis drug is challenged by growing competition such as UCB’s two new treatment options, Zilbrysq and Rystiggo, plus upcoming threats from Johnson & Johnson’s nipocalimab. Despite label expansions last year, Roche’s spinal muscular atrophy therapy Evrysdi had a similar story with competition from Biogen's Spinraza and Novartis' Zolgensma. Meanwhile, new entrants to the top 10 list included Incyte and Novartis’ JAK inhibitor Jakafi, which placed sixth with a 2028 sales expectation of $4.2 billion, and J&J’s Carvykti. The latter is the only CAR-T therapy to appear on the top 10 list with $4.4 billion in predicted 2028 sales. As for the wider 2028 picture, Amgen swiped AbbVie’s spot on the list of the top 10 companies with largest orphan drug sales. That can be attributed to Amgen’s $27.8 billion acquisition of rare disease drugmaker Horizon Therapeutics, which brings orphan drugs Tepezza, Krystexxa and Uplizna into the fold. The top spots in that ranking go to J&J, Roche and AZ, with J&J taking No. 1 in a landslide. The company is expected to bring in over $30 billion in 2028 orphan drug sales, while Roche at No. 2 looks to take home $16.8 billion.