Mizuho Bank Ltd.

In the first quarter, sales of the top three products Amgen gained from its $27.8 billion acquisition of Horizon Therapeutics fell far short of analyst expectations, with each seeing a double-digit sequential sales decline. It’s been 19 months since Amgen completed its $27.8 billion acquisition of Horizon Therapeutics, and the California company is still struggling to build momentum for three of the prized possessions of the deal—rare disease drugs Uplizna, Krystexxa and Tepezza.When Amgen presented its first-quarter earnings Thursday, none of the trio met analyst expectations. With sales of $91 million, Uplizna came up $20 million short of the consensus projection. Meanwhile, Krystexxa’s haul of $236 million was $57 million shy of expectations, and Tepezza’s $381 million figure was $69 million off the mark.The shortfall for the Horizon products came during a quarter in which most of the company’s other treatments exceeded expectations. In fact, Amgen’s overall revenue of $8.1 billion was a 9% increase year over year and topped the analyst consensus. The lack of success for the Horizon drugs is apparently becoming a sore subject for Amgen execs. During a conference call, after an analyst asked about the stagnant sales of Tepezza and referred to a “couple years” since the Horizon buyout, Chief Financial Officer Peter Griffith was quick to make a correction.“Just a reminder that the transaction closed in October of 2023,” Griffith said. “It’s been about a year and a half, although so much has happened in the world it might feel like more than that.”The most vexing Horizon product has been with Tepezza, which remains the lone drug on the market for thyroid eye disease. In its second full year on the market under Horizon, in 2022, it generated $1.96 billion in revenue. But, in the following year, sales came in at $1.77 billion, followed by $1.85 billion last year, when there were signs that Tepezza was rallying.But the $381 million quarterly result for the treatment was a stunner—it’s lowest figure for a three-month period since the first quarter of 2021 and a 17% sequential decline.“Sales of Tepezza and Krystexxa were adversely impacted in the quarter by changes to U.S. wholesaler inventory levels," Amgen’s chief commercial officer Murdo Gordon explained. "We do not expect similar deductions in inventory levels for the remainder of the year."But the result sounded an alarm bell with Mizuho Securities analyst Salim Syed, who noted the 9% decline in volume and 8% decrease in inventory levels, which “likely put the Horizon acquisition into even more question,” he wrote in a note to investors.Gordon explained that the initial uptake of Tepezza was strong as it was a long-awaited answer for people who had serious cases of the eye disease and were readily prescribed the treatment from plastic surgeons. To grow sales, Tepezza needs to secure more prescriptions from general ophthalmologist and endocrinologists, he added.But tapping this segment of the market “may be more challenging to penetrate than previously communicated by the company,” analysts from Citi wrote in a note to clients.Amgen is far from abandoning hope for Tepezza. The company recently gained a thumbs-up from Europe’s Committee for Medicinal Products for Human Use nd is ready to launch there upon an expected approval. An additional edge Amgen could secure to help spur sales would be to earn approval for a subcutaneous version of Tepezza, as opposed to the 60- to 90-minute infusions patients undergo every three weeks as it stands. A subQ option would allow patients to receive the treatment faster and in many more settings than at infusion centers. Testing on the formulation began last year.On a much smaller scale, sales also were disappointing for Uplizna, which fell sequentially from $101 million in the fourth quarter to $91 million in the first.But help has already arrived in the form of a label expansion last month, making Uplizna the first drug to win an FDA approval for immunoglobulin G4-related disease (IgG4-RD), a disease that affects 20,000 patients in the U.S. and has no standard of care. Additionally, Amgen announced Thursday that it has secured an FDA decision date of Dec. 14 for Uplizna to treat patients with generalized myasthenia gravis (gMG).With respect to all of the Horizon products, Amgen’s message on Thursday was to give them more time.“It’s a very young portfolio of products where we’re really just beginning to address the severe diseases that these drugs treat,” Jay Bradner, Amgen’s R&D chief, said. “Whether it’s Tepezza, Uplizna, Krystexxa or Tavneos, these are going to be key growth-driving products for us over the long haul.”   

Dive Brief:Bristol Myers Squibb on Monday said its drug Camzyos failed a Phase 3 trial in people with a progressive heart condition, closing off an opportunity to expand use of a medicine it sees as a future blockbuster.According to Bristol Myers, Camzyos missed the dual main goals of a study focused on the non-obstructive form of HCM, or hypertrophic cardiomyopathy. It failed to meaningfully improve peak oxygen consumption as well as scores on an assessment of heart health. The company didnt provide study details, but said more information will be shared with the scientific community in the future.Camzyos was acquired through the $13 billion buyout of MyoKardia in 2020 and two years later became the first drug cleared for use in the obstructive and more common form of the disease. Biotechnology companies Cytokinetics and Edgewise Therapeutics are developing similar medicines that are both in the advanced stages of clinical testing. Cytokinetics drug, aficamten, could be approved in the U.S. later this year.Dive Insight:Camzyos setback carries implications for Bristol Myers as well as the companies trying to develop better medicines for HCM, a chronic condition characterized by a potentially deadly stiffening of the heart muscle.Bristol Myers is bracing for the losses of billions of dollars in yearly revenue when the patents expire for its cancer immunotherapy Opdivo and blood thinner Eliquis. The company already announced a cost-cutting plan under CEO Chris Boerner, and is looking to a handful of medicines, Camzyos among them, to grow sales in the years ahead.Camzyos generated $602 million in sales in 2024. But Bristol Myers has said that number could reach $4 billion in 2029, and one way to get there was a clearance in the non-obstructive setting, which is estimated to account for about a third of the people with the condition. The setback is a disappointment, wrote Leerink Partners analyst David Risinger, though Bristol Myers could rebound if a series of coming Phase 3 readouts are successful.The study failure also stirred debate among analysts as to whether drugs like Camzyos, known as cardiac myosin inhibitors, can help all people with HCM. Camzyos has proven beneficial for the obstructive form that impedes blood flow and can lead to heart failure as well as other potentially serious complications. The non-obstructive type doesnt, but can still put people at risk of poor health outcomes. The new study tested whether Camzyos might be similarly helpful for those people as well.The fact that Camzyos wasnt suggests obstructive and non-obstructive HCM are two unique diseases, said Milind Desai, the director of the Cleveland Clinics HCM Center, in a statement provided by Bristol Myers.Analysts were mixed on whether the cardiac myosin inhibitors Cytokinetics and Edgewise are developing might similarly struggle in non-obstructive HCM. Cytokinetics drug, aficamten, is under Food and Drug Administration review in obstructive HCM and in a Phase 3 trial in non-obstructive disease. Edgewises EDG-7500 could join it in late-stage testing next year.Matt Phipps, of the investment bank William Blair, wrote that Camzyos shaky performance in the latest study as well as Phase 2 testing in non-obstructive HCM patients may be more attributed to disease biology, which has negative implications for the whole drug class.That form of the disease is also more heterogeneous, making it tougher for a drug to succeed in testing, added RBC Capital Markets Leonid Timashev.Still, there are key differences between the drugs and their development plans that leave some analysts optimistic about Cytokinetics and Edgewises chances. Aficamten appeared to perform better in earlier testing in non-obstructive patients, and Cytokinetics Phase 3 study is designed differently, wrote Mizuho Securities Salim Syed. RBCs Timashev added that EDG-7500s unique mechanism could overcome the limitations of other medicines in non-obstructive HCM.We now see a 2-handed market split between Cytokinetics and Edgewise, Timashev wrote. '

After the death of a 16-year-old patient, Sarepta and Roche have temporarily paused three trials in Europe of their Duchenne muscular dystrophy gene therapy Elevidys. In response to a request from the European Medicines Agency (EMA) following the death of a 16-year-old patient in the U.S., Sarepta and Roche have temporarily halted three clinical trials in Europe of their Duchenne muscular dystrophy (DMD) gene therapy Elevidys.In a March 31 letter (PDF) from Roche to the World Duchenne Organization, the Swiss drugmaker said that the companies are pausing enrollment and dosing in the studies while continuing to monitor already-enrolled participants and collect data.The paused trials include the Sarepta-sponsored phase 3 Envision study, which is evaluating Elevidys in boys aged 8 to 17; Roche’s phase 2 Envol study, which is investigating Elevidys in babies and newborns; and Sarepta’s Study 104, a phase 1 look at Elevidys in boys ages 4 to 9 with pre-existing antibodies to a particular serotype.The trials have been halted in all EU countries, and the Envol study has been paused in the U.K. The trials are on hold until “analysis into the cause of death is complete,” Roche wrote. Meanwhile, four other U.S.-based Elevidys studies remain ongoing.“While any clinical hold is concerning, we believe the EMA's request to pause the 3 Elevidys studies will likely be temporary and unlikely materially delay their completion timelines or the EMA review of Elevidys' marketing authorization application (MAA),” analysts from Mizuho Securities wrote in a note to investors.In an update on Friday, April 4, Sarepta said that an independent data monitoring committee (DMC) met and concluded that "based on the totality of evidence, the overall benefit-risk profile remains favorable to continue dosing in the paused clinical trials without changes to the study protocols."Sarepta and Roche plan to submit the DMC's findings to EU regulators "within a week" for review.  Two weeks ago, Sarepta disclosed the patient’s death, which was attributed to acute liver failure. Serious liver injury is a known safety risk of Elevidys.“We cannot rule out the possibility that Elevidys was a contributing factor,” a Sarepta spokesperson told Fierce Pharma last month.The incident brought increased attention to the safety of gene therapies that use adeno-associated viruses (AAVs) as vectors to deliver therapeutic genes. In Elevidys’ case, the administered gene produces microdystrophin, a shortened version of the normal dystrophin protein that’s missing in Duchenne patients.In 2022, Novartis recorded two deaths for its AAV-based, spinal muscular atrophy gene therapy Zolgensma.Although it is not a new safety signal, acute liver failure leading to death is a severity of the disorder not previously reported for Elevidys, which has been provided to more than 800 patients, Sarepta said. The company also reported that testing revealed the deceased patient had a recent cytomegalovirus infection that was identified by his treating physician as a possible contributing factor.Since the report of the patient death, Sarepta’s share price has dropped by 42%.“This is yet another unfortunate development for a story that cannot seem to catch a break,” Leerink wrote on Wednesday, adding that the weight of a 16-year-old patient likely means that he was provided a higher dose than the average Elevidys recipient.“We acknowledge that such severe side effects associated with mortality can certainly be alarming and cause the community to question the risk/benefit of treating older patients. However, we believe that the very low overall incidence is encouraging,” Leerink wrote, adding that its projection of the likelihood of an EU approval remains unchanged at 60%. Elevidys was approved on an accelerated basis in the U.S. in June of 2023 for boys ages 4 and 5. In June of last year, the FDA expanded its label to include all DMD patients aged 4 and up.Both FDA nods stirred controversy, as neither was based on a trial that met its primary endpoint. During development of the treatment, trials were halted in 2018 and 2021 because of safety concerns. Also drawing ire was the $3.2 million price tag for the one-time treatment.Still, sales have scaled up quickly, indicating the unmet need in the indication. In the fourth quarter, Sarepta reported revenue of $383 million from Elevidys, which was a 110% increase from the previous quarter. Leerink Partners projects Elevidys sales to reach $2 billion this year.Editor's note: This story was updated at 9 a.m. EDT on Friday, April 4, to include the latest information from Sarepta.