Bristol Myers Squibb’s clotbuster Eliquis is set to be this year’s biggest selling cardiac drug, Evaluate Pharma consensus forecasts suggest – and remarkably, it is forecast to retain the crown all the way to 2028. This comes courtesy of several court rulings preventing US generic competition until that year. Indeed the remarkable aspect of the top 10 drugs lists is the longevity of these products. Lipitor, only just dethroned by Keytruda as the bestselling drug of all time, was first launched in 1997 and is still bringing in swathes of cash for the generics business Viatris; Roche’s stroke therapy Activase is a decade older. Only two drugs not yet launched appear in the 2028 table: Cytokinetics’ cardiomyopathy project aficamten, due a pivotal readout this year, and Merck’s sotatercept, which already has highly positive pivotal data in pulmonary arterial hypertension. As for the leading companies, Novartis takes the current top spot buoyed by heart failure therapy Entresto; in 2028 it will also benefit from the PCSK9 Leqvio, though this will not make up for the sales shed by Entresto. All but one of this year’s top 10 companies will see their heart drug sales fall in the next five years. The exception is United Therapeutics, whose inhaled pulmonary arterial hypertension therapy Tyvaso is growing fast.

Keytruda is the gift that keeps on giving, with the PD-1 checkpoint inhibitor smashing expectations in Merck & Co’s second-quarter earnings; global sales surged 19% to $6.3bn. Merck also reported unexpectedly high sales of the HPV vaccine Gardasil, as huge demand in China pushed sales up by 47% to $2.5bn. Merck added a billion to its full-year sales guidance, taking it to $58.6-59.6bn, and shares in the group responded accordingly, rising 2% this morning before flattening. Merck put Keytruda’s success in the quarter down to strong sales in earlier treatment lines, including in triple-negative breast cancer. The results further emphasise Merck’s reliance on Keytruda’s income stream, which could start drying up in the next decade through patent expiries. Merck has already announced a string of acquisitions in the hopes of finding replacement revenues, including the $10.8bn takeover of Prometheus earlier this year. On today’s conference call, chief exec Robert Davis said the group was “out actively looking” and would use its firepower to drive deals. But with earnings per share in the quarter dragged down by the Prometheus buyout Merck will need to be mindful of overpaying for assets.

Yesterday Biomarin confirmed what many had suspected: the company has yet to treat any patients with its haemophilia A gene therapy Roctavian. In the US, this is understandable, since the product only received an FDA nod in June. But it has been approved in Europe for almost a year. Biomarin did stick to its full-year Roctavian sales guidance of $50-150m, but if it is relying on the US market time could be tight – the group said it could take two to five months from initial interest to treatment. Biomarin added that it would only need to treat 50 US patients this year to hit the mid-point of its guidance. Meanwhile, the first German patient could be treated in late August, and negotiations are ongoing with payers in France and Italy. With scepticism around the Roctavian launch, at least the group’s achondroplasia therapy Voxzogo is picking up the slack, with second-quarter sales of $113m beating consensus of $96m. However, during a conference call yesterday Biomarin flagged supply constraints with this product. With these issues vexing investors, the group’s stock fell 3% in early trade. 

Eisai and Biogen’s Leqembi received full approval to treat Alzheimer’s disease last month. That was expected; what was not was that the label came with a boxed warning over Aria, a brain swelling disorder, with recommendation for ApoE4 genetic testing to assess Aria risk. Leqembi’s launch is under way with Biogen highlighting on its quarterly call that it has Medicaid coverage in 48 states so far. Elsewhere good news finally came for Verrica’s Ycanth after three previous complete response letters. This is the first FDA-approved therapy to treat molluscum contagiosum, a viral condition that creates a localised skin infection. There was also good news for Astrazeneca and Sanofi’s Beyfortus, an antibody to prevent respiratory syncytial virus (RSV) in young children. Sanofi noted on its second-quarter call that it is confident of a broad recommendation at the ACIP meeting on 3 August, and will price the therapy like a premium vaccine. Hot on its heels is Pfizer’s Abrysvo, due a Pdufa decision as a maternal RSV vaccine later this month.

Earlier this month, a report of six cases of severe eye inflammation following real-world use of Apellis’s geographic atrophy drug Syfovre crashed the company’s stock. On Saturday, the American Society of Retina Specialists' conference heard details on these and several more cases of retinal vasculitis, which can lead to blindness. Cowen analysts described the uptick in numbers as “disappointing” but added: “We believe it is a smaller number of cases than many investors had feared.” And the rate of these adverse events does not look as bad as with Beovu, the Novartis wet AMD drug for which sales expectations were sliced on toxicity fears. However, the cause of retinal vasculitis in the Syfovre-treated patients is still unknown, and it is also unclear how the side-effect worries might affect the drug’s launch, which has so far been strong. Apellis reported second-quarter product sales of $67.3m today, beating expectations of around $40m, but these were booked before the latest developments. Apellis’s share price fell 9% this morning, suggesting investors are yet to be convinced. Syfovre could soon be facing competition in geographic atrophy: Iveric’s avacincaptad pegol, now in the hands of Astellas, is due an FDA approval decision by August 19.

Two of this year’s biggest FDA approval decisions are due next month, that of Astellas’s Zimura and Biogen/Sage’s zuranolone. The latter is filed in major depressive disorder and postpartum depression and is expected to be approved. Zuranolone is forecast to be Biogen's biggest growth driver but questions remain on its commercial prospects given its short two-week course of therapy. Biogen needs to reinvigorate investor sentiment after announcing job cuts on its recent second quarter call, today it disclosed a hefty buyout of Reata. For Astellas, Zimura was gained through its $5.9bn acquisition of Iveric Bio, and is intended to treat geographic atrophy. On a cross-trial basis Zimura, a complement factor C5 inhibitor, looks fairly similar to Apellis’s approved Syfovre that targets C3. Syfovre got off to a strong launch in March but confidence in the therapy was knocked recently after six cases of retinal vasculitis were reported. The safety issue was not evident in clinical studies and could be related to manufacturing or delivery, noted TD Cowen analysts, leaving room for Zimura to pile on the pressure. More safety details are expected at this weekend's American society of retina specialists meeting.

Roche’s $4.3bn takeout of Spark Therapeutics has hardly set the world alight. Today there was more bad news for the deal, with Roche disclosing that it had discontinued the haemophilia A gene therapy candidate RG6358 (SPK-8016). A phase 1/2 study in patients with inhibitors had been due to complete this year; the first part of the trial, in subjects without inhibitors, yielded data in 2021. This is not the most advanced haemophilia A gene therapy candidate that Roche gained via Spark – that project, RG6357 (SPK-8011) is still in play and recently went into phase 3, the Swiss group said today. But Roche had originally hoped to start pivotal development in 2021, and earlier this year wrote off much of the value of SPK-8011 and other Spark-originated projects, effectively admitting that it had overpaid. More generally, excitement over haemophilia gene therapies is not what it was – Biomarin stock has slumped since FDA approval of Roctavian last month, amid ongoing doubts about how well the product will sell. The group has already lowered its Roctavian sales guidance for this year, from $200-100m to $50-150m, and some believe that number has further to fall.  

If Evrenzo cannot make a success of the anaemia market, what chance does Jesduvroq have? This seems to have been the question that led GSK management to call off its attempts to get the latter approved in new markets, a decision disclosed in its second-quarter results today. GSK had already pulled Jesduvroq’s filing in Europe after the CHMP recommended excluding non-dialysis patients from the project’s label, citing insufficient data to establish its safety in these patients. Withdrawing the filing was probably wise – even Fibrogen’s Evrenzo, with a label covering all patients regardless of dialysis requirements, is not doing well. A year ago, 2028 forecasts that would accrue to Astellas, which has rights in Europe and Japan, sat at $360m. Now they rest at just $99m, Evaluate Pharma consensus shows, possibly because an expensive product that only offers better convenience is struggling to make headway in a market dominated by the well known and now off patent EPO. The downside is that GSK’s “crown jewels” – the 10 projects the group highlighted two years ago as cumulatively worth $20bn – are looking shabbier as a result. Only Arexvy looks like it might live up to GSK's expectations, and even this has a great deal to prove commercially. 

Biogen chief exec Chris Viehbacher is cleaning house. The company announced during today's second-quarter results that it will cut 1,000 jobs in an attempt to save $700m in operating costs by 2025. This larger-than-expected move appears to be another attempt to ease investor disquiet since the poorly-received approval of the Alzheimer’s drug Aduhelm, which led to significant writedowns and the departure of several executives. While Biogen has had some wins recently, including approval of the Eisai-partnered Leqembi and the ALS product Qalsody, it is facing challenges to some of its most profitable franchises. The group has failed to block Sandoz developing a US biosimilar version of the MS drug Tysabri and on Friday the EMA gave its support for European approval. While Leqembi is expected to become profitable over time, difficulties with the required patient registry and reimbursement for PET scans mean it could be a very slow launch. On today’s conference call Viehbacher hinted at the direction the company might take, including deprioritising neurodegenerative diseases and increasing focus on rare diseases. Investors will be hoping these plans breathe some life to the group’s underperforming shares, though Biogen's stock fell 4% this morning.

Stoke Therapeutics' antisense oligonucleotide STK-001 reduces the frequency of convulsive seizures in Dravet syndrome patients – but not as much as previously. Updated data released today show that when results from two phase 1/2a paediatric studies of STK-001, Monarch and Admiral, are combined, seizure frequency was reduced by 18% between day 29 after the first dose and three months after the last dose. This was seen in 16 patients who had received three monthly 45mg doses. An earlier cut from the same trials, released in December, showed that this same dose had caused seizure reduction of 55% at the same time point, albeit in just six patients. In the 70mg cohort in Admiral, seizure frequency dropped by 42% – but this group was only eight patients strong. Further data ought to come in the first quarter of 2024. And Stoke has other challenges: the trials are on partial clinical hold in the US, and patients there may only receive a single 70mg dose of STK-001. The latest update detailed serious adverse reactions attributed to STK-001 in a patient receiving multiple 70mg doses. Stoke opened down 31%.