Vantage Snippets are short summaries of breaking news stories.

Eliquis: the cardio drug that cannot be beat

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.

Top 10 cardiovascular drug sales: 2023
Product Company Indications 2023e sales ($bn)
Eliquis Bristol Myers Squibb/Pfizer Stroke prophylaxis 12.2
Entresto Novartis Chronic heart failure 5.8
Xarelto Bayer/J&J Stroke prophylaxis; Myocardial infarction, acute 2.9
Opsumit Johnson & Johnson Pulmonary hypertension 1.9
Lipitor Viatris Hyperlipidaemia 1.6
Repatha Amgen Hyperlipidaemia 1.6
Uptravi Johnson & Johnson Pulmonary hypertension 1.5
Tyvaso United Therapeutics Pulmonary hypertension 1.4
Lixiana Daiichi Sankyo Stroke prophylaxis 1.4
Activase Roche Myocardial infarction, acute 1.3
Source: Evaluate Pharma.


Top 10 cardiovascular companies 2023 & 2028
Company 2023e cardiovascular sales ($bn)   Company 2028e cardiovascular sales ($bn)
Novartis 7.8    Novartis 6.9
Pfizer 6.8   Bristol Myers Squibb 5.4
Bristol Myers Squibb 5.8   Merck & Co 4.0
Bayer 5.2   United Therapeutics 3.9
Johnson & Johnson 5.1   Pfizer 3.8
AstraZeneca 4.0   Sanofi 3.5
Sanofi 3.7   Bayer 3.4
Viatris 2.9   Johnson & Johnson 3.2
United Therapeutics 2.3   AstraZeneca 3.1
Daiichi Sankyo 2.0   Viatris 2.8
Source: Evaluate Pharma.


Top 10 cardiovascular drug sales: 2028
Product Company Indications 2028e sales ($bn)
Eliquis Bristol Myers Squibb/Pfizer Stroke prophylaxis 6.7
Tyvaso United Therapeutics Pulmonary hypertension 2.8
Entresto Novartis Chronic heart failure 2.7
Sotatercept Merck & Co Pulmonary hypertension 2.6
Repatha Amgen Hyperlipidaemia 2.2
Camzyos Bristol Myers Squibb Hypertrophic cardiomyopathy; Chronic heart failure 2.1
Leqvio Novartis Hyperlipidaemia; Atherosclerosis 2
Aficamten Cytokinetics Hypertrophic cardiomyopathy 1.7
Lipitor Viatris Hyperlipidaemia 1.5
Activase Roche Myocardial infarction, acute 1.5
Source: Evaluate Pharma.


Keytruda and Gardasil lead Merck's earnings beat

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.

Voxzogo saves the day for Biomarin

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. 

US FDA approval and panel tracker: July 2023

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.

Notable first-time US approval decisions in July 2023
Project Company Indication(s) 2028e SBI ($m) Outcome
Beyfortus (nirsevimab) Astrazeneca/Sanofi/Sobi Prevention of RSV lower respiratory tract disease in neonates and infants born during or entering their first RSV season, and in children up to 2 years old who remain vulnerable to severe disease through their second season 1,727 Approved
Qdenga (TAK-003) Takeda Dengue vaccine (4-60 years) 922 BLA withdrawn (data collection issues)
Xdemvy (TP-03) Tarsus Demodex blepharitis 497 Approved
Verrica Molluscum contagiosum in patients 2 years and older 212 Approved
Cyfendus (AV7909) Emergent Biosolutions Two-dose anthrax vaccine for post-exposure prophylaxis use 212 Approved
Lymphir (denileukin diftitox, I/Ontak, E7777)  Citius Pharmaceuticals  Cutaneous persistent or recurrent T-cell lymphoma 195 CRL
Quizartinib (Vanflyta) + standard cytarabine and anthracycline induction Daiichi Sankyo Newly diagnosed FLT3-ITD­ +ve AML  116 Approved
Risvan (Doria/
risperidone ISM)
Laboratorios Farmacéuticos ROVI Schizophrenia - CRL
Balfaxar (Octaplex) Octapharma Warfarin reversal in urgent surgery and invasive procedures - Approved
Sources: Evaluate Pharma & company releases.


Supplementary and other notable approval decisions in July 2023
Product Company Indication (clinical trial) Outcome
Leqembi Eisai/Biogen Alzheimer's disease - full approval Approved
Leqvio Novartis Adults with high LDL-C and who are at increased risk of heart disease Approved
Veklury Gilead Covid-19 patients with severe renal impairment, including those on dialysis (Redpine) Approved
Ervebo Merck Prevention of Ebola virus disease caused by Zaire ebolavirus in individuals 1-17 years of age Approved
Jemperli + chemo Anaptysbio/GSK Adult patients with mismatch repair deficient/microsatellite instability-high primary advanced or recurrent endometrial cancer (part 1 of Ruby) Approved (~ 2 months early)
Sources: Evaluate Pharma & company releases.

ASRS 2023 – Syfovre’s side-effect questions still loom large

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.

Reported cases of retinal vasculitis with Apellis's Syfovre
  Number of cases
  Occlusive Non-occlusive
ASRS ReST Committee notification 15 Jul 2023 6 -
Apellis update 29 Jul 2023 4* 3*
ASRS ReST Committee update 29 Jul 2023 8** 3^
*Confirmed cases only; **includes 1 unconfirmed case; ^includes 2 unconfirmed cases; ReST=Research and Safety in Therapeutics Committee. Source: ASRS & company statements.

Go or no go? Biogen and Astellas head towards key Pdufas

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.

Notable first-time US approval decisions due in August 2023
Project Company Pdufa date Indication(s) 2028e SBI ($m) Note
Ryoncil (remestemcel-L) Mesoblast/ JCR Pharmaceuticals 2 Aug (resubmission) Children with steroid-refractory acute graft versus host disease 223 Mesoblast can’t catch a break
PDP-716 (0.35% brimonidine tartrate) Visiox 4 Aug Glaucoma - -
Zuranolone Biogen/Sage 5 Aug Major depressive disorder and postpartum depression 1,177 See text
Talvey (talquetamab) J&J Estimated 9 Aug Relapsed or refractory multiple myeloma 300 Bispecific T-cell engager antibody targeting both GPRC5D and CD3
Avasopasem Galera 9 Aug Radiotherapy-induced severe oral mucositis - Selective dismutase mimetic
Hepzato kit Delcath 14 Aug (resubmission) Unresectable hepatic-dominant metastatic ocular melanoma - Previous CRL in 2013, after a negative adcom, needed another trial
Sohonos (palovarotene capsules) Ipsen 16 Aug (resubmission) Fibrodysplasia ossificans progressiva - After an earlier CRL received a positive adcom
Zimura Astellas (Iveric Bio) 19 Aug Geographic atrophy 1,179 See text
Pozelimab Regeneron 20 Aug Adults and children as young as 1 year of age with Chaple disease - Subcutaneous anti-complement C5 antibody
Elranatamab Pfizer Estimated 22 Aug Relapsed or refractory multiple myeloma  829 BCMA T-cell engager
Lytenava (ONS-5010) Outlook 29 Aug Wet AMD 590 Opthalmic Avastin
VLA1553 Valneva End of Aug Single-shot chikungunya vaccine 333 Bavarian falls short of Valneva in Chikungunya
Tuoyi (toripalimab) Coherus Q3 Nasopharyngeal carcinoma - Previous inspection delays
Pombiliti + Opfolda Amicus Q3 Adults with late-onset Pompe disease 443 Previous inspection delays
Bimzelx UCB Q3 (resubmission) Plaque psoriasis 937 Delayed from Q2 to Q3, previous CRL due to failed pre-approval inspections
Etrasimod Pfizer H2 Ulcerative colitis 825 S1P inhibitor, competitor to Bristol's Zeposia (Pfizer seeks to put etrasimod first)
SBI: sales by indication. Sources: Evaluate Pharma & company releases.


Supplementary and other notable approval decisions due in August 2023
Product Company Indication (clinical trial) Date
Abrysvo Pfizer Prevention of (severe) lower respiratory tract disease caused by RSV in infants from birth through 6 months by active immunisation of pregnant individuals Aug
Lonsurf Taiho/Otsuka Monotherapy or in combination with bevacizumab for the treatment of adult patients with metastatic colorectal cancer (Sunlight) 13 Aug
Daxxify Revance Cervical dystonia (Aspen-1, Aspen OLS) 19 Aug
Ingrezza Neurocrine Chorea associated with Huntington disease (Kinect-HD, Kinect-HD2) 20 Aug
Reblozyl Bristol First-line treatment of anaemia in lower risk myelodysplastic syndromes 28 Aug
Jardiance Lilly/Boehringer Reduce the risk of kidney disease progression and cardiovascular death in adults with chronic kidney disease (Empa-Kidney) Estimated Q3
AVT04 (Stelara biosimilar) Alvotech/Teva Inflammatory conditions H2
Cosentyx Novartis Hidradenitis suppurativa (Sunshine, Sunrise) H2
Intravenous Cosentyx Novartis Adult patients with psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis (Invigorate 1, Invigorate 2) H2
Sources: Evaluate Pharma & company releases.

Roche loses more of its Spark

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.  

Haemophilia A gene therapies
Project Company Status
Roctavian (valoctocogene roxaparvovec) Biomarin Approved in US June 2023, EU Aug 2022
Giroctocogene fitelparvovec (SB-525) Pfizer/Sangamo Data from ph3 Affine due by H1 2024  
RG6357/SPK-8011 Roche Ph3 initiated H1 2023 (no entry)
ASC618 ASC Therapeutics Ph1/2 completes Dec 2023
RG6358/SPK-8016 Roche Discontinued Jul 2023
Source: Evaluate Pharma &

GSK admits anaemia defeat

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. 

Diamonds and the rough: GSK's "crown jewels"
Product/project Description GSK's non-risk adjusted peak sales* Status 2028e sales ($m)**
Arexvy (RSVPreF3) Adult RSV vaccine >£3bn Approved in US May 2023 2,219
Apretude (cabotegravir) Long-acting HIV therapy & PrEP >£2bn Approved for therapy Jan 2021 & Prep Dec 2021 847
Zejula Parp inhibitor (from Tesaro) >£2bn 2L ovarian cancer maintenance use restricted to Brca+ve pts Nov 2022; 1L maintenance use not affected 849
Bepirovirsen (GSK3228836) Hepatitis B antisense oligonucleotide (licensed from Ionis) >£2bn Two ph3 trials could report 2025-6 208
Depemokimab (GSK3511294) Long-acting anti-IL5 for asthma £1-2bn In ph3 trials for hypereosinophilic syndrome, asthma, eosinophilic granulomatosis and nasal polyps 219
Jemperli PD-1 inhibitor (from Tesaro) £1-2bn Part 1 of ph3 Ruby trial in 1L endometrial cancer toplined positive, progressing to part 2 readout 318
Men ABCWY Pentavalent meningitis vaccine £1-2bn Ph3 trial toplined hit in Mar 2023 756
Gepotidacin uUTIs £0.5-1bn Eagle-2 & 3 stopped early for efficacy Nov 2022 350
Jesduvroq/Duvroq (daprodustat) HIF-PH inhibitor for anaemia in CKD £0.5-1bn Approved in US and Japan for non-dialysis patients; filing pulled in EU and no new filings planned 304
Otilimab Anti-GM-CSF MAb for rheumatoid arthritis £1-2bn Discontinued Oct 2022 following lacklustre results from Contrast-1, 2 & 3 -
Blenrep BCMA-targeting ADC >£3bn Withdrawn from US market Nov 2022 after failure of confirmatory Dreamm-3 trial -
GSK3888550A Maternal RSV vaccine £1-2bn Discontinued Feb 2022 -
*Based on GSK's June 2021 investor event; **2028 forecasts only given for assets still in play; GSK sales only. Source: GSK presentation & Evaluate Pharma. 

Viehbacher swings the axe at Biogen

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.

Dravet efficacy wanes for Stoke

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%.

An updated cut from Monarch and Admiral
Dose 3 x 30mg (N=18) 3 x 45mg (N=16) 3 x 70mg (N=5) + 2 x 70mg (N=6)
Median reduction from baseline in convulsive seizure frequency      
    day 29 through 3 months after last dose 28% 18% 42%
        no of pts analysed 17 16 8
    day 29 through 6 months after last dose 24% 26% 42%
        no of pts analysed 16 14 6
Source: company release.