Biotech’s key upcoming clinical results

Moderna, Biomarin and Daiichi Sankyo will begin 2023 with important data reveals.

After delving into the key upcoming catalysts for big pharma, Evaluate Vantage has found the big data reveals expected for biotech companies with a market cap of at least $1bn.   

Moderna will report vaccine data in cytomegalovirus (CMV) and respiratory syncytial virus (RSV); although the group lags competitors in the latter, it looks to have the lead in the former. Elsewhere, Biomarin will report three-year data with its haemophilia A gene therapy Roctavian, a key metric for the FDA, and Daiichi is taking a solo approach with its latest antibody-drug conjugate patritumab deruxtecan, with data in lung cancer. 

Moderna's next act 

Moving on from its work tackling coronavirus, Moderna is turning its vaccine technology to RSV and CMV. 

The latter is a common virus that is usually harmless. However, it can cause serious health problems in some babies who get the virus before birth, and in people who have a weakened immune system. Antivirals like Merck & Co's Prevymis are given prophylactically in some transplant patients, but these are far from ideal, and with no approved vaccines Moderna looks to have the most advanced candidate.    

mRNA-1647 contains six mRNAs, which encode for two proteins located on the surface of CMV. Its study, CMVictory, is enrolling women of childbearing age (16-40 years old) who are seronegative and at high risk of contracting CMV, via direct exposure to at least one child under 5 years old. 

In total, participants will receive three 100µg doses against placebo. The primary measures are safety and seroconversion, from negative to positive 28 days and up to 24 months after the third injection. Secondary measures include titres of neutralising and binding antibodies. 

Of the big players both Merck & Co and Sanofi completed early studies with vaccine projects, but further development seems to have stalled, while GSK’S GSK3993129A is in phase 1/2. 

In RSV, Moderna is lagging competitors: both GSK and Pfizer have filed their adult vaccine candidates and an FDA decision for both is expected in May. 

Moderna’s ConquerRSV study is in adults aged 60 and older, with 37,000 participants. Efficacy of a single mRNA-1345 dose will be measured as the prevention of a first episode of RSV-associated lower respiratory tract disease compared with placebo, from 14 days post injection through 12 months. 

On this measure GSK’s GSK3844766A, or RSVPreF3 OA, looks like the one to beat, with an impressive 82.6% efficacy, assessed over 7-10 months, while Pfizer’s project hit the 66.7% mark. The competition does not stop with GSK or Pfizer, however: Johnson & Johnson’s VAC18193 is also in phase 3. 

FDA’s request 

After a previous knockback the end is in sight, again, for Biomarin’s haemophilia A gene therapy Roctavian. The project is already filed in the US with a Pdufa date in March, but first Roctavian needs to pass muster with long-term data, due early next year. 

Three-year results from the Gener8-1 study were requested by the FDA; if the regulator considers these a major amendment, this will delay the Pdufa by three months. 

The focus will be on the trend in factor VIII levels and annualised bleeding rates (ABR) from year two to three. Biomarin has already released some three-year data in a small subset of patients, with levels of FVIII activity dropping from the second year.  

However, the bleeding rate still looked to be under control, with a mean 0.6 per year, from 0.7 at two years. William Blair analysts believe that the full three-year data need to show a mean ABR of less than 1 and median of 0. 

The closest gene therapy competitor is Sangamo/Pfizer’s giroctocogene fitelparvovec, with pivotal data due in the first half of 2024

Going solo 

Daiichi, alongside Astrazeneca, has made huge strides with its antibody-drug conjugates, and data are now due from one that Daiichi has, so far, kept to itself.  

Patritumab deruxtecan targets Her3, and results from the registrational Herthena-Lung01 study could come in the first half of next year. The setting is metastatic or locally advanced EGFR-mutated NSCLC. 

The open-label study has two arms, a 5.6mg/kg fixed dose regimen or an up-titration to 6.4mg/kg. The primary endpoint is objective response rate. Data from an earlier study showed impressive response rates, but there were issues with interstitial lung disease, a common toxicity with Daiichi and Astra’s ADC Enhertu. 

The table below contains a fuller list of upcoming catalysts with consensus forecasts from Evaluate Pharma. 

Big biotech's Q1 clinical catalysts
Project Company  Therapy area Q1 clinical catalyst 2028e indication sales ($m) Note/ Vantage coverage
NTLA-2001 Intellia Therapeutics/ Regeneron ATTR amyloidosis Further updates from ph1 in 2023 1,980 Intellia delivers a second knockdown success
KarXT Karuna Schizoprenia Ph3 Emergent-3 1,638 Emergent-2 was positive, filing planned for mid-2023 (Karuna bucks the neuro trend)
Valoctocogene roxaparvovec (valrox, Roctavian) Biomarin Haemophilia A Ph3 GENEr8-1 3yr data 1,420 See text
mRNA-1647 Moderna CMV (vaccine) Ph3 CMVictory, PC January 1,232 See text
Subcutaneous efgartigimod Argenx Chronic inflammatory demyelinating polyneuropathy Ph2 registrational Adhere 1,168* Anti-FcRn, approved as IV version (Vyvgart) in generalised myasthenia gravis; SC has a Pdufa in March in gMG
Elahere (mirvetuximab) Immunogen Folate receptor alpha-high platinum-resistant ovarian cancer previously treated with 1-3 systemics Confirmatory Mirasol study, vs chemo early 2023 759 Given accelerated approval in Nov, key for Sutro (Immunogen puts Sutro on alert)
ARO-ANG3 Arrowhead Mixed dyslipidaemia Ph2 Arches-2 701 Anti-angiopoietin-like 3 RNAi therapeutic; Regeneron's Evkeeza, a MAb, is approved in HoHF
Day One Biopharmaceuticals Paediatric and young adults with relapsed or progressive low-grade glioma  Ph2 Firefly-1 topline for full pivotal study population 611 Positive interim data reported already, filing due H1, pivotal study to start soon (Firefly glows for Day One)
Acadia Negative symptoms of schizophrenia Ph3 Advance-2 2023 520 Received two CRLs in dementia-related psychosis & Alz-related dementia, narrow win in earlier schizophrenia Advance study
FT596 +/-
Fate R/r B-cell lymphoma Ph1 (possibly at R&D event due Q1) 375 Anti-CD19 Car-NK
Patritumab deruxtecan Daiichi Sankyo 3L EGFR mutated NSCLC Ph2 registrational Herthena-Lung01 H1 329 See text
Sparsentan Travere Focal segmental glomerulosclerosis Pivotal Ph3 Duplex, 2 year eGFR data, H1 302 FDA initially knocked back Travere's plan for accelerated approval filing based on interim proteinuria data
Magrolimab Gilead 1L high-risk MDS Ph3 Enhance interim 298 Anti-CD47 MAb
Pivlaz (clazosentan) Idorsia Preventing  complications related to cerebral vasospasm in adults with aneurysmal subarachnoid haemorrhage Ph3 React 228 On the market in Japan, this is a global study
mRNA-1345 Moderna RSV (adults ≥60; vaccine) Pivotal Ph2/3 ConquerRSV 1st interim analysis 192 See text
RG6180 +/- Keytruda
1L metastatic melanoma Ph2 Imcode001 guided to 2023 172 Also known as autogene cevumeran, primary is PFS, part of iNeST personalised cancer vaccine platform
Vax-24 Vaxcyte Pneumococcal vaccine (adults aged 65 and over) Ph2 vs Prevnar 20, topline safety, tolerability and immunogenicity H1 - 24-valent vaccine; note GSK bought Affinivax for its early-stage 24-valent vaccine
Sugemalimab (Cejemly) EQRX Stage III NSCLC Ph3 Gemstone-301, interim OS - China study, seen stat sig PFS data already (anti-PD1; US development in stage IV NSCLC discontinued)
Fibrogen Anaemia in low-risk myelodysplastic syndrome (MDS)  Ph3 Matterhorn - Last chance to salvage something for roxa, in the US at least (Pressure piles up on pamrevlumab)
*Forecasts under Vyvgart. PC: primary completion, SC: subcutaneous, IV: intravenous. Source: Evaluate Pharma &

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