The most noteworthy blockbuster new drug trial results in 2022!

In the fields of cancer, central nervous system diseases, cardiovascular diseases, arthritis, and rare diseases, there are a number of drugs with blockbuster potential therapies entering the advanced stage of clinical trials, and research data will be released in 2022

These important trial results will determine the next development plan, regulatory approval and even the future market fate of these drugs, which has attracted much attention from the industry

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Innovation in traditional fields

Arthritis: Novartis LNA043 (ANGPTL3 agonist)

Developed by the Novartis Institutes for Biomedical Research (NIBR), LNA043 is an improved recombinant version of human ANGPTL3 that prompts cells in the joint to regenerate cartilage and is administered by direct injection into diseased joints

The first results from the Phase IIb trial are expected by the end of 2022, but follow-up studies will not be completed until 2024

Anticoagulants: BMS/Johnson & Johnson milvexian (factor XIa inhibitor)

  Milvexian rivals the efficacy of drugs targeting factor Xa, such as Eliquis and J&J/Bayer's Xarelto (rivaroxaban), while avoiding the increased risk of bleeding side effects

  Results from the AXIOMATIC-TKR trial showed that milvexian prevented venous thromboembolism (VTE) in patients undergoing total knee replacement surgery without increasing the risk of bleeding

  All eyes are now on the second interim trial, AXIOMATIC-SSP, to investigate the potential of milvexian to prevent secondary stroke in patients with stroke or transient ischemic attack

Hypertension: Alnylam's zilebesiran (RNAi Drug)

  Alnylam's RNAi drug zilebesiran (ALN-AGT) targets angiotensinogen (AGT), which in turn regulates blood pressure in the body, and requires only two or four doses per year

  Alnylam has started a phase II trial in mild to moderate hypertension (KARDIA-1), which is testing monotherapy in about 375 patients to see if it can safely control blood pressure, with results due Announced by the end of 2022

  Alnylam also plans to initiate a second, slightly larger, phase 2 trial (KARDIA-2), which will examine the drug's potential as an add-on therapy to traditional antihypertensive drugs in approximately 800 patients with uncontrolled hypertension
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SERD welcomes breakthrough

The four competing, or the latecomer will come out on top

  In 2022, oral selective estrogen receptor degraders (SERDs) will become a widely used alternative to injectable drugs in breast cancer
.
  

  The development of SERD has always been a race between AstraZeneca, Roche and Sanofi, with Menarini/Radius joining in and quickly taking the lead
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  Menarini and Radius reported top-line data from a Phase III trial of the collaborative development of elacestrant in October 2021, with marketing applications to be submitted in the U.
S.
and Europe in 2022
.
The two companies plan to release complete data in the near future, and are expected to surpass Roche giredestrant, Sanofi amcenestrant and AstraZeneca camizestrant to be approved first
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  Meanwhile, Sanofi has been leading the charge ahead of a delay in its AMEERA-3 study, amcenestrant as a second-line therapy that could report results in early 2022
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In the SERENA-2 trial, AstraZeneca's camizestrant had a similar trial design and study schedule
.
Roche's giredestrant's acelERA study is a second- and third-line therapy, and results are expected in the first half of 2022
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Gene therapy heats up

SCD/beta thalassemia: two rivalries

  CRISPR/Vertex is competing with Bluebird to bring one-off gene therapies for the rare blood diseases sickle cell disease (SCD) and beta thalassemia to the U.
S.
market
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  CRISPR/Vertex has been steadily updating data from a Phase I/II trial of its gene-editing therapy CTX001
.
The study patients are now fully enrolled and are awaiting the end of the follow-up period before finalizing the results
.
If all goes well, CRISPR/Vertex plans to submit a marketing application to the FDA by the end of 2022
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  CTX001 is an ex vivo gene therapy that uses CRISPR/Cas9 gene editing to modify a patient's hematopoietic stem cells to produce red blood cells with high levels of fetal hemoglobin to replace the defective version seen in thalassemia and SCD
.
  

  Previous data from the thalassemia trial CLIMB-111 and the SCD trial CLIMB-211 showed an increase in fetal hemoglobin levels, a reduction in SCD pain episodes, and a reduction in thalassemia dependence on blood transfusions
.
  

  However, these trials also face some questions, including whether their effects are long-lasting enough? Is it enough for CTX001 to be considered a functional cure for these diseases? There are indications that fetal hemoglobin levels decline over time
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Safety is another consideration, with some adverse events occurring with CTX001 treatment
.
  

  Bluebird's thalassemia therapy Zynteglo (betibeglogene autotemcel or beti-cel) was approved in Europe in 2019, but pulled out of Europe entirely without a pricing agreement in Germany in summer 2021
.
In September 2021, Bluebird submitted a marketing application for beti-cel to the FDA for thalassemia
.
  

  Bluebird's troubles in Europe may present an opportunity for Vertex/CRISPR
.
    

DMD: Top 3 Patterns

  Duchenne muscular dystrophy (DMD) gene therapy development is shaping up to be a three-way competition: Pfizer, Sarepta and Solid Bio are all working on gene therapy to boost dystrophin production, likely to enter in 2022 Final sprint stage
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  Pfizer was the first to advance its fordistrogene movaparvovec (PF-06939926) drug candidate into a Phase III clinical trial, but was forced to tighten after three cases of muscle weakness, including inflammation of heart tissue or myocarditis, were reported its entry criteria
.
Currently, all enrolled patients are in Europe and Asia, as the FDA has not yet approved Pfizer to begin treating patients in the United States
.
While Pfizer still expects the trial to report results by the end of 2022, it will actually have to push back the timeline
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  Meanwhile, Sarepta is conducting a Phase III EMBARK trial of its drug candidate SRP-9001, which begins in October 2021
.
That's not a key figure for Sarepta in 2022, though
.
The company is awaiting a second data set from its interim study, which missed the primary endpoint when it reports Phase 1 data in early 2021
.
SRP-9001 did show a trend to improve walking ability in DMD patients, but it was not statistically significant, so the 2022 data will be a key indicator of SRP-9001's potential
.
If positive, Sarepta may submit a marketing application to the FDA ahead of schedule
.
  

  Another gene therapy contender is Solid Bio's SGT-001, which is slightly behind both competitors in development
.
Solid's interim results from a Phase I/II study in 2021 were disappointing
.
The study was delayed by the FDA in 2019 due to liver and platelet side effects
.
However, Solid will be trialing more patients
.
By the end of 2022, the potential of the three gene therapies will become clearer
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RSV, the new battlefield for vaccines

The top three advance to the final

  GlaxoSmithKline (GSK), Pfizer and Johnson & Johnson, who will be the first to bring a respiratory syncytial virus (RSV) vaccine to market? 2022 should be a big year for measuring results
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  GSK's GSK3844766A/GSK3888550A and Pfizer's RSVpreF are recombinant protein subunit vaccines, while Johnson & Johnson's adenovirus vaccine VAC18193 uses the same technology platform as its COVID-19 vaccine
.
GSK and Pfizer's vaccine is being developed for two applications: as a maternal vaccine designed to protect infants from RSV infection in the first few months of life, and as an injection for the elderly
.
Johnson & Johnson is currently focusing on the adult market
.
  

  In 2021, all three vaccines achieved positive results in mid-stage trials focused primarily on stimulating RSV-neutralizing antibodies, and all entered Phase III studies, with data expected in 2022
.
  

  Pfizer is well ahead and expects to report results from a Phase III trial of RSVpreF in adults (RENOIR study) and maternal patients (MATISSE study) in the first half of 2022
.
  

  Meanwhile, GSK expects interim results from its AReSVi004 study of GSK3844766A, available in adults with its proprietary AS01 adjuvant, to be published in 2022, with a final readout in 2024; Phase III from its unadjuvanted parental injection of GSK3888550A The first data from the trial will also be released
.
For J&J, key data will come from the EVERGREEN study of VAC18193 in the second half of 2022
.
 

mRNA vaccines are at an earlier stage

  Other drugmakers have RSV vaccine candidates in earlier stages of development, including an mRNA-based vaccine from Moderna, which started Phase II/III trials in adults in November 2021
.
Sanofi has said it expects Phase I/II results of a live attenuated RSV vaccine for young children in 2022
.
The company also has an mRNA vaccine for the adult market, which is scheduled to begin clinical testing in 2023
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Rare disease drug chasing higher goals

Can cystic fibrosis drug conversion for COPD be successful?

  Novartis' icenticaftor (QWB251), an orally active potentiator or opener of the cystic fibrosis transmembrane conductance regulator (CFTR), is being used by Novartis as a chronic Obstructive pulmonary disease (COPD) drug development
.
So far, research results have been mixed
.
  

  In a proof-of-concept study, icenticaftor achieved modest improvements compared to placebo in changes in baseline lung function measured before and after bronchodilator use in patients
.
The drug also improved biomarkers of inflammation and reduced bacterial colonization of sputum
.
  

  But the drug failed to achieve the study's main goal, which was to reduce lung infections, a common complication of COPD
.
However, Novartis is confident enough to start a Phase IIb dose-ranging study
.
Recruitment has now been completed, results will be announced in the first half of 2022, and a Phase III study is planned for 2023
.
  

  icentifator is also conducting another parallel proof-of-concept study for bronchiectasis
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Sotatercept is expected to become the new standard of PAH treatment?

  Merck's $11.
5 billion acquisition of Acceleron, one of the largest biotech M&A deals of 2021, focuses on pulmonary arterial hypertension (PAH) drug candidate Sotatercept
.
  

  Sotatercept is critical to the deal, and Acceleron's activist investors have tried to hold off on the acquisition pending the results of an ongoing Phase III trial, in hopes of raising the offer
.
  

  A major turning point for the deal will come in 2022, when the STELLAR trial of Sotatercept is announced, and the drug's prospects in the crowded PAH market will become clearer
.
  

  The currently marketed PAH drugs mainly treat the symptoms of PAH by relaxing blood vessels, including endothelin receptor antagonists (Actelion's Tracleer and Opsumit/Gilead's Letairis), repurposed PDE5 inhibitors (Viatris' Revatio and United's Adcirca) ) and prostacyclin (Remodulin by United and Uptravi by Janssen)
.
  

  Sotatercept is a TGF-β modulator designed to rebalance BMP and activin signaling pathways thought to contribute to vascular remodeling in PAH
.
By contrast, sotatercept aims to be the first therapy to address the underlying pathology of the disease
.
If sotatercept reaches the endpoint in STELLAR, it is expected to become the new standard of PAH treatment
.