the end of the year and the beginning of the year are always a good time to look back on the past and look forward to the future. As 2021 comes to an end, we should also turn our attention to the upcoming 2022 to understand which major clinical trials are expected to announce the results next year. Recently, the well-known media in the industry, Fierce Biotech, took stock of the top ten clinical trials that are worth paying attention to next year. The list points out that these therapies under development all have significant potential. New molecular types such as CRISPR, RNAi, gene therapy, etc. are also constantly opening up new drug boundaries, which are expected to benefit patients around the world.
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In 2021, the approval of the Alzheimer's disease treatment Aduhelm (aucanumab) has undoubtedly brought a lot of traffic to this field and has also become the focus of hot discussion in the industry. Since it was approved in June, many pharmaceutical companies have also promoted their respective Alzheimer's disease treatments in order to obtain approval.
In these therapies, developed by Eli Lilly, the monoclonal antibody Donanemab targeting β amyloid has reached its primary endpoint in the Phase 2 clinical trial, delaying the clinical progress of early Alzheimer's disease patients 32%. In 2022, we are expected to see the head-to-head comparison results of donanemab and Aduhelm. At last week's investor meeting, Eli Lilly announced that it had launched a rolling application for donanemab, seeking accelerated approval from the US FDA. The company will also conduct a confirmatory Phase 3 clinical trial to evaluate its effectiveness in preventing Alzheimer's disease. In June this year, it was awarded the breakthrough therapy certification of FDA.
Roche's Genentech company's under-research anti-beta amyloid antibody therapy gantenerumab is currently being tested in a Phase 3 clinical trial and is expected to obtain clinical data in the second half of next year. Fierce Biotech noted that the main endpoint of the trial was cognitive ability, rather than just reducing amyloid beta. Once successful, it is of great significance. In October this year, the US FDA also awarded the breakthrough therapy certification of gantenerumab.
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Bijian and Eicai are developing another new Alzheimer's disease drug lecanemab, and have submitted a rolling marketing application to the FDA. According to the settings of clinical trials, the treatment is also expected to obtain phase 3 data in September 2022. It has also been awarded a breakthrough therapy certification in June this year.
CRISPR Therapeutics, a gene therapy developed by Vertex, is expected to transform patients with transfusion-dependent beta-thalassemia or severe sickle cell anemia.
CTX001 is an autologous CRISPR/Cas9 gene editing therapy under research. By modifying the patient's hematopoietic stem cells in vitro, high levels of fetal hemoglobin are produced in red blood cells . Feal hemoglobin is a form of hemoglobin that naturally exists at birth. Treatment with CTX001 can improve the fetal hemoglobin level in the patient, thereby alleviating the symptoms of these two types of diseases.
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In June this year, the two companies released preliminary clinical trial data from 22 patients, determining the potential of this therapy, making it hoped to become a potential one-time cure therapy for the treatment of these two diseases. At present, the phase 1/2 clinical trial of this trial has been recruited and is waiting for subsequent results. If all goes well, the two companies are expected to submit applications to the U.S. FDA in 2022. For CRISPR gene editing technology, this may become another major breakthrough.
Duchenne muscular dystrophy is a rare genetic disease caused by genetic mutations. For this reason, it has also become a potential target for gene therapy.In January this year, Pfizer announced that its under-proven gene therapy PF-06939926, which treats Duchenne muscular dystrophy, completed the first patient's dosage in the Phase 3 clinical trial. is also the first phase 3 clinical trial of gene therapy to treat this disease.
PF-06939926 is an intravenous gene therapy under development. It carries the "mini" mini-dystrophin transgene controlled by a human muscle-specific promoter in the adeno-associated virus 9 (AAV9) vector for targeted delivery to muscle tissue. Pfizer originally planned to obtain data from clinical trials before the end of 2022, but the adverse reactions in the trial complicate the problem. In Fierce Biotech's report, adverse reactions such as muscle weakness and cardiac inflammation have been mentioned. Yesterday, Pfizer announced that a patient died for unknown reasons in another early clinical trial of the therapy, which also added some uncertainty to his progress.
Sarepta Therapeutics's gene therapy collaboration with Roche SRP-9001 is a research gene therapy that delivers transgenes encoding microdystrophins to muscle tissues and promotes muscle production of microdystrophins. In October this year, the two companies launched global clinical trials, but it does not expect results next year. Instead, next year we are expected to see another data on the therapy in the mid-term to judge its potential.
Osteoarthritis affects the health of about 300 million people worldwide and is also one of the main causes of disability for the elderly, but there are not many corresponding therapies. LNA043 brought by Novartis is a modified ANGPTL3 protein. After intra-articular injection, this therapy is expected to repair cartilage damage and hit the cause of osteoarthritis, so it is expected to be the first osteoarthritis treatment to prevent joint degeneration.
Currently, this therapy is in a phase 2b clinical trial. At last year's investor meeting, Novartis also included it in the "high risk, high return" pipeline. In September this year, it obtained the fast track qualification of the US FDA. Novartis is expected to obtain the first batch of data before the end of next year. The complete data will have to wait until at least 2024. milvexian, jointly developed by J&J
JPY and Bristol-Myers Squibb , is a new generation of oral coagulation factor XIa inhibitor. In the Phase 2 clinical trial released this year, compared with commonly used anticoagulants, it not only significantly reduces venous thromboembolism after surgery, but also does not increase the risk of bleeding.
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This therapy is currently in another intermediate-term clinical trial to evaluate its effectiveness in preventing another stroke in patients with stroke or transient ischemic attacks. The trial is expected to obtain results in the first half of 2022. The combined results of the two trials of will determine whether the therapy can further enter the Phase 3 clinical trial.
The anticaftor (QWB251) brought by Novartis is a treatment for COPD disease. As one of the most important causes of death in the world, COPD is quite difficult to treat, and patients will experience symptoms such as shortness of breath and fatigue, which greatly affects their quality of life. At present, therapies for COPD include bronchodilator and corticosteroids, and new treatment plans are urgently needed.
Icenticaftor is an oral CFTR synergist, originally used for the treatment of cystic fibrosis . In patients with cystic fibrosis, CFTR proteins become inactive. . In COPD, due to oxidative stress such as smoking, the CFTR protein will also lose its effect. To this end, Novartis is also evaluating the role of this therapy in COPD.
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In the proof-of-concept study, the inenticaftor improved the patient's baseline lung function compared with placebo, but did not achieve the main endpoint of reducing lung infection with . Novartis has launched a phase 2b clinical trial and is expected to obtain results in the first half of next year.
In 2022, we are expected to witness the birth of the first respiratory syncytial virus vaccine. In young and older people, this virus is prone to severe infection and death. However, the vaccine development for this virus has always been difficult to say. But all this is expected to become history.
Respiratory syncytial virus vaccine brought by GlaxoSmithKline , Pfizer, and Johnson & Johnson are currently in full swing stage. The first two use recombinant protein subunit technology, and are targeted at the newborn and elderly population at the same time; the third uses adenovirus technology, mainly used in adults. This year, all three vaccines have achieved positive results in mid-term clinical trials and can stimulate neutralizing antibodies against respiratory syncytial virus . The results of their Phase 3 clinical trials are also expected to be announced in 2022.
oral selective estrogen receptor degradants are expected to become a new class of breast cancer treatment plans, and many companies are focusing on the research and development of new drugs in this field. At the San Antonio Breast Cancer Symposium earlier this month, Menarini and Radius announced the results of the Phase 3 clinical trial of the selective estrogen receptor degrader Ecrocestrant. In patients treated with CDK4/6 inhibitors, elacestrant monotherapy reduced the risk of disease progression or death by 30% compared with standard treatment (HR=0.697, 95% CI: 0.552, 0.880). At 12 months, the probability of patients in the elacestrant group without disease progression was 22.3%, and the value was 9.4% in the standard treatment group.
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In addition, Roche's giredestrant, Sanofi amcenstrant, and AstraZeneca camizestrant are also under development. Giredestrant is a potential "best-in-class" selective estrogen receptor degrader. It has a unique mechanism of action, which not only effectively degrades estrogen receptor , but also inhibits its function before degradation, thereby further improving the efficacy. Its phase 2 clinical interim data will be released this year, and more complete data will be released next year. According to Fierce Biotech's report, amcenestrant and camizestrant are expected to achieve results at the end of this year and early next year.
In September this year, MSD announced that it would spend about US$11.5 billion to acquire Acceleron Pharma. Through this acquisition, Merck will obtain the potential "first-in-class" therapy sotatercept. This potential therapy for pulmonary hypertension is currently in the third phase of clinical development. has the potential to become the cornerstone therapy for pulmonary hypertension.
Sotatercept is a potential "first-in-class" IIA type activator receptor (ActRIIA) fusion protein. It fuses ActRIIA's engineered extracellular domain with the Fc end of the antibody, which blocks activin from binding to receptor on cell membrane, thereby reducing activin-mediated signaling. It has been awarded the breakthrough therapy certification granted by the FDA, and This is also the first pulmonary hypertension under investigation to obtain breakthrough therapy certification.
In 2022, its clinical trials will usher in key results. Industry analysts believe that if successful, it will hopefully become a blockbuster drug. In the Phase 2 clinical trial, it has shown great potential.
Since the first RNAi therapy was approved, this field has made great progress and development in recent years. Alnylam, a star company in the field of RNAi, has cooperated with Novartis to bring Leqvio (inclisiran) to lower cholesterol in Europe. This therapy only requires twice a year to be effective. one-time treatment has also become a major development direction for RNAi therapy in the future.
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And zilebesiran is an RNAi therapy with a similar design. It also treats a common disease - Hypertension . Hypertension is an important risk factor for cardiovascular disease, and many patients with hypertension need to take daily medication to alleviate the condition. Zilebesiran is an RNAi therapy targeting mRNA that expresses angiotensin . By reducing the production of angiotensin in the liver, this therapy can lower the levels of angiotensin, thereby achieving consistent and long-lasting blood pressure reduction.
Its phase 2 clinical trial was launched in November this year and is expected to obtain results by the end of next year. By design, this therapy can be given 2 to 4 times a year.
It is not difficult for us to see some trends from these clinical trials worth paying attention to. First of all, new molecular types like CRISPR, RNAi, gene therapy, etc. are playing an increasingly important role , and are expected to become the backbone of innovative therapies in the future. Secondly, many diseases that were originally without medicine or urgently needed innovative therapies are also receiving more and more attention , and are expected to achieve a zero breakthrough. Finally, we also see that , whether it is a common disease that affects hundreds of millions of people, or a rare disease, may usher in good progress next year, , reflecting the pharmaceutical industry's commitment to benefit human health.
We look forward to these therapies achieving positive results in the future and bringing more hope to more patients as soon as possible!
Reference:
[1] Fierce Biotech’s top 10 data readouts in 2022, Retrieved December, from https://www.fiercebiotech.com/special-report/fierce-biotech-s-top-10-data-readouts-2022
[2] One of Pfizer’s Duchenne gene therapy trials put on hold in wake of patient death as high-dose AAV concerns still cloud field, Retrieved December 21, 2021, from https://endpts.com/one-of-pfizers-duchenne-gene-therapy-trials-put-on-hold-in-wake-of-patient-death-as-high-dose-aav-concerns-still-cloud-field/
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