The much-awaited Drugs to Watch list by global analytics company Clarivate is out. Let’s do a deep dive into some of the drugs that made it to the list, and obtained regulatory approval in 2023. These drugs may be on their way to transform therapeutic approaches in the next few years.
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Johnson & Johnson’s niraparib and abiraterone acetate, more commonly known as AKEEGA, was one of the new drugs to make it to the list. Making it the first and only U.S. Food and Drug Administration (FDA)-approved dual action tablet combining a PARP inhibitor and a hormonal therapy to provide precision medicine for patients with BRCA-positive metastatic castration-resistant prostate cancer (mCRPC), this marks a major milestone in prostate cancer research.
Studies have shown that people with the BRCA gene have higher odds of developing prostate cancer. And with 299,010 new cases estimated to be diagnosed this year in the U.S. alone where 35,250 deaths are predicted, according to the American Cancer Society, there is a need for more treatment options for people.
That’s why AKEEGA’s approval back in August is seen as a significant one. Being a PARP inhibitor, Niraparib blocks the enzymes PARP-1 and PARP-2, both of which help in DNA repair in cells. Preventing DNA repair promotes the death of cancer cells. Abiraterone acetate hinders the enzyme CYP17, which is responsible for testosterone production in the body. Since prostate cancer is driven by testosterone which aids in the growth of cancer cells, this active substance slows the progression of the disease.
The approval came after the drug showed encouraging results in a phase 3 trial. The drug combination showed a 47% risk reduction for Radiographic Progression-Free Survival (rPFS) in patients with the BRCA mutation.
However, the drug comes with warnings of potential side effects that include myelosuppression – resulting in a smaller number of blood cells produced – and liver damage.
Hemophilia A is a hereditary bleeding disorder that occurs when the body does not have clotting factor VIII, due to mutations on the F8 gene present on the X chromosome. People with this protein deficiency may experience excessive blood loss and even spontaneous bleeding episodes.
To treat this debilitating disorder, Sanofi and rare disease company Sobi collaborated to bring efanesoctocog alfa to the market. Known by its brand name ALTUVIIIO, it is a new class of factor VIII replacement therapy against hemophilia A. This prophylactic treatment works by temporarily replacing the lacking coagulation factor VIII, to decrease the number of bleeding episodes. Approved by the FDA almost a year ago, the drug performed well in the clinic. A phase 3 study found that the once-weekly infusion provided significant bleed protection for people with severe hemophilia A, with a mean annualized bleeding rate (ABR) – a treatment measure for hemophilia – of 0.70. It also prevented joint bleeds.
This new drug was also found to be superior to other hemophilia A prophylactic therapies as it is the first of its kind to deliver normal to near-normal factor activity levels with a weekly dosing.
Respiratory syncytial virus (RSV) affects around 64 million people worldwide, every year, according to the National Institute of Allergy and Infectious Diseases. A recent study found that a vaccine could cut the number of young children hospitalized with RSV by 80%. And now, that is possible with Pfizer’s ABRYSVO.
ABRYSVO is a vaccine that works by inducing an immune response against the virus. It contains two prefusion F (preF) proteins that protect against RSV A and B strains of the pathogen. The vaccine was greenlit by the FDA to prevent infection in older adults, in May. Then, around three months later, it was allowed to be administered to infants and pregnant people, crowning it the first ever maternal RSV vaccine to hit the market.
The second approval came after the vaccine was found to be successful in clinical trials. ABRYSVO was found to be effective against medically attended severe RSV-associated lower respiratory tract illness in young kids. Plus, no safety issues were detected.
That’s not all in the world of RSV vaccine development. In fact, 2023 was a major year for RSV research. It also saw the entry of AREXVY into the market. AREXVY, which is developed by global pharmaceutical GSK, became the first vaccine against RSV for older adults, back in May.
A landmark phase 3 trial found that the vaccine showed statistically significant and clinically meaningful overall efficacy of 82.6% in patients older than 60 years of age. Having met the primary endpoint, the vaccine’s efficacy was 94.6%. AREXVY is an adjuvanted vaccine that contains a recombinant subunit prefusion RSV F glycoprotein antigen (RSVPreF3) combined with GSK’s AS01E adjuvant.
An ongoing trial with the vaccine looks at preventing the disease in patients aged between 50 and 59, who are at a greater risk for being affected by RSV due to comorbidities. Early-stage results of the phase 3 trial reveal that primary endpoints were met and that the vaccine elicited an immune response. The pharmaceutical giant hopes to file for regulatory review soon.
This list is certainly not complete without mentioning CASGEVY. A watershed moment in CRISPR history, FDA gave the nod to CASGEVY, which is developed by Vertex Pharmaceuticals, CRISPR Therapeutics and Bluebird Bio, to treat sickle cell disease and beta-thalassemia.
Prior to the FDA go-ahead, the U.K. became the first company to approve the therapy. As both sickle cell disease and beta-thalassemia are caused by errors in the genes that encode for hemoglobin – the protein responsible for delivering oxygen to the tissues – this gene editing tool works by switching the gene for fetal hemoglobin on. This protein is the main oxygen carrier in the fetus.
By dialing down the BCL11A gene, which represses fetal hemoglobin, the therapy restarts the production of the protein in order to boost oxygen supply to the tissues.
But how exactly is the therapy administered? Stem cells from the blood marrow are extracted from people with sickle cell and beta-thalassemia, after which CRISPR/Cas9 is employed to edit the genes that code for hemoglobin. At the site of the BCL11A gene, the CAS9 molecular scissors cut the DNA strands. These cells are then reintroduced back into the patient, enabling the production of fetal hemoglobin to relieve disease symptoms.
This stamp of approval opens doors to cure other diseases that manifest because of faulty genes through gene editing.
A turning point in kidney research, Swedish biotech Calliditas Therapeutics’ TARPEYO has been nailed down as the only FDA-approved treatment for IgA nephropathy to significantly reduce the loss of kidney function.
Although more than two years ago, it secured accelerated approval, TARPEYO, a corticosteroid, has now made it as the first fully FDA-approved treatment to tackle the kidney disorder. IgA nephropathy is caused by the buildup of IgA antibodies in kidney tissues. TARPEYO’s mechanism of action involves reducing the protein content in the urine.
The phase 3 trial results that led to its FDA win showed that there was a 6.11 mL/min/1.73 m2 decline in estimated glomerular filtration rate (eGFR) – a measure of how well your kidneys work – in the treatment cohort compared to a 12.0 mL/min/1.73 m2 decline in the placebo group. This means that there was 50% less damage to the kidneys when patients were treated with TARPEYO as opposed to patients who were given the placebo over two years.
While this new drug may come with side effects like immunosuppression, it is said to have fewer ones than other corticosteroids because budesonide, the active ingredient in TARPEYO, is only absorbed in small amounts in the body and works in the gut.
Widening its treatment scope in immunology, pharma giant Eli Lilly finally received clearance for its ulcerative colitis drug Omvoh, in October. The delayed approval was following its success in wooing regulators in Japan and Europe.
The treatment is an interleukin-23p19 (IL-23p19) antagonist for adults with moderate to severe ulcerative colitis. This means that the drug selectively targets the p19 subunit of IL-23, which causes bowel inflammation that is linked to the disease. It took a while for the drug to prove its worth to the FDA, which was driven by phase 3 trial results. 65% of patients achieved clinical response and nearly one-fourth (24%) achieved clinical remission.
Out of the 65%, 51% of all patients and 45% of patients who failed prior treatment, attained clinical remission at one year. Omvoh also had its victory with the European Medicines Agency (EMA). But that’s not all that the multinational pharmaceutical looks to cure with the drug. Eli Lilly has plans to use it to treat Crohn’s disease, which is another inflammatory condition, as well. In a phase 3 study, the drug beat the placebo, and met primary and secondary endpoints.
J&J’s second prized possession to make it on the list, TALVEY is a humanized monoclonal antibody to target multiple myeloma. It has been granted accelerated approval by the FDA to those patients who have received at least four prior lines of therapy. TALVEY binds to the CD3 receptor expressed on the surface of T cells, activating them. This leads to the release of proinflammatory cytokines, which help kill the multiple myeloma cells.
A trial involving 187 patients found that the overall response rate was 73% in the 100 people who were administered the drug. 85% of those who responded to treatment maintained the response for at least nine months.
However, the drug does come with a boxed warning for cytokine release syndrome (CRS) and neurologic toxicity. These side effects, which can be detrimental if not treated in time, tend to come with certain cancer drugs, and are characterized by an inflammatory response.
Other drugs that caught Clarivate’s and regulators’ attention alike, include zolbetuximab, which is a monoclonal antibody designed to treat metastatic HER2-negative gastric and gastroesophageal junction (GEJ) adenocarcinoma, owned by Japanese multinational Astellas, and Welsh biotech Verona Pharma’s inhaled dual phosphodiesterase (PDE) inhibitor ensifentrine, against chronic obstructive pulmonary disease (COPD). However, the former’s Biologics License Application (BLA) was turned down by the FDA last week, citing manufacturing concerns.
Meanwhile, the partnership between Bayer and Regeneron Pharmaceuticals in developing aflibercept has been fruitful, with the drug having received the signal to treat wet age-related macular degeneration, an eye disorder that causes blurry vision. And, datopotamab deruxtecan, an antibody drug conjugate (ADC) born out of a AstraZeneca-Daiichi Sankyo collaboration, has triumphed in a phase 3 study in breast cancer, which could pave the regulatory path for an approval.