November 15, 2023
FDA Gives Nod to Augtyro for Advanced ROS1-Positive Non-Small Cell Lung Cancer
Bristol Myers Squibb has received approval from the US Food and Drug Administration (FDA) for Augtyro (repotrectinib), a next-generation tyrosine kinase inhibitor (TKI), designed for the treatment of adults with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC). The oral therapy, administered as a TKI targeting ROS1 oncogenic fusions, strengthens Bristol Myers Squibb’s position in precision medicine for NSCLC.
The FDA's decision is rooted in the success of the TRIDENT-1 study, a Phase 1/2 trial assessing Augtyro's efficacy in both TKI-naïve and TKI-pretreated patients. For TKI-naïve patients (n=71), the primary endpoint of objective response rate (ORR) was an impressive 79%, with a median duration of response (mDOR) reaching 34.1 months. In the TKI-pretreated group (n=56), the ORR was 38%, and the mDOR stood at 14.8 months. Notably, responses in intracranial lesions were observed among patients with measurable CNS metastases at baseline.
TRIDENT-1, a global Phase 1/2 trial, delves into the safety, tolerability, pharmacokinetics, and anti-tumor activity of repotrectinib in patients with advanced solid tumors, including NSCLC harboring ROS1 fusions. The ongoing trial, which allows asymptomatic CNS metastases, is still under analysis, excluding symptomatic brain metastases. Phase 1 established the recommended Phase 2 dose, while Phase 2 focuses on overall response rate (ORR) as the primary endpoint.
Augtyro's FDA-approved dosing involves 160 mg orally once daily for the initial 14 days, followed by an increase to 160 mg twice daily until disease progression or unacceptable toxicity.
October 31, 2023
FDA Approves Cosentyx for Treating Hidradenitis Suppurativa in Adults
The US Food and Drug Administration (FDA) have given its approval for the use of Cosentyx in treating adult patients with moderate to severe hidradenitis suppurativa (HS). Cosentyx, an interleukin-17A (IL-17A) inhibitor, targets the cytokine responsible for the inflammation associated with HS.
This approval was based on the findings from the SUNSHINE and SUNRISE trials. These trials indicated that administering Cosentyx at intervals of every two weeks or four weeks led to a Hidradenitis Suppurativa Clinical Response (HiSCR50) compared to a placebo.
The onset of action was noticeable as early as Week 2 and continued to show improvement up to Week 16, with sustained positive effects observed through the 52 weeks in the clinical trials.
Additionally, the safety profile of Cosentyx remained consistent with its existing safety standards, ensuring a similar safety profile during the trials.
October 26, 2023
FDA approved Lilly's IL-23p19 inhibitor, Omvoh for ulcerative colitis
Lilly announced that the US FDA approved interleukin-23p19 (IL-23p19) inhibitor, Omvoh (mirikizumab) for ulcerative colitis. The drug is indicated for moderate to severe disease.
The approval was based on the LUCENT program, a double-blind, placebo-controlled Phase 3 clinical trials. The induction study includes a 12-week trial followed by a 40-week maintenance phase. Patients who were previously treated with biologics were included in the trial.
After the induction treatment, 65% of patients on Omvoh and 43% of patients on placebo achieved clinical response. 24% of patients on Omvoh and 15% of patients on placebo achieved clinical remission.
In patients who exhibited a clinical response at the 12-week mark, Omvoh consistently showed effectiveness across various subgroups. Comparatively, 51% of all patients and 45% of those who had previously not responded to treatment with a biologic or Janus kinase inhibitor (JAKi) achieved clinical remission after one year, in contrast to the placebo group, where the rates were 27% and 15%, respectively. Furthermore, among individuals who responded to treatment at the 12-week mark, half (50%) achieved a state of clinical remission without the need for steroids at one year, as opposed to 27% in the placebo group.
Rectal bleeding and stool frequency were the common adverse events.
September 23, 2023
FDA Approved Jardiance for CKD Progression Risk Reduction
The Food and Drug Administration (FDA) approved Jardiance (empagliflozin) 10 mg tablets in the treatment of adults facing chronic kidney disease (CKD). This approval presents an addition to the array of treatments accessible to the over 35 million adults grappling with CKD in the United States.
Boehringer Ingelheim and Eli Lilly, in collaboration, have announced the latest FDA approval. The FDA has officially authorized Jardiance (empagliflozin) 10 mg tablets to reduce the risk of sustained declines in estimated glomerular filtration rate (eGFR), end-stage kidney disease, cardiovascular mortality, and hospitalization in adults at risk of CKD progression.
The EMPA-KIDNEY phase III trial has confirmed the effectiveness of Jardiance 10 mg tablets in reducing the risk of kidney disease progression. Notably, EMPA-KIDNEY is the first CKD trial involving an SGLT2 inhibitor to demonstrate a statistically significant reduction in initial and recurrent hospitalisation risk in adults with CKD.
The EMPA-KIDNEY trial was designed to encompass a diverse group of adults with CKD, whether or not they had type 2 diabetes. Over 6,600 patients were enrolled following the trial's inclusion and exclusion criteria. Patients included in the study had an eGFR ranging from ≥20 to <45 mL/min/1.73 m2 or an eGFR between ≥45 and <90 mL/min/1.73 m2, coupled with a urine albumin to creatinine ratio of ≥200 mg/g.
In the EMPA-KIDNEY trial, Jardiance exhibited a noteworthy 28% relative risk reduction (equating to an absolute risk reduction of 3.6% per patient-year at risk) compared to a placebo, both administered with standard care. This reduction was observed for the composite primary endpoint. The event rate for patients receiving Jardiance was 13.1%, while for those on placebo, it stood at 16.9%. Importantly, EMPA-KIDNEY is the inaugural SGLT2 inhibitor CKD trial to substantially reduce the risk of initial and recurrent hospitalisation, a pre-defined critical secondary endpoint. Jardiance displayed a 14% relative risk reduction in this regard, with the Jardiance group experiencing 1,611 hospitalisations among 960 patients (24.8 events per 100 patient-years), compared to the placebo group, where 1,895 hospitalisations occurred among 1,035 patients (29.2 events per 100 patient-years).
This achievement marks the fourth FDA approval for Jardiance from the EMPOWER program. With a global enrollment of more than 700,000 adults across clinical trials, the EMPOWER program underscores the enduring commitment of the Boehringer Ingelheim and Lilly Alliance to enhancing outcomes for individuals grappling with cardio-renal-metabolic conditions.
Ojjaara (momelotinib) has received approval in the United States as a groundbreaking treatment option for individuals suffering from anaemia in myelofibrosis patients. This marks a significant milestone in addressing a critical medical need among myelofibrosis patients.
The approval encompasses using Ojjaara for myelofibrosis patients dealing with anaemia, regardless of whether they have previously undergone myelofibrosis therapy. This development is particularly noteworthy because a large majority of myelofibrosis patients are anticipated to develop anaemia during the progression of their disease. Alarmingly, more than 30% of these patients have had to discontinue their treatments due to the onset of anaemia.
Ojjaara, an oral medication taken once daily, belongs to a unique class of drugs known as JAK1/JAK2 and activin A receptor type 1 (ACVR1) inhibitors. It is currently the sole FDA-approved medicine designed to cater to newly diagnosed myelofibrosis patients and those who have undergone previous treatments, all while effectively addressing the primary symptoms of the disease, namely anaemia, constitutional symptoms, and splenomegaly (enlarged spleen).
The FDA's decision to approve momelotinib is firmly grounded in data from the pivotal MOMENTUM study and a subgroup of adult patients suffering from anaemia who participated in the SIMPLIFY-1 phase III trial. The MOMENTUM study was meticulously designed to assess the safety and efficacy of momelotinib compared to danazol for treating and mitigating key manifestations of myelofibrosis among patients who were symptomatic and experienced with JAK inhibitors.
The primary endpoint in the MOMENTUM trial is the TSS response at week 24; the Total Symptom Score (TSS) response was defined as Myelofibrosis Symptom Assessment Form (MFSAF) v4.0. The MOMENTUM trial achieved all its primary and critical secondary endpoints, demonstrating statistically significant improvements in constitutional symptoms, splenic response, and transfusion independence in patients treated with momelotinib instead of those treated with danazol. SIMPLIFY-1, on the other hand, aimed to evaluate momelotinib's efficacy and safety compared to ruxolitinib in myelofibrosis patients who had not been previously exposed to JAK-inhibitor therapy. The safety and efficacy findings for SIMPLIFY-1 were primarily based on a subgroup of patients dealing with anaemia.
One of the distinguishing features of Ojjaara is its unique mechanism of action, which involves inhibiting three pivotal signalling pathways: Janus kinase (JAK) 1, JAK2, and activin A receptor, type I (ACVR1).
The US Food and Drug Administration (FDA) approved Regeneron Pharmaceuticals' Veopoz (pozelimab) for treating adults and pediatric patients aged one year and above who suffer from CHAPLE disease, scientifically known as CD55-deficient protein-losing enteropathy. Notably, this accomplishment is the 10th FDA-approved medication developed by Regeneron.
CHAPLE disease is an extremely rare hereditary ailment characterized by potential life-threatening symptoms in the gastrointestinal and cardiovascular systems. The disease is fueled by excessive activation of the complement system, a crucial mechanism for neutralizing microbes in the body. In CHAPLE patients, due to mutations in the CD55 gene, the complement system's activity cannot be adequately regulated. Consequently, this can lead to the complement system attacking healthy cells, causing damage to blood and lymph vessels along the upper digestive tract. This results in the loss of circulating proteins. Notably, the prevalence of CHAPLE disease in the US is minimal, with fewer than ten identified patients.
Veopoz, a fully human monoclonal antibody, is ingeniously designed to target complement factor C5, an essential protein initiating complement system activation. However, it's worth highlighting that using complement inhibitors, like Veopoz, has been associated with severe and even fatal meningococcal infections in patients. Prompt recognition and treatment are vital in such cases to avert life-threatening consequences. To mitigate this risk, individuals scheduled for Veopoz treatment should undergo complete or updated meningococcal vaccination at least two weeks before receiving the first dose. Urgent therapy should be accompanied by meningococcal vaccination and antibacterial drug prophylaxis in patients not up-to-date with the recommended vaccinations.
The approval of Veopoz by the FDA is based on the findings of a Phase 2/3 open-label clinical trial. The trial involved ten patients ranging from 3 to 19 years of age, with a median age of 8.5 years. Participants were administered an initial loading dose of pozelimab 30 mg/kg intravenously on the first day, followed by weekly subcutaneous doses based on weight. Encouragingly, all ten patients experienced the normalization of serum albumin and serum IgG concentrations within 12 weeks and maintained these levels for at least 72 weeks during the treatment course. The trial data demonstrated notable reductions in albumin transfusions and hospitalizations, indicating the positive impact of Veopoz on the patients' health. Before commencing treatment, five out of the ten patients underwent a collective total of 60 albumin transfusions over a span of 48 weeks. Following the initiation of treatment, only one patient required an albumin transfusion within the subsequent 48 weeks. In the 48 weeks leading up to treatment, nine out of ten patients were admitted to the hospital, accounting for a combined duration of 268 days. In contrast, during the 48 weeks post-treatment initiation, two patients experienced hospitalizations, which totalled seven days.
Common adverse reactions reported in multiple patients included upper respiratory tract infections, fractures, urticaria (hives), and alopecia (hair loss). Veopoz, developed using Regeneron's proprietary VelocImmune technology, is a fully human monoclonal antibody strategically designed to counteract the activity of complement factor C5, thereby preventing diseases influenced by the complement pathway. It is an IgG4 antibody that binds effectively to both regular and variant forms of human C5.
As part of its continuous development efforts, Veopoz is also undergoing evaluation in combination with Alnylam's cemdisiran (a siRNA C5 inhibitor) as a combined therapy for other disorders mediated by the complement system, such as paroxysmal nocturnal hemoglobinuria (PNH) and myasthenia gravis (MG). This combination therapy is presently undergoing clinical development and has yet to be assessed for safety and efficacy by regulatory authorities.
Janssen Pharmaceutical announced the approval of Talvey (talquetamab) by the Food and Drug Administration (FDA). This novel bispecific therapy has received accelerated approval for treating refractory or relapsed multiple myeloma patients who have undergone at least four prior lines of therapy. The FDA's decision for this indication is based on the therapy's response rate and the durability of the response. However, the ongoing approval for this use depends on confirming clinical benefits in subsequent trials.
Talvey is classified as a bispecific T-cell-engaging antibody. It binds to both the CD3 receptor on T cells and the G protein-coupled receptor class C group 5 member D (GPRC5D) found on the surface of multiple myeloma cells. It also targets non-malignant plasma cells and normal tissue, including epithelial cells in keratinized tissues such as the skin and tongue. The treatment protocol for Talvey involves a weekly or biweekly subcutaneous injection after an initial step-up phase. This flexibility enables healthcare providers to tailor the treatment plan to each patient's needs.
The Phase 2 clinical trial, MonumenTAL-1, assessed Talvey's efficacy. The study included 187 patients who had experienced at least four prior lines of therapy and had not been exposed to T-cell redirection therapy. The results demonstrated promising overall response rates (ORR). In the group receiving a biweekly subcutaneous dose of 0.8 mg/kg, 73.6 per cent of patients achieved an ORR. After a follow-on of six months, 58% achieved a very good partial response (VGPR), and 33% achieved a complete response (CR) or better.
For patients on a weekly subcutaneous dose of 0.4 mg/kg, the ORR was 73.0%. After a median follow-up of 14 months, 57% achieved VGPR or better, including 35% with CR or better. The response duration was considerable, with a median not reached for the biweekly dose group and 9.5 months for the weekly dose group. Furthermore, approximately 85% of responders on the biweekly dose maintained their response for at least nine months.
In the same MonumenTAL-1 trial, 32 patients who had received prior bispecific antibody or CAR-T cell therapy (mostly B-cell maturation antigen [BCMA]-directed therapy) were treated with Talvey at a weekly subcutaneous dose of 0.4 mg/kg. With a median follow-up of 10.4 months, 72% of these patients achieved an ORR as evaluated by an Independent Review Committee. Among responders, an estimated 59 percent maintained their response for at least nine months.
Despite its potential benefits, Talvey is associated with several safety concerns. The therapy comes with cytokine release syndrome (CRS) and neurologic toxicity, which includes immune effector cell-associated neurotoxicity syndrome (ICANS).
Pfizer has received approval from the U.S. Food and Drug Administration (FDA) for Litfulo (ritlecitinib), an oral treatment for severe alopecia areata in patients aged 12 and above.
Litfulo is the first and only FDA-approved medication for adolescents with this condition. The recommended dose is 50 mg, administered once daily. Clinical trials, such as the ALLEGRO Phase 2b/3 trial involving 718 patients from 18 countries, demonstrated the efficacy and safety of Litfulo. After six months of treatment, 23% of patients on LITFULO 50 mg achieved 80% or more scalp hair coverage, compared to 1.6% on placebo. The study also confirmed consistent results for both adolescents and adults.
The most commonly reported adverse events with Litfulo were headache, diarrhoea, acne, rash, and urticaria.
The Food and Drug Administration (FDA) has given the green light for Rinvoq (upadacitinib) to be a therapy for adults who suffer from moderately to severely active Crohn's disease and have not responded adequately or are intolerant to one or more TNF blockers. This latest approval adds to Rinvoq's existing indications, as it is already approved for treating ulcerative colitis.
The FDA's decision to approve Rinvoq for Crohn's disease is supported by data from two induction studies, U-EXCEED and U-EXCEL, and the U-ENDURE maintenance study. These clinical trials demonstrated the statistical significance of Rinvoq in achieving the co-primary endpoints and key secondary endpoints compared to using a placebo. In the induction studies, it was found that 34% and 46% of patients treated with Rinvoq 45 mg achieved a significant endoscopic response at week 12, compared to only 3% and 13% of patients in the placebo group. Similarly, in the maintenance study, 28% and 41% of patients treated with Rinvoq 15 mg and 30 mg, respectively, achieved endoscopic response at week 52, while the placebo group showed a response rate of only 7%.
Furthermore, the induction studies also showed promising results in terms of clinical remission. It was observed that 36% and 46% of patients treated with Rinvoq 45 mg achieved remission at 12 weeks, in contrast to 18% and 23% of patients in the placebo group. In the maintenance trial, Rinvoq continued to exhibit efficacy, with 42% and 55% of patients treated with Rinvoq 15 mg and 30 mg, respectively, achieving clinical remission at 52 weeks, compared to 14% in the placebo group.
AbbVie aims to position Rinvoq and Skyrizi as replacements for the revenue generated by Humira, its blockbuster drug.
AbbVie announced the US Food and Drug Administration approved Epkinly (epcoritamab) for treating adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Roche's Columvi (glofitamab) was under FDA review for the same target population.
The approval was based on the Phase 1/2 EPCORE trial, which included patients with DLBCL, 86% of patients with DLBCL NOS. The patients were previously treated with a median of three therapies; 30% received two prior treatments, 30% received three, and 40% received four or more prior therapies.
The overall response is 61%, 38% of patients have a complete response rate, and the median duration of response is 15.6 months in heavily pretreated R/R DLBCL patients.
The drug has a black-box warning for severe or life-threatening cytokine release syndrome (CRS).
DLBCL is a type of non-Hodgkin's lymphoma, a cancer that affects the lymphatic system. It is an aggressive form of lymphoma that often requires additional treatment options when standard therapies are ineffective or the disease returns.
Epkinly is a bispecific antibody that targets two specific proteins, CD20 and CD3, which are present on the surface of cancerous B-cells and T-cells, respectively.
The Food and Drug Administration approved the first topical gene therapy, Vyjuvek, to treat wounds in patients with dystrophic epidermolysis bullosa (DEB), a rare and debilitating genetic skin disorder.
DEB is characterized by fragile skin prone to blistering, leading to chronic wounds and severe pain. The approved topical gene therapy utilizes a modified virus to deliver a functional COL7A1 gene directly to the patient's skin cells. The COL7A1 gene is responsible for producing a protein called type VII collagen, which helps anchor the skin's layers together.
Clinical trials conducted to evaluate the therapy demonstrated promising results. The efficacy and safety of Vyjuvek were shown in a placebo-controlled trial, recruiting 31 patients with DEB, including thirty patients with RDEB and one subject with DDEB. In the trial, two DEB wounds of the same size were considered; sixty-five percent of patients on Vyjuvek had complete closure versus 26% of patients on placebo.
The therapy targets the root cause of DEB by promoting the production of functional type VII collagen, thus enhancing the integrity of the skin.
This groundbreaking approval offers new hope for individuals living with DEB, as it addresses a critical unmet medical need. The drug has received Orphan and FastTrack designations.
The FDA's approval of the first topical gene therapy for DEB marks a significant milestone in the field of gene therapies. It highlights the potential of genetic interventions to address rare and challenging diseases.
GlaxoSmithKline (GSK) has announced that the US Food and Drug Administration (FDA) has approved its respiratory syncytial virus (RSV) vaccine, Arexvy, for the prevention of RSV disease in adults aged 65 years and older.
Arexvy is the first RSV vaccine approved for use in this age group, and is designed to help protect against RSV infections that can lead to serious respiratory illness, hospitalization, and even death.
The approval is based on data from a Phase 3 clinical trial, which showed that Arexvy significantly reduced the incidence of RSV-associated lower respiratory tract infections in adults of age 65 years and older compared to placebo.
Regeneron Pharmaceuticals and Sanofi announced that Kevzara (sarilumab) is approved by the US Food and Drug Administration for polymyalgia rheumatica (PMR). It is indicated for patients with an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper.
The approval was based on the SAPHYR Phase 3 randomized. Patients were randomized to either Kevzara 200 mg every two weeks or a placebo. After 52 weeks, Kevzara met the primary endpoint; 28% of patients on Kevzara achieved sustained remission versus 10% of patients on placebo.
Kevzara was approved under Priority Review by the US Food and Drug Administration. Kevzara was previously approved for moderately to severely active rheumatoid arthritis.
Gilead announced that the US Food and Drug Administration approved Trodelvy (sacituzumab govitecan) for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients who were previously treated with endocrine therapy and two additional systemic therapies.
The approval was based on Phase 3 TROPiCS-02, in which Gilead demonstrated significant progression-free survival and overall survival. Trodelvy demonstrated a median overall survival of 14.4 months versus 11.2 months in patients on chemotherapy. The median progression-free survival was 5.5 months versus 4.0 months, showing an improvement of 34% reduction in disease progression or death.
The safety profile was consistent with the established profile of Trodelvy.
The National Comprehensive Cancer Network preferred Trodelvy as a treatment option for HR+/HER2-negative breast cancer.
GSK announced that the US Food and Drug Administration (FDA) approved Jesduvroq (daprodustat) for treating adult patients with chronic kidney disease (CKD). Jesduvroq was a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), a new oral treatment approved for anemia in CKD patients in over 30 years.
The approval was based on the ASCEND-D trial, a randomized open-label Phase 3 trial. The primary endpoint was hemoglobin levels from baseline to week 28 to week 52 and the first occurrence of major cardiovascular events. The mean change in the hemoglobin level from baseline to week 28 through 52 weeks was 0.28±0.02 g/deciliter in Jesduvroq versus 0.10±0.02 g/deciliter in the epoetin alfa group. After the median follow-up of 2.5 years, cardiovascular events were observed in 25.2% of Jesduvroq patients versus 26.7% in the ESA group.
The regulatory approval was under review with the European Medicines Agency. In Japan, it was approved in June 2020 for treating patients with anemia of CKD.
Merck has announced that the US Food and Drug Administration (FDA) approved Keytruda (pembrolizumab) as an adjuvant treatment after surgery and platinum-based chemotherapy. It is approved in patients with stage IB, II, or IIIA non-small cell lung cancer (NSCLC).
The FDA approval was based on the KEYNOTE-091 trial, in which Keytruda demonstrated improvement in disease-free survival versus placebo in NSCLC patients following surgical resection and platinum-based chemotherapy. This is the fifth indication in the NSCLC setting and the 34th overall indication in the US.
In the Phase 3 KEYNOTE-091 trial, investigator-assessed disease-free survival (DFS) is the primary endpoint. Keytruda reduced the risk of disease recurrence or death by 27% versus the placebo. The median DFS was 58.7 months in patients on Keytruda versus 34.9 months in patients on placebo.
Merck announced the safety profile in the KEYNOTE-091 trial is consistent with the existing one.