JULY 2023 CHMP POSITIVE OPINIONS
The EMA's CHMP gave a positive opinion for ViiV Healthcare's cabotegravir, marking a significant advancement in HIV prevention. Cabotegravir is the first and only long-acting injectable option for pre-exposure prophylaxis (PrEP), designed to reduce the risk of sexually acquired HIV-1.
The positive opinion is based on robust data from the HPTN 083 and HPTN 084 phase IIb/III studies. These studies demonstrated cabotegravir's superior efficacy in reducing the risk of HIV acquisition compared to the daily oral PrEP option of FTC/TDF tablets. Remarkably, cabotegravir required administration as few as six times per year to achieve these results.
HPTN 083 and HPTN 084 were international phase IIb/III multicentre, randomized, double-blind, active-controlled studies. The trials revealed that participants given cabotegravir for PrEP experienced a 69% lower rate of HIV acquisition compared to those using FTC/TDF tablets in HPTN 083 and 90% lower rate of HIV acquisition in HPTN 084.
Considering that approximately 100,000 individuals in Europe receive a new HIV diagnosis each year, the positive CHMP opinion for cabotegravir marks a significant step towards expanding HIV prevention options in the region.
Janssen Pharmaceutical received EMA's CHMP-positive recommendation for their novel bispecific antibodies, Talvey (talquetamab) and Tecvayli (teclistamab), intended for the treatment of patients with relapsed and refractory multiple myeloma (RRMM).
Talvey (talquetamab) is the first therapy targeting GPRC5D to receive a positive CHMP opinion. It is a subcutaneous bispecific antibody designed to bind G protein-coupled receptor class C group 5 member D (GPRC5D) on multiple myeloma cells and CD3 T-cells. The CHMP has recommended conditional marketing authorization for talquetamab as a monotherapy for adult patients with RRMM who have undergone at least three prior therapies.
Tecvayli (teclistamab) has also received a positive CHMP opinion for a Type II variation, proposing a reduced, biweekly dosing schedule of 1.5mg/kg every other week for patients who have achieved a complete response or better for six months or longer. Teclistamab is the first bispecific antibody targeting B-cell maturation antigen (BCMA) on myeloma cells and CD3 T-cells to be licensed in Europe for treating adult patients with RRMM who were treated with three prior treatments.
The CHMP's positive recommendations for talquetamab and teclistamab are supported by data from their respective Phase 1/2 studies, MonumenTAL-1 (talquetamab) and MajesTEC-1 (teclistamab). These studies evaluated the safety profile and efficacy of the bispecific antibodies in patients with RRMM. The latest data from both trials were presented at the ASCO 2023 Annual Meeting and the European Hematology Association (EHA) 2023 Hybrid Congress.
Merck has received a positive CHMP recommendation for gefapixant. Gefapixant is an investigational, non-narcotic, oral selective P2X3 receptor antagonist developed for the treatment of adults with refractory or unexplained chronic cough.
The CHMP's positive recommendation was based on two Phase 3 studies, COUGH-1 and COUGH-2, which are the first ever completed in patients with refractory or unexplained chronic cough. This condition refers to a persistent cough that remains despite appropriate treatment of underlying conditions or when the cause cannot be identified despite thorough evaluation. Both COUGH-1 and COUGH-2 trials met their primary endpoints, demonstrating a statistically significant reduction in 24-hour cough frequency in adults treated with gefapixant 45 mg twice daily compared to placebo at 12 weeks (COUGH-1) and 24 weeks (COUGH-2).
COUGH-1 and COUGH-2 are Phase 3 placebo-controlled trials intended to assess the efficacy and safety of gefapixant in adults with refractory chronic cough (RCC) or unexplained chronic cough (UCC). The trials involved a total of 2,044 participants, with 730 in COUGH-1 and 1,314 in COUGH-2. Participants were randomly assigned to receive either gefapixant 45 mg twice daily, 15 mg twice daily, or placebo.
The primary efficacy outcomes were 24-hour cough frequency at week 12 (COUGH-1) and 24-hour cough frequency at week 24 (COUGH-2), measured using an ambulatory digital audio recording device. In the COUGH-1 study, 24-hour cough frequency at 12 weeks was reduced by 18.45% versus placebo; in the COUGH-2 study, at 24 weeks, cough frequency was reduced by 14.64% versus placebo. However, the treatment arms receiving gefapixant 15 mg twice daily did not meet the primary efficacy endpoint in either Phase 3 study.
Secondary endpoints included awake cough frequency and the percentage of participants with a significant increase in the Leicester Cough Questionnaire (LCQ) total score from baseline.
Previously in January 2022, FDA rejected the approval of gefapixant in the US.
AbbVie received a positive CHMP recommendation for the conditional marketing authorization of Tepkinly (epcoritamab) as a monotherapy for diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy who are in a relapsed or refractory state. If approved, epcoritamab will be the first and only subcutaneous bispecific antibody conditionally approved for this indication in Europe for adults.
The final decision by the European Commission is expected later this year.
The positive opinion was based on the EPCORE NHL-1 Phase 1/2 trial, an open-label trial evaluating the efficacy and safety of epcoritamab in patients with non-Hodgkin's lymphoma (NHL), including DLBCL. DLBCL is an aggressive subtype of NHL, accounting for approximately 30 per cent of all global cases.
The primary endpoint of the EPCORE NHL-1 trial was the overall response rate, as assessed by an independent review committee, which was found to be 63.1%.
EPCORE NHL-1 is a multi-centre study comprising a Phase 1 first-in-human dose escalation part, a Phase 2a expansion part, and a dose optimization part. The trial also explored secondary efficacy endpoints, such as overall survival, progression-free survival and complete response rate. The most common treatment-emergent adverse events included cytokine release syndrome, pyrexia, and fatigue.
AbbVie has received a favorable opinion from the Committee for Medicinal Products for Human Use for its drug atogepant. If approved by the European Commission (EC), atogepant will become the first and only once-daily oral calcitonin gene-related peptide (CGRP) receptor antagonist in the European Union (EU) for the preventive treatment of migraines in adults who experience at least four migraine days per month.
The positive recommendation is based on the results of two Phase 3 clinical trials, PROGRESS and ADVANCE, which evaluated the efficacy of atogepant in adults with episodic or chronic migraines.
Chronic migraine is defined as experiencing 15 or more headache days per month, with at least eight migraines. On the other hand, episodic migraine refers to individuals with fewer than 15 headache days per month.
Migraine has a significant economic impact, costing the European economy an estimated €50 billion annually due to reduced productivity and lost workdays.
The positive CHMP opinion is based on data from PROGRESS and ADVANCE trials, which both demonstrated a reduction in monthly migraine days compared to a placebo over a 12-week treatment period.
In the Phase 3 PROGRESS study, the mean monthly migraine days change from baseline was −6.8 days for atogepant 60 mg QD and -5.1 days for placebo. In the ADVANCE study, the change in MMDs was -4.1 days for atogepant 60 mg QD versus -2.5 months in patients on placebo.
Migraine is a highly prevalent condition, affecting approximately 1 billion people worldwide, including an estimated 41 million in Europe. Migraine attacks can be debilitating, hindering daily activities and significantly impacting the quality of life.
Atogepant, an orally administered CGRP receptor antagonist, explicitly targets the preventive treatment of migraines in adults with at least four migraine days per month. CGRP and its receptors play a role in migraine pathophysiology, with elevated CGRP levels observed during migraine attacks. Clinical studies have demonstrated the clinical benefit of selective CGRP receptor antagonists in treating migraines.
The CHMP issued a positive opinion, recommending the approval of Jesduvroq (daprodustat) as a treatment for symptomatic anaemia in adults with chronic kidney disease undergoing chronic dialysis.
Jesduvroq will be made available in the form of film-coated tablets. Its active ingredient, daprodustat, is administered orally and acts as an anti anaemic agent. Daprodustat works by inhibiting hypoxia-inducible factor (HIF)-prolyl hydroxylase, which stimulates erythropoietin production. This process leads to increased mobilization of iron and the production of haemoglobin and red blood cells.
The primary advantage of Jesduvroq is its ability to correct haemoglobin levels in patients on dialysis, yielding effects similar to those observed with erythropoiesis-stimulating agents. The most common adverse events were hypertension, thromboembolic events, and diarrhoea.
EXTENSION OF INDICATION
Imjudo, a promising medication for the treatment of non-small cell lung cancer (NSCLC), has taken a significant step towards approval in the European Union. The Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion, recommending granting marketing authorization for Imjudo.
Imjudo is specifically intended for treating patients with advanced or metastatic NSCLC as a first-line treatment and in patients with no sensitizing EGFR mutations or ALK-positive mutations. This positive opinion from CHMP signifies the potential efficacy and safety of Imjudo, leading to a potential breakthrough in managing this devastating disease.
Gilead received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) for its drug Trodelvy (sacituzumab govitecan) in the treatment of pre-treated hormone receptor-positive (HR+), HER2-negative metastatic breast cancer. This recommendation is based on the TROPiCS-02 study, which demonstrated that Trodelvy significantly improved overall survival compared to a physician's choice of chemotherapy.
The positive CHMP opinion is supported by the Phase 3 TROPiCS-02 study, which showed that Trodelvy provided a statistically significant and clinically meaningful overall survival benefit. Overall survival was improved by 3.2 months; the median overall survival was 14.4 months in the Trodelvy arm versus 11.2 months in patients with the physician's choice of chemotherapy. Treatment with Trodelvy reduced the risk of disease progression or death by 34%, with a median progression-free survival of 5.5 months compared to 4.0 months with chemotherapy.
The study also revealed other positive outcomes, including improved objective response rate and time to deterioration in quality of life. However, there was no statistically significant difference in the time to worsening of the pain scale.
The CHMP positive opinion for Trodelvy represents a significant step in expanding treatment options for patients with pre-treated HR+/HER2- metastatic breast cancer in Europe. The drug has demonstrated its ability to improve overall survival and progression-free survival, offering hope for those in need of effective therapies.
Jardiance, a medication containing empagliflozin, has received a positive recommendation from the Committee for Medicinal Products for Human Use (CHMP) for the treatment of adults with chronic kidney disease (CKD). This recommendation is based on the findings of the EMPA-KIDNEY trial, which is the largest and most comprehensive study to date involving SGLT2 inhibitors in CKD patients.
If approved, Jardiance could significantly improve the standard of care for over 47 million European Union individuals living with CKD and other interconnected cardio-renal-metabolic conditions. Currently, empagliflozin is indicated for treating heart failure and type 2 diabetes in adults. However, this positive recommendation from CHMP would expand its indications to include adults with CKD, offering a comprehensive approach to managing the increased risks associated with cardio-renal-metabolic conditions.
The EMPA-KIDNEY Phase III trial involved 6,609 adults with varying degrees of CKD severity and a wide range of underlying causes and co-morbidities. It is the most extensive and inclusive dedicated trial for SGLT2 inhibitors in CKD patients thus far. The trial demonstrated that empagliflozin significantly benefits kidney function and cardiovascular health in adults with CKD. Compared to the placebo group, empagliflozin reduced the relative risk of kidney disease progression or cardiovascular death by 28 percent.
Amicus Therapeutics' Opfolda (miglustat) received a positive recommendation from the Committee for Medicinal Products for Human Use (CHMP) to treat Late-Onset Pompe Disease.
The European Commission approval is anticipated in the third quarter of 2023. Opfolda is given in combination with Pombiliti (cipaglucosidase alfa). The company stated that once the approval of Opfolda is received, the drug will be available as a combination with Pombiliti.
Opfolda is an enzyme stabilizer given in combination with long-term enzyme replacement therapy, Pombiliti (cipaglucosidase alfa).
The approval was based on the Phase 3 PROPEL pivotal study, a randomized trial in LOPD patients who are ERT-naive and ERT-experienced.
Roche announced that the CHMP recommended approving Columvi (glofitamab) to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) post two or more lines of therapy.
The approval was based on the Phase I/II NP30179 study, demonstrating the efficacy in patients with R/R DLBCL. Results showed that Columvi given as a fixed course had induced a complete response (CR) in 35.2% of people and an overall response (OR) in 50% of people. Within patients who achieved CR, 74.6% of patients had experienced a response at 12 months. The duration of the response still needs to be reached.
The common adverse events are cytokine release syndrome, neutropenia, anemia, and thrombocytopenia.
Bristol Myers Squibb (BMS) received CHMP positive opinion for CAMZYOS (mavacamten) to treat symptomatic obstructive hypertrophic cardiomyopathy (HCM).
The positive recommendation was based on two Phase 3 trials, EXPLORER-HCM and VALOR-HCM.
The Phase 3 EXPLORER-HCM trial evaluated efficacy in patients with symptomatic obstructive HCM. The Phase 3 VALOR-HCM study was conducted in patients with symptomatic obstructive HCM who met the 2011 ACC/AHA or 2014 ESC guideline criteria. The drug met all the primary and secondary endpoints in both studies.
GlaxoSmithKline's (GSK) vaccine candidate for the respiratory syncytial virus (RSV) in older adults has received a positive opinion from the CHMP.
The vaccine candidate, known as RSVPreF3, is a protein-based vaccine that targets RSV, a common respiratory virus that can cause serious illness in older adults. The vaccine is designed to trigger an immune response that protects against RSV infection.
The positive CHMP opinion is based on data from a Phase III trial that demonstrated the vaccine's safety and efficacy in preventing RSV-associated lower respiratory tract infections in older adults. In the pivot trial, the vaccine reduced severe disease in 94.1% of the population, and the overall efficacy was 82.6%.
EXTENSION OF INDICATION
Novartis announced that its drug Cosentyx (secukinumab) had received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) for the treatment of moderate-to-severe hidradenitis suppurativa (HS).
The positive CHMP opinion was based on data from two Phase III clinical trials, SUNSHINE and SUNRISE. There was an improvement in the Hidradenitis Suppurativa Clinical Response (HiSCR); there was an improvement at Week 16, and it was sustained in more than 55% of patients at Week 52.
The safety findings were consistent with the existing safety profile of Cosentyx. The drug is expected to receive approval in the US later this year.
UCB announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended granting marketing authorization for bimekizumab in the European Union (EU) for the treatment of adults with active axial spondyloarthritis (axSpA) and active psoriatic arthritis (PsA).
Positive results from four Phase 3 clinical studies in PsA and axSpA showed that treatment with bimekizumab consistently resulted in deep levels of response that were rapid and sustained.
In active PsA, the CHMP recommended approval of bimekizumab alone or in combination with methotrexate for adults who have had an inadequate response or who have been intolerant to one or more disease-modifying antirheumatic drugs. The CHMP recommended approval of bimekizumab for treating adults with axial spondyloarthritis.
The positive recommendation was based on BE COMPLETE and BE OPTIMAL trials for psoriatic arthritis and BE MOBILE 1 and BE MOBILE 2 for active axial spondyloarthritis. In all the studies, the primary and secondary endpoints were met.
Bimekizumab is a monoclonal antibody that inhibits IL-17A and IL-17F, two cytokines involved in inflammatory processes that contribute to the development and progression of these conditions.
FEBRUARY 2023 CHMP POSITIVE OPINIONS
Akeega received CHMP positive opinion for adult patients with BRCA1/2-metastatic castration-resistant prostate cancer.
The CHMP gave a positive opinion for Akeega (niraparib and abiraterone acetate) to treat adult patients with BRCA1/2-mutated metastatic castration-resistant prostate cancer.
The CHMP positive opinion was based on the Phase 3 MAGNITUDE study; Akeega demonstrated significant improvement in radiographic progression-free survival versus standard of care. After a median follow-up of 24.8 months, the median rPFS was 19.5 months versus 10.9 months in patients on placebo.
Prostate cancer is the most common cancer in Europe, and Akeega is a highly selective polyadenosine diphosphate-ribose polymerase (PARP) inhibitor. Along with abiraterone acetate, Akeega targets two oncogenic mutations.
Incyte's Opzelura received a positive opinion for non-segmental vitiligo in adults and adolescents.
Incyte announced the positive CHMP opinion for its non-segmental vitiligo treatment Opzelura (ruxolitinib cream). It is approved for treating adults and adolescents for repigmentation in non-segmental vitiligo.
The approval was based on TRuE-V1 and TRuE-V2, evaluating the efficacy of Opzelura versus placebo in more than 600 people aged 12 years and older. There is a significant improvement in the facial and total body repigmentation versus placebo in terms of reaching the facial and total body Vitiligo Area Scoring Index (F-VASI-T-VASI) endpoints at Week 24.
The common adverse events are acne, nasopharyngitis, headache, and urinary tract infection.
Vafseo received CHMP positive opinion for symptomatic anemia associated with chronic kidney disease in adults.
Vafseo (vadadustat), an oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, received positive CHMP opinion for treating anemia associated with chronic kidney disease in adults on chronic maintenance dialysis.
The approval was based on INNO2VATE studies demonstrating the non-inferiority of vadadustat versus darbepoetin alfa. The primary endpoint was a change in hemoglobin between the baseline and primary evaluation period.
In the incident dialysis-dependent chronic kidney disease (DD-CKD) patients, the change in hemoglobin concentration was -0.31g/dl at weeks 24 to 36. In prevalent dialysis-dependent chronic kidney disease (DD-CKD) patients, the difference is -0.17 g/dl.
Vafseo was proved to be non-inferior to darbepoetin alfa regarding safety and efficacy.
EXTENSION OF INDICATION
Rinvoq received CHMP positive opinion for moderate to severe Crohn's disease.
AbbVie announced that the CHMP recommended the approval of Rinvoq (upadacitinib) for moderate to severely active Crohn's disease. The positive recommendation was based on two induction studies, U-EXCEED and U-EXCEL, and one maintenance study, U-ENDURE.
AbbVie announced that a significant number of patients achieved clinical remission and endoscopic response from baseline versus placebo. Also, a significant number of patients achieved endoscopic remission, a secondary endpoint.
The safety profile was consistent with the existing safety profile of Rinvoq.
CHMP gave a negative recommendation for Merck's molnupiravir for patients diagnosed with COVID-19.
The CHMP gave a negative recommendation for Merck's Lagevrio (molnupiravir) for treating adult patients with COVID-19 infection. Merck and Ridgeback announced that they would request for re-examination.
The negative recommendation was based on the Phase 3 MOVe-OUT trial and real-world evidence.
Merck generated $5.7 billion in revenues in 2022.
JANUARY 2023 CHMP POSITIVE OPINION
BMS's Sotyktu received CHMP's positive opinion for psoriasis.
The Committee for Medicinal Products for Human Use (CHMP) recommended the approval of Sotyktu (deucravacitinib) for treating adult patients with moderate-to-severe plaque psoriasis.
The positive recommendation was based on the Phase 3 POETYK PSO-1 and POETYK PSO-2 trials, demonstrating the efficacy versus placebo and Otezla.
In the POETYK PSO-1 trial, the Psoriasis Area and Severity Index (PASI 75) and static Physician's Global Assessment score of 0 or 1 (sPGA 0/1) were the primary endpoints. In patients on Sotyktu, PASI75 at week 16 was 58.4% versus 35.1% in patients on Otezla. sPGA 0/1 was 53.6% in the Sotkyu arm versus 32.1% in patients on Otezla.
In the POETYK PSO-2 trial, PASI 75 was 53.0% on Sotkyu versus 39.8% on Otezla; sPGA 0/1 was 49.5% on Sotkyu versus 33.9% on patients on Otezla.
Sotyktu is the allosteric tyrosine kinase 2 (TYK2) inhibitor approved previously in the US for psoriasis. Sotkyu demonstrated superiority over Otezla and was well tolerated.
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