CLINSQUARE: CLINICAL RESEARCH COURSES
Wednesday, February 12, 2025
CLINSQUARE: Clinical Rsearch Courses by LIFEPRONOW
Home Blog Page 110

Pfizer and Sangamo announced results of its gene therapy for severe hemophilia A

admin
-
0
Pfizer and Sangamo announced results of its gene therapy for severe hemophilia A
June 18, 2020: “Pfizer Inc. and Sangamo Therapeutics, Inc. announced updated follow-up data from the Phase 1/2 study of giroctocogene fitelparvovec (SB-525, or PF-07055480), an investigational gene therapy for patients with severe hemophilia A.

All five patients with severe hemophilia A who received the 3e13 vg/kg dose showed sustained factor VIII (FVIII) activity levels, with a median of 64.2% via chromogenic assay (patient-level geometric means after week 9 post-infusion).

No patients experienced bleeding events or required FVIII infusions. The factor VIII activity levels reflect measurements up to 61 weeks, the extent of follow-up for the longest-treated patient in the cohort.

These data are being presented today as a late-breaking oral abstract at the World Federation of Hemophilia 2020 World Congress, which is being held virtually from June 14 to June 19, 2020.

Giroctocogene fitelparvovec was generally well tolerated. As previously reported, one patient in the 3e13 vg/kg dose cohort had a treatment-related serious adverse event of hypotension (grade 3) and fever (grade 2), with symptoms of headache and tachycardia, which occurred six hours post-infusion with giroctocogene fitelparvovec, and which fully resolved within 24 hours.

No other treatment-related serious adverse events were reported. Among the five patients in the 3e13 vg/kg dose cohort, four received corticosteroids for liver enzyme (alanine aminotransferase, ALT) elevations.

Three patients had subsequent ALT elevations that responded to corticosteroids. All episodes of ALT elevations fully resolved with oral corticosteroids.

“We are excited that these data affirm previous findings from this Phase 1/2 study, and that all five patients have sustained levels of factor VIII activity with no bleeding events or use of factor replacement therapy.

We are encouraged by the potential of giroctocogene fitelparvovec to demonstrate longer-term durability, an important element for patients living with severe hemophilia A,” said Seng Cheng, Senior Vice President and Chief Scientific Officer of Pfizer’s Rare Disease Research Unit.

“The Phase 3 lead in study is ongoing, and we look forward to dosing patients with this investigational gene therapy in the pivotal Phase 3 trial later this year.”

“The current standard of care for severe hemophilia A requires regular infusions to replace missing Factor VIII.

Gene therapy, on the other hand, offers a new approach with the potential to provide a one-time treatment that would enable patients to produce the missing factor on their own,” said Bettina M. Cockroft, M.D., M.B.A., Chief Medical Officer of Sangamo.

“These follow-up data indicate that treatment with giroctocogene fitelparvovec resulted in sustained factor levels up to 14 months following treatment and suggests the potential of this investigational gene therapy to alleviate the treatment burden of current hemophilia disease management.”

The additional follow-up builds on data presented at the 61st Annual Meeting of the American Society of Hematology (ASH) in December 2019, which demonstrated that giroctocogene fitelparvovec was generally well tolerated and resulted in sustained FVIII levels up to 44 weeks, the extent of follow-up for the longest-treated patient in the 3e13 vg/kg dose cohort at that time.

The previously presented data included 11 patients treated across four ascending dose cohorts: 9e11 vg/kg (2 patients), 2e12 vg/kg (2 patients), 1e13 vg/kg (2 patients) and 3e13 vg/kg (5 patients).

Pfizer and Sangamo plan to present further follow-up data from the Alta study when all five patients in the 3e13 vg/kg dose cohort have been followed for at least one year.

Alta study

The Phase 1/2 Alta study is an open-label, dose-ranging, multicenter clinical trial designed to assess the safety and tolerability of giroctocogene fitelparvovec in patients with severe hemophilia A.

The mean age of the 11 patients assessed across four dose cohorts is 30 years (range 18-47 years). All 11 patients are male.

The U.S. Food and Drug Administration has granted Orphan Drug, Fast Track, and regenerative medicine advanced therapy (RMAT) designations to giroctocogene fitelparvovec, which also received Orphan Medicinal Product designation from the European Medicines Agency.

Giroctocogene fitelparvovec is being developed as part of a collaboration agreement for the global development and commercialization of gene therapies for hemophilia A between Sangamo and Pfizer.

Giroctocogene fitelparvovec

Giroctocogene fitelparvovec (SB-525 or PF-07055480), comprises a recombinant adeno-associated virus serotype 6 vector (AAV6) encoding the complementary deoxyribonucleic acid for B domain deleted human FVIII.

The giroctocogene fitelparvovec expression cassette was designed for optimal liver-specific expression of FVIII protein and supports production of high yields of the vector.

The giroctocogene fitelparvovec transcriptional cassette incorporates multi-factorial modifications to the liver-specific promoter module, FVIII transgene, synthetic polyadenylation signal and vector backbone sequence.

In late 2019, Sangamo transferred the manufacturing technology and the Investigational New Drug (IND) application to Pfizer. Pfizer is enrolling patients in the Phase 3 lead-in study (ClinicalTrials.gov Identifier: NCT03587116), the data from which is expected to provide a baseline for patients who are subsequently enrolled into the pivotal Phase 3 study (ClinicalTrials.gov Identifier: NCT04370054).

The primary endpoint of the Phase 3 study is annualized bleeding rate (ABR) over 12 months, and secondary endpoints include steady state FVIII activity levels, annualized infusion rate of exogenous FVIII activity, annualized FVIII consumption, ABR and total ABR of specific type by cause and by location, and change in joint health using Hemophilia Joint Health Score, over 12 months.”
https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-sangamo-announce-updated-phase-12-results

RINVOQ™Monotherapy Shows Improvement in Skin Clearance and Itch in First Phase 3 Study for Atopic Dermatitis

admin
-
0
RINVOQ™Monotherapy Shows Improvement in Skin Clearance and Itch in First Phase 3 Study for Atopic Dermatitis

June 18, 2020: “AbbVie announced upadacitinib (15 mg and 30 mg, once daily) monotherapy met the co-primary endpoints of at least a 75 percent improvement in the Eczema Area Severity Index (EASI 75) and a validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD) of clear or almost clear (0/1) at week 16 in adults and adolescents with moderate to severe atopic dermatitis who are candidates for systemic therapy.

Measure Up 1 is the first pivotal Phase 3 study to evaluate the efficacy and safety of RINVOQ for the treatment of moderate to severe atopic dermatitis.

In this study, patients receiving either 15 mg or 30 mg of upadacitinib monotherapy showed significant improvement in skin clearance.

Of patients receiving upadacitinib 15/30 mg, 70/80 percent achieved EASI 75 at week 16, respectively, versus 16 percent in the placebo group (p<0.001).

Of those treated with upadacitinib 15/30 mg, 48/62 percent of patients achieved vIGA-AD 0/1, respectively, versus 8 percent of patients receiving placebo (p<0.001).

“People with atopic dermatitis often struggle with relentless skin and itch symptoms, resulting in a significant unmet need,” said Michael Severino, M.D., vice chairman and president, AbbVie.

“We’re excited by these results, which show the potential of RINVOQ for individuals living with the burden of atopic dermatitis.”

For both doses, patients experienced an early reduction in itch, which was maintained through week 16.

Clinically meaningful reduction in itch was defined as improvement in Worst Pruritus Numerical Rating Scale (NRS)≥4, which was achieved by a significantly higher proportion of patients receiving upadacitinib 15/30 mg at week 16 compared to placebo (52/60 percent, respectively, versus 12 percent, p<0.001).

Clinically meaningful reductions in itch compared to placebo were observed as early as one day after the first dose (day 2) for patients receiving upadacitinib 30 mg (12 percent versus 4 percent, p<0.001) and two days after the first dose (day 3) for patients receiving upadacitinib 15 mg (16 percent versus 3 percent, p<0.001).

Measure Up 1 Results at Week 16
https://news.abbvie.com/news/press-releases/rinvoq-upadacitinib-monotherapy-shows-improvement-in-skin-clearance-and-itch-in-first-phase-3-study-for-atopic-dermatitis.htm

Atopic dermatitis is a common, chronic, relapsing, inflammatory skin disease that can manifest as a recurring cycle of itching and scratching leading to painful, cracked skin.

It affects up to an estimated 25 percent of adolescents and 10 percent of adults at some point in their lifetime.

Between 20 and 46 percent of adults with atopic dermatitis have moderate to severe disease.

The range of symptoms pose significant physical, psychological and economic burden on individuals impacted by the disease.

“Both adolescents and adults patients living with moderate to severe atopic dermatitis often suffer from an enormous burden of disease that can affect every aspect of their daily life,” said lead investigator Emma Guttman-Yassky, M.D., Ph.D., professor of dermatology and immunology, Icahn School of Medicine at Mount Sinai Medical Center. “It is encouraging to see the high proportion of patients achieving clear or almost clear skin with upadacitinib, and the meaningful and rapid reduction in itch with both doses.”

No new safety risks were observed compared to the safety profile observed in patients with rheumatoid arthritis and psoriatic arthritis receiving RINVOQ.

In Measure Up 1, serious adverse events occurred in 2.1 percent of patients receiving upadacitinib 15 mg, 2.8 percent of patients receiving upadacitinib 30 mg, and 2.8 percent of patients receiving placebo at week 16.

The most common treatment-emergent adverse events were acne, upper respiratory tract infection and nasopharyngitis.

Acne was observed with both doses of upadacitinib (6.8 percent of patients on 15 mg and 17.2 percent of patients on 30 mg) versus placebo (2.1 percent of patients) and was mild to moderate in most cases.

Eczema herpeticum was observed in patients receiving upadacitinib 30 mg (1.1 percent of patients) and placebo (1.4 percent of patients); it was not observed in patients receiving upadacitinib 15 mg.

Serious infections were reported infrequently (0.7 percent of patients receiving upadacitinib 15 mg or 30 mg; none were observed on placebo). No deaths, venous thromboembolic events (VTE) or major adverse cardiac events (MACE) were reported.

Full results from Measure Up 1 will be presented at a future medical meeting and published in a peer-reviewed publication. Use of RINVOQ in atopic dermatitis is not approved and its safety and efficacy have not been evaluated by regulatory authorities.

Related News: Data from RINVOQ&#Phase 3 Studies Presented at 2020 Annual European E-Congress of Rheumatolo
AbbVie Submits Regulatory Applications to FDA and EMA for RINVOQ™ for Psoriatic Arthritis
AbbVie Presents New Data at the European E-Congress of Rheumatology 2020

Measure Up 1 Study

Measure Up 1 is a Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled study designed to evaluate the safety and efficacy of upadacitinib in adult and adolescent (12 years or older) patients with moderate to severe atopic dermatitis who are candidates for systemic treatment.

Patients were randomized to upadacitinib 15 mg, upadacitinib 30 mg or placebo, followed by either upadacitinib 15 mg or upadacitinib 30 mg at week 16.

The co-primary endpoints were the percentage of patients achieving EASI 75 and a vIGA score of 0/1 after 16 weeks of treatment. Secondary endpoints included Improvement in Worst Pruritus NRS≥4 at week 16, EASI 90, percent change in Worst Pruritus NRS, percent change in EASI at week 16, as well as improvement in Worst Pruritus NRS≥4 at day 2 (one day after the first dose) for patients receiving upadacitinib 30 mg and improvement in Worst Pruritus NRS≥4 at day 3 (two days after the first dose) for patients receiving upadacitinib 15 mg.

The trial is ongoing, and the long-term extension period remains blinded to investigators and patients, to evaluate the long-term safety, tolerability and efficacy of the two once-daily doses (15 mg and 30 mg) of upadacitinib in patients who have completed the placebo-controlled period. More information on this trial can be found at www.clinicaltrials.gov (NCT03569293).

RINVOQ (upadacitinib)

Discovered and developed by AbbVie scientists, RINVOQ is an oral, once-daily, selective and reversible JAK inhibitor studied in several immune-mediated inflammatory diseases.

It was engineered to have greater inhibitory potency for JAK1 versus JAK2, JAK3 and TYK2.

In August 2019, RINVOQ received U.S. Food and Drug Administration approval for adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate.

In December 2019, RINVOQ also received approval by the European Commission for the treatment of adult patients with moderate to severe active rheumatoid arthritis who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs.

The approved dose for RINVOQ in rheumatoid arthritis is 15 mg. Phase 3 trials of RINVOQ in atopic dermatitis, rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, Crohn’s disease, ulcerative colitis and giant cell arteritis are ongoing.

Use of RINVOQ in atopic dermatitis is not approved and its safety and efficacy have not been evaluated by regulatory authorities.”
https://news.abbvie.com/news/press-releases/rinvoq-upadacitinib-monotherapy-shows-improvement-in-skin-clearance-and-itch-in-first-phase-3-study-for-atopic-dermatitis.htm

Novel Antibody-Drug Conjugate ABBV-3373 Shows Improvement for Rheumatoid Arthritis

admin
-
0
Novel Antibody-Drug Conjugate ABBV-3373 Shows Improvement for Rheumatoid Arthritis
 June 10, 2020: “AbbVie, a research-based global biopharmaceutical company announced new data from a Phase 2a study of ABBV-3373, an investigational anti-tumor necrosis factor (TNF) Glucocorticoid Receptor Modulator (GRM) steroid antibody drug conjugate (ADC), in adult patients with moderate to severe rheumatoid arthritis.

The primary endpoint was the change in Disease Activity Score 28 C-Reactive Protein (DAS28-CRP) from baseline to week 12 and two statistical comparisons were pre-specified.

The first compared ABBV-3373 and mean outcome from historical adalimumab data.

 The second compared ABBV-3373 and combined in-trial and historical adalimumab data.

Results of the first comparison show a greater difference in the primary endpoint change in DAS28-CRP from baseline to week 12 for ABBV-3373 (-2.65) as compared to a pre-specified historical adalimumab mean (-2.13) (p=0.022).

 Results of the second comparison, based on a Bayesian analysis, predicted with a 90 percent probability that ABBV-3373 was associated with a greater improvement on DAS28-CRP from baseline to week 12 than adalimumab based on in-trial data combined with historical data.

 Additionally, evaluations of serum cortisol levels over 12 weeks indicate that ABBV-3373 showed no systemic glucocorticoid effects.

“This proof of concept study demonstrates clinical activity of the TNF-ADC platform and its potential to advance the standard of care for patients with rheumatoid arthritis,” said Michael Severino, M.D., vice chairman and president, AbbVie. “Based on these results we will advance the development of the TNF-ADC platform in rheumatoid arthritis and begin clinical studies in other immune-mediated diseases.”

These are the first results to be reported for the novel ADC in rheumatoid arthritis. ABBV-3373 is an investigational medicine that is not approved by regulatory authorities and is being studied for the treatment of rheumatoid arthritis and other immune-mediated diseases.

Full results from this study will be presented at an upcoming medical meeting and/or published in a peer-reviewed publication.  

In the 31 rheumatoid arthritis patients on ABBV-3373 and 17 rheumatoid arthritis patients on adalimumab, in the trial, the safety profile of ABBV-3373 was generally similar to adalimumab.

 The overall adverse events (AE) rate of ABBV-3373 was lower than adalimumab (35 percent [n=11] vs. 71 percent [n=12], respectively).

The AEs occurring in ≥5 percent of patients were urinary tract infections, with two events in each treatment group, and headache, with two events in the ABBV-3373 group and one event in the adalimumab group.

Six percent (n=1) of subjects treated with adalimumab and three percent (n=1) of subjects treated with ABBV-3373 discontinued treatment due to an AE.

Through week 12, serious adverse events (SAEs) occurred in four patients in the ABBV-3373 group (13 percent, [n=4]), compared to none in the adalimumab group (0 percent, [n=0]).

In the ABBV-3373 group, two SAEs were deemed unrelated to study drug (pneumonia and upper respiratory tract disease).

One SAE was non-cardiac chest pain and one SAE was reported as anaphylactic shock; this subject fully recovered and no further events of hypersensitivity were reported after drug administration time was extended for subsequently dosed subjects.

ABBV-3373

Being developed by AbbVie, ABBV-3373 is an investigational ADC comprised of a novel glucocorticoid receptor modulator (GRM) linked to adalimumab, and aims at modulating TNF-mediated inflammatory pathways by delivering a glucocorticoid payload directly into activated immune cells expressing membrane bound TNF.

This ADC was designed to potentially allow precise targeting of activated immune cells while significantly dampening inflammation and minimizing the systemic side-effects associated with glucocorticoids.

ABBV-3373 is an investigational medicine that is not approved by regulatory authorities and is being studied for the treatment of rheumatoid arthritis and other immune-mediated diseases.

M16-560 Study

The M16-560 study is a Phase 2a, multicenter, randomized, double-blind, double-dummy, active-controlled study designed to evaluate the safety, tolerability, pharmacokinetics and efficacy of ABBV-3373 in adult patients with moderate to severe rheumatoid arthritis with an inadequate response to MTX.

Patients were randomized in a 2:1 ratio to ABBV-3373 (n=31) at 100 mg, every other week (EOW) or adalimumab (n=17) at 80 mg, EOW for 12 weeks.

Bayesian statistical methods incorporating historical data were used to achieve adequate statistical power in this proof of concept study, which was accomplished through pre-specified supplementation of adalimumab in-trial data with historical adalimumab data for comparison with ABBV-3373 for the primary endpoint analyses.

The historical data were obtained from three historical adalimumab trials of similar settings. The primary endpoint was the change in DAS28-CRP from baseline to week 12 and two statistical comparisons were pre-specified.

The first compared ABBV-3373 and mean outcome from historical adalimumab data with the success criteria of two-sided p-value ≤0.1.

The second compared ABBV-3373 and combined in-trial and historical adalimumab data (success criterion: probability of >95 percent).

Important Safety Information about HUMIRA™ (adalimumab)

HUMIRA U.S. Use and Important Safety Information

HUMIRA is a prescription medicine used to reduce the signs and symptoms of moderate to severe rheumatoid arthritis in adults. HUMIRA can be used alone, with methotrexate, or with certain other medicines.

HUMIRA may prevent further damage to bones and joints and may help the ability to perform daily activities.

HUMIRA is a TNF blocker medicine that affects the immune system and can lower the body’s ability to fight infections. Serious infections have happened in people taking HUMIRA.

These serious infections include tuberculosis (TB) and infections caused by viruses, fungi, or bacteria that have spread throughout the body.

Some people have died from these infections. People should be tested for TB before HUMIRA use and monitored for signs and symptoms of TB during therapy, even if their TB test was negative. People at risk of TB may be treated with medicine for TB.

Treatment with HUMIRA should not be started in a person with an active infection, unless approved by a doctor.

HUMIRA should be stopped if a person develops a serious infection. People should tell their doctor if they live in or have been to a region where certain fungal infections are common, as these infections may happen or become more severe if people use HUMIRA.

People should tell their doctor if they have had TB or hepatitis B, are prone to infections, or have symptoms such as fever, fatigue, cough, or sores.

For people taking TNF blockers, including HUMIRA, the chance of getting lymphoma or other cancers may increase. Some people have developed a rare type of cancer called hepatosplenic T-cell lymphoma.

This type of cancer often results in death. If using TNF blockers, including HUMIRA, the chance of getting two types of skin cancer (basal cell and squamous cell) may increase.

These types are generally not life-threatening if treated.

Other possible serious side effects with HUMIRA include hepatitis B infection in carriers of the virus; allergic reactions; nervous system problems; blood problems; certain immune reactions, including a lupus-like syndrome; liver problems; and new or worsening heart failure or psoriasis.

The use of HUMIRA with anakinra or abatacept is not recommended. People using HUMIRA should not receive live vaccines. Children should be brought up to date on all vaccines before starting HUMIRA.

Common side effects of HUMIRA include injection site reactions (redness, rash, swelling, itching, or bruising), upper respiratory infections (including sinus infections), headaches, rash, and nausea.

HUMIRA is given by injection under the skin.

The benefits and risks of HUMIRA should be carefully considered before starting therapy.”
https://news.abbvie.com/news/press-releases/novel-antibody-drug-conjugate-abbv-3373-shows-improvement-in-disease-activity-in-phase-2a-study-patients-with-rheumatoid-arthritis.htm

AbbVie and Genmab Announce Broad Oncology Collaboration

admin
-
0
AbbVie and Genmab Announce Broad Oncology Collaboration

 June 10, 2020: “AbbVie and Genmab A/S announced that AbbVie and Genmab have signed a broad collaboration agreement to jointly develop and commercialize three of Genmab’s early-stage investigational bispecific antibody product candidates and enter into a discovery research collaboration for future differentiated antibody therapeutics for cancer.

The companies will partner to develop Genmab’s next-generation bispecific antibody programs, epcoritamab (DuoBody®-CD3xCD20), DuoHexaBody®-CD37 and DuoBody-CD3x5T4. 

The collaboration combines Genmab’s world-class discovery and development engine and next-generation bispecific antibody therapeutic candidates with AbbVie’s deep clinical expertise, innovative antibody-drug conjugate (ADC) platform and global commercial leadership in hematological cancers.

The discovery research collaboration will combine proprietary antibodies from both companies along with Genmab’s DuoBody technology and AbbVie’s payload and ADC technology to select and develop up to four additional differentiated next-generation antibody-based product candidates, potentially across both solid tumors and hematological malignancies. Genmab’s DuoBody-CD3 technology engages and directs cytotoxic T cells selectively to tumors to elicit an immune response towards malignant tumor cells.

AbbVie’s ADC technology allows the delivery of a therapeutic toxin directly to cancer cells while sparing normal, healthy cells, providing for a more targeted, less toxic treatment approach.

“This transformative collaboration will allow us to accelerate, broaden and maximize the development of some of our promising early-stage bispecific antibodies, including epcoritamab, with the ultimate goal of bringing these potential therapies much faster to cancer patients,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

“Today’s announcement marks the beginning of a new journey for Genmab that combines our world-class knowledge in antibody biology and deep expertise in truly innovative next-generation antibody technology platforms, with AbbVie’s R&D prowess and their leadership position in hematological cancers.”

“Epcoritamab is a strong fit for our robust hematological oncology franchise”, said Michael Severino, M.D., Vice Chairman and President, AbbVie. “By combining the strengths of our two organizations, we can advance the treatment landscape for patients battling cancer.”

Collaboration Details
This collaboration will provide for the joint development and commercialization of the three bispecific antibody therapeutic candidates. For epcoritamab, the companies will share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization.

Genmab will book net sales in the U.S. and Japan and receive tiered royalties on remaining global sales.

For DuoHexaBody-CD37, DuoBody-CD3x5T4 and any product candidates developed as a result of the companies’ discovery research collaboration, Genmab and AbbVie will share responsibilities for global development and commercialization in the U.S. and Japan.

Genmab retains the right to co-commercialize these products, along with AbbVie, outside of the U.S. and Japan.

For the discovery research partnership, Genmab will conduct Phase 1 studies for these programs. AbbVie retains the right to opt-in to program development.

Financial Terms
Under the terms of the agreement, AbbVie will pay Genmab USD 750 million in upfront payment with the potential for Genmab to receive up to USD 3.15 billion in additional development, regulatory and sales milestone payments for all programs as well as tiered royalties between 22% and 26% on net sales for epcoritamab outside the U.S. and Japan.

Except for these royalty-bearing sales, the parties share in pre-tax profits from the sale of products on a 50:50 basis. Included in these potential milestones are up to USD 1.15 billion in payments related to clinical development and commercial success across the three existing bispecific antibody programs.

In addition, if all four next-generation antibody product candidates developed as a result of the discovery research collaboration are successful, Genmab is eligible to receive up to USD 2.0 billion in option exercise and success-based milestone payments.

Epcoritamab (DuoBody-CD3xCD20)
Epcoritamab (DuoBody-CD3xCD20) is a bispecific antibody created using Genmab’s proprietary DuoBody technology.

Epcoritamab is designed to target CD3, which is expressed on T cells and is part of the T cell receptor signaling complex, and CD20, a clinically well validated therapeutic target.

CD20 is expressed on a majority of B cell malignancies, including chronic lymphocytic leukemia (CLL), diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL) and mantle cell lymphoma (MCL).

In a number of laboratory models, epcoritamab has shown highly effective killing of CD20+ tumors and induced potent tumor cell lysis across a panel of B cell tumor lines. Epcoritamab is currently evaluated in a Phase 1/2 study for multiple hematological B cell malignancies.

Complete dose escalation data for epcoritamab was presented at the American Society of Clinical Oncology 2020 (ASCO20) Virtual Scientific Program. 

The data and preliminary activity from the Phase 1/2 study of subcutaneous epcoritamab in patients with relapsed / refractory B-cell non-Hodgkin lymphoma (B-NHL) are highly encouraging showing substantial single-agent activity for epcoritamab with a manageable safety profile.

In the study, epcoritamab induced rapid and deep responses in heavily pretreated patients with B-NHL across different subtypes and no dose-limiting toxicities were observed.”

https://news.abbvie.com/news/press-releases/abbvie-and-genmab-announce-broad-oncology-collaboration.htm

Kawasaki-like syndrome linked to COVID-19 in children is a new condition

admin
-
0
Kawasaki-like syndrome linked to COVID-19 in children is a new condition
June 08, 2020: “A study on children suffering from severe inflammatory symptoms shows the condition is new and distinct from Kawasaki disease.

A study led by researchers at Imperial College Academic Health Science Centre (AHSC), a joint initiative between Imperial College London and three NHS hospital trusts, has now identified the key symptoms and clinical markers of this new syndrome, which should advance its diagnosis and treatment.

The researchers studied the condition – now called Paediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2 (PIMS-TS) – in 58 children admitted to eight hospitals across England.

They found that on average it appears to affect older children than Kawasaki disease (nine years versus four years old, respectively), and that it tends to present with abdominal pains and diarrhoea alongside the common features such as fever.

The research also suggests that Black and Asian patients are more susceptible.

Also of crucial importance, blood tests from these patients show different results to those with Kawasaki disease, with more markers of inflammation and cardiac enzymes, suggesting that the heart is under greater strain in those with PIMS-TS.

Kawasaki disease restricts the growth of the coronary artery thus reducing the flow of blood to the heart.

Doctors use immune therapy to address this issue and have also been using this treatment strategy in patients with PIMS-TS, though the researchers note that given the clear differences between the two conditions this needs further investigation.

The research team is unable to definitely conclude at this time that PIMS-TS is caused by COVID-19, but given that 45 of the 58 children been infected with the virus, it is believed likely.

Also, most of the children who exhibited signs of past infection had antibodies for novel coronavirus, which suggests that PIMS-TS develops after infection, possibly because of immune system over-drive.

“An important next step will be to review this data in the context of other studies being published from around the world.

This will help inform management guidelines and to further refine the case definition,” noted Dr Alasdair Bamford, consultant and specialty lead in paediatric infectious diseases at Great Ormond Street Hospital.

The research paper Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2, by Elizabeth Whittaker et al was published in the Journal of the American Medical Association.”
https://www.imperial.ac.uk/news/198077/kawasaki-like-syndrome-linked-covid-19-children-condition/

Soleno Therapeutic’s drug misses a key goal in Prader-Willi trial

admin
-
0
Soleno Therapeutic’s drug misses a key goal in Prader-Willi trial
June 08, 2020: “Soleno Therapeutics announced top-line results from the Company’s Phase III trial, DESTINY PWS (C601), evaluating once-daily Diazoxide Choline Controlled-Release (DCCR) tablets for patients with Prader-Willi Syndrome (PWS).

DESTINY PWS/C601

The study did not meet its primary endpoint of change from baseline in hyperphagia. The change was measured by the total score of a Hyperphagia Questionnaire for Clinical Trials (HQ-CT, 0‑36).

An improvement in HQ-CT is represented by a decrease in the score.

The mean (SE) change from baseline for DCCR was -5.94 (0.879) and for placebo was -4.27 (1.145). The least squares mean difference in HQ-CT score of DCCR compared with placebo was -1.67 (1.294); 95% confidence interval (-4.24, 0.89); p=0.1983.

Significant changes were observed in two of three key secondary endpoints from baseline to week 13 in subjects receiving DCCR as compared to placebo:

  • Improvement in Clinical Global Impression of Improvement (CGI-I) score as assessed by the investigator (p=0.029)
  • Reduction of body fat mass measured by DXA scan (p=0.025)

In a prespecified subgroup of subjects (n=61) with more severe hyperphagia, as identified by a dichotomized median baseline HQ-CT score of >22, the mean (SE) change from baseline for DCCR (n=42) was -9.67 (1.429) and for placebo (n=19) was -4.26 (1.896).

The least squares mean difference in HQ-CT score of DCCR compared with placebo was -5.41 (2.093); 95% confidence interval (-9.60, -1.22); p=0.0124.

In addition to the reduction in total body fat mass, other body composition changes in DCCR compared to placebo included significant decreases in trunk fat mass (p = 0.047), and improvement in lean body mass to fat mass ratio (p=0.001).

Fat mass changes were most pronounced in subjects in the highest weight band (n=18, 100-135 kg); p=0.024.

“Hyperphagia, the predominant symptom of PWS, is an unrelenting hunger that can cause life-threatening co-morbidities, including obesity, and is a condition for which no treatments are available,” said Jennifer L. Miller, M.D., Professor in the Division of Pediatric Endocrinology at the University of Florida and a Principal Investigator in the Soleno study.

“PWS also leads to significant quality-of-life challenges for patients and families.

These data show that DCCR therapy results in meaningful improvements in hyperphagia in severe patients, as well as various other positive impacts in behaviours and body composition, and if approved, could offer a safe and effective treatment to PWS patients struggling to manage their symptoms.

My experience with DCCR in the largest cohort of patients in this study is consistent with the overall effects seen in DESTINY PWS.”

DESTINY PWS is a multi-center, randomized, double-blind, placebo-controlled study of once‑daily oral administration DCCR in 127 PWS patients at 29 sites in the U.S. and UK.

The objective of the study was to assess the safety and efficacy of DCCR in subjects ages four years and older, with genetically-confirmed PWS.

Patients who completed the double-blind study were eligible to enroll in study C602. For further information about DESTINY PWS (NCT03440814) and Study C602 (NCT03714373), please visit: www.clinicaltrials.gov.

Study C602 – Long-term Safety Extension Study – Interim Data

A total of 115 subjects were enrolled into C602, an ongoing open-label, safety extension study of DCCR in PWS patients completing C601, and >90% of them are continuing to be treated at this time.

An interim analysis of subjects (n=63) who have completed three months of treatment on C602 shows continuing improvements in hyperphagia.

DCCR subjects from C601 (n= 38) at six months of treatment demonstrated a reduction in hyperphagia score of -11.7 (-48%) and placebo subjects from C601 who switched to DCCR showed a similar change following three months of treatment in C602.

Behaviors related to PWS are measured using a PWS Profile Questionnaire (PWS-P), which consists of caregiver responses to questions in six domains: aggressive behaviors, anxiety, rigidity-irritability, compulsivity, depression and disordered thinking.

Improvements in most domains were seen in C601 with DCCR treatment. In subjects from C601 treated with DCCR, each domain showed further improvement in C602.

Placebo subjects from C601 who switched to DCCR showed a similar change following three months of treatment in C602.

PWS Outcomes Study – Interim Data

An interim analysis of a subset of subjects in the PWS outcomes study was conducted consisting of data from interviews at the end of C601 for caregivers of 27 patients (17 DCCR and 10 placebo).

The interviews evaluated individual patient experiences with DCCR and placebo using three domains: food-related improvements, non-food-related improvements and daily life improvements.

In each of these domains, approximately 48% participants on DCCR reported at least some positive improvement, with 18-24% reporting a major improvement in the PWS patient. In the placebo group, a single participant (10%) reported a minor improvement in their PWS patient, and none reported a major difference.

“While we are disappointed to have not achieved statistical significance on the study’s primary endpoint, we are excited by the results observed in those subjects with severe hyperphagia, as well as the changes in body composition and behavioral endpoints,” said Anish Bhatnagar, M.D., Chief Executive Officer of Soleno Therapeutics.

“Based on these data, we will continue treatment of patients on C602. We are continuing to evaluate the data from C601 and C602 and plan to meet with regulatory authorities to determine next steps.

On behalf of the Soleno team, I would like to thank the patients, families and investigators involved in this study, as well as the Foundation for Prader-Willi Research and Prader-Willi Syndrome Association USA and UK, for their support of the DCCR Phase III development program.” 

DCCR Safety
The safety profile of DCCR in C601 was generally consistent with the known profile of diazoxide and prior experience with DCCR.

Treatment emergent adverse events (TEAEs) were reported in 70 (83.3%) DCCR subjects and 31 (73.8%) placebo subjects.

TEAEs that were reported more frequently in the DCCR group vs. placebo and occurred in at least 5% of DCCR subjects were hypertrichosis (35.7% vs. 14.3%), peripheral edema (20.2% vs 9.5%), blood glucose increase (6% vs. 4.8%), hyperglycemia (11.9% vs. 0%) and pyrexia (6% vs. 0%).

Most events were Grade 1 in severity, including all events of hypertrichosis (other than one Grade 2 in the placebo group). No Grade 4 or higher events were reported in this study.

Five subjects discontinued from the study early due to adverse events, four in the DCCR group and one in the placebo group. Six subjects had serious TEAEs in the DCCR group and none in the placebo group.

There were no serious unexpected adverse events (SUSARs) related to DCCR.

Study visits in C601 and C602 conducted after approximately mid-March were impacted by COVID-19. Certain evaluations could have been conducted in a different manner and evaluations, such as DXA, were not conducted in most cases during this period. Additional analyses will evaluate the impact of these changes.  

DCCR has orphan designation for the treatment of PWS in the U.S. and EU and Fast Track designation from the U.S. Food and Drug Administration.”
http://investors.soleno.life/news-releases/news-release-details/soleno-therapeutics-announces-top-line-results-phase-iii-trial

Coronavirus (COVID-19) Update: Daily Roundup June 9, 2020

admin
-
0
Coronavirus (COVID-19) Update: Daily Roundup June 9, 2020

June 09, 2020: “The U.S. Food and Drug Administration announced the following actions taken in its ongoing response effort to the COVID-19 pandemic:

  • On June 8, 2020, the FDA approved an abbreviated new drug application for succinylcholine chloride injection USP 200 mg/10 mL, which is indicated in addition to general anaesthesia, to facilitate tracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation.

    Side effects of succinylcholine chloride injection include anaphylaxis, hyperkalemia, and malignant hyperthermia.

    The FDA recognizes the increased demand for certain products during the COVID-19 public health emergency, and we remain deeply committed to facilitating access to safe and effective medical products to help address critical needs of the American public.
  • The FDA issued a warning letter to one company for selling a fraudulent COVID-19 product, as part of the agency’s effort to protect consumers.

    The seller that received FDA’s warning, organic-beauty-recipes.com, participates in the Amazon Associates program.

    As an Amazon associate, the company earns commissions on its website for promoting the sale on Amazon of certain products. 

    One essential-oil product promoted by the site is accompanied by misleading claims that this product can mitigate, prevent, treat, diagnose, or cure COVID-19 in people.

    FDA requested the company immediately stop promoting and participating in the sale of the fraudulent COVID-19 product.

    There are currently no FDA-approved products to prevent or treat COVID-19. Consumers concerned about COVID-19 should consult with their health care provider.
  • Testing updates:
    • To date, the FDA has authorized 128 tests under EUAs, which include 108 molecular tests, 19 antibody tests, and 1 antigen test.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices.

The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.”
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-daily-roundup-june-9-2020

Oxford Biomedica and VMIC Announces Collaboration

admin
-
0
Oxford Biomedica and VMIC Announces Collaboration
June 08, 2020: “Oxford Biomedica plc, a leading gene and cell therapy group, announced that it has signed a Collaboration Agreement with the Vaccines Manufacturing and Innovation Centre (VMIC), a not-for-profit organisation established to provide the UK’s first strategic vaccine development and advanced manufacturing capability.

This five year Agreement will involve the organisations working collaboratively to enable the manufacture of viral vector based vaccines, contributing towards a rapid increase in UK domestic capacity for this specialised field of vaccine manufacturing.

Both Oxford Biomedica and VMIC are original members of the Oxford University manufacturing consortium focussed on scaling-up the GMP manufacture of the adenovirus vector based COVID-19 vaccine candidate, AZD1222 (previously known as ChAdOx1 nCoV-19), which has entered clinical trials at multiple sites in the UK.

AstraZeneca has now taken over global responsibility for the manufacturing, development and distribution for AZD1222 with an initial clinical and commercial supply agreement for multiple batches signed between AstraZeneca and Oxford Biomedica on the 28 May.

As part of the Collaboration Agreement, VMIC will provide manufacturing equipment for Oxford Biomedica to rapidly equip two new GMP manufacturing suites within Oxford Biomedica’s new 7,800 m2 commercial manufacturing centre, Oxbox, located in Oxford, UK.

This will provide significant additional manufacturing capacity and enable further scale up for AZD1222 from the summer of 2020 as needed to help supply UK and European vaccine demand.

These suites could also potentially be utilised for other viral vector vaccine candidates. As part of the Agreement, Oxford Biomedica will provide training and technical assistance to VMIC staff to accelerate the operational readiness and GMP manufacturing capabilities for viral vector vaccine candidates at VMIC’s new manufacturing site located at the Harwell Science and Innovation Campus.

The VMIC facility is due to open in mid-2021, a year ahead of schedule.

The Agreement also provides a framework for a longer-term partnership between Oxford Biomedica and VMIC, whereby Oxford Biomedica could rapidly provide its commercial scale manufacturing capacity to supply other novel viral vector vaccine candidates for the UK population, when needed.

John Dawson, Chief Executive Officer of Oxford Biomedica, said: “
Since we became involved in addressing the urgent need for UK manufacturing capacity for AstraZeneca’s COVID-19 vaccine candidate AZD1222, we have strived to support VMIC’s broader goal of accelerating and supporting UK manufacturing capacity and capabilities for vaccines more generally.

This highly collaborative partnership allows for a rapid deployment capability to be established, and also accelerates fit out and utilisation of another two GMP manufacturing suites within our new commercial manufacturing facility, Oxbox.”

Matthew Duchars, Chief Executive Officer of Vaccines Manufacturing Innovation Centre, said:
“This collaboration with Oxford Biomedica means that together we can significantly increase the UK’s capacity to manufacture viral vectors vaccines as part of a national effort in response to COVID-19.

This marks a major milestone for VMIC in setting up collaborative partnerships with industry – this is the first collaboration agreement outside of our founding partners under VMIC’s longer term objective of boosting the UK’s vaccines manufacturing capability.”

Kate Bingham, Chair of the UK Vaccine Taskforce, said: “
The Government is backing the Vaccines Manufacturing and Innovation Centre as a crucial part of securing long-term vaccine manufacturing capability in the UK. Viral vector Covid-19 vaccine candidates are showing significant promise. “

This new partnership between VMIC and Oxford Biomedica marks a major milestone in increasing the UK manufacturing capacity of viral vector vaccines and will specifically help ensure that we have the right skills in place to manufacture a vaccine as soon as one is available.”
https://www.oxfordbiomedica.co.uk/news-media/press-release/oxford-biomedica-signs-five-year-collaboration-agreement-vaccines

Coronavirus (COVID-19) Update: Daily Roundup June 8, 2020

admin
-
0
Coronavirus (COVID-19) Update: Daily Roundup June 8, 2020
June 08, 2020: “The U.S. Food and Drug Administration announced the following actions taken in its ongoing response effort to the COVID-19 pandemic:
  • On June 6, 2020, in response to public health and safety concerns about the appropriateness of decontaminating certain respirators, the FDA issued certain Emergency Use Authorizations (EUAs) to revise which respirators the decontamination systems are authorized to decontaminate.

    The FDA also reissued two EUAs covering imported respirators by tightening other criteria in the Non-NIOSH-Approved Disposable Filtering Facepiece Respirators Manufactured in China as well as in the Imported, Non-NIOSH-Approved Disposable Filtering Facepiece Respirators.
  • The FDA issued a guidance, titled “Temporary Policy on Prescription Drug Marketing Act Requirements for Distribution of Drug Samples During the COVID-19 Public Health Emergency.”

    The guidance addresses questions FDA has received concerning prescription drug sample distribution under the Prescription Drug Marketing Act of 1987 (PDMA) during the COVID-19 public health emergency.

    The guidance explains that, on a temporary basis, the FDA does not intend to object to the delivery of prescription drug samples to patients’ homes if requested by their licensed health care professional, and the guidance describes the agency’s current policy regarding the signature required at time of delivery of drug samples, to promote public health.
  • On June 8, 2020, the FDA added the BioMedInnovations SuppleVent Ventilator to the list of ventilators authorized under the March 24, 2020, EUA for certain ventilators, ventilator tubing connectors, and ventilator accessories.

    This ventilator provides continuous ventilatory support for adult patients who require mechanical ventilation.

    The ventilator is intended for institutional use by qualified, trained personnel under the direction of a doctor.

    Institutional use includes use in an intensive care unit or other hospital environments such as during intra-hospital transport and in temporary hospital facilities.

    Lawrence Livermore National Laboratory collaborated in the design of the ventilator.
  • FDA published two new web pages to help the public access information: (1) Innovation to Respond to COVID-19 provides an overview of FDA’s innovative approaches to respond to COVID-19 as quickly and safely as possible and (2) Educational Resources provides links to FDA-produced COVID-19-related resources that help explain FDA’s work.

    Related News: https://lifepronow.com/blog/2020/06/05/coronavirus-covid-19-update-daily-roundup-june-4-2020/
  • Testing updates:
    • To date, the FDA has authorized 125 tests under EUAs, which include 107 molecular tests, 17 antibody tests, and 1 antigen test.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices.

The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.”
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-daily-roundup-june-8-2020

Sanofi to present Phase 3 results of avalglucosidase alfa in patients with late-onset Pompe disease

admin
-
0
Sanofi to present Phase 3 results of avalglucosidase alfa in patients with late-onset Pompe disease
June 8, 2020: “Sanofi will host a virtual scientific session to present data from the Phase 3 COMET trial of investigational enzyme replacement therapy (ERT) avalglucosidase alfa in patients with late-onset Pompe disease (LOPD).  

The session, open to healthcare professionals and members of the media, will include a data presentation by Jordi Diaz-Manera, M.D., Ph.D., Professor of Neuromuscular Disorders, Translational Medicine and Genetics at the John Walton Muscular Dystrophy Research Center, Newcastle University, UK, and Professor of Neuromuscular Diseases, Translational Medicine and Genetics in the Neuromuscular Diseases Unit, Neurology department of Hospital de la Santa Creu, Barcelona, Spain.

The presentation will be followed by a Q&A session moderated by Alaa Hamed, M.D., MPH, MBA, Global Head of Medical Affairs, Rare Diseases at Sanofi.
             

The scientific session, endorsed by the COMET trial author group, is being scheduled as a result of the postponement of the July 2020 International Congress on Neuromuscular Diseases (ICNMD) due to the COVID-19 pandemic.

Data from the Phase 3 COMET trial would have been presented at the July 2020 ICNMD. Pre-registration is required for the June 16, 2020 scientific session.

The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation status to avalglucosidase alfa for the treatment of patients with a confirmed diagnosis of Pompe disease.

Breakthrough Therapy designation serves to expedite the development and review of drugs that target serious or life-threatening conditions.

Drugs qualifying for this designation must show preliminary clinical evidence of a substantial improvement on a clinically significant endpoint over available therapies, or over placebo if there is no available therapy.

Pompe disease

Pompe disease is caused by a genetic deficiency or dysfunction of the lysosomal enzyme acid alpha-glucosidase (GAA), resulting in build-up of glycogen in muscles, including the proximal muscles and the diaphragm, and eventually causing progressive and irreversible muscle damage.

This rare disease affects an estimated 50,000 people worldwide and can manifest at any age from infancy to late adulthood.

Pompe disease is often classified as late-onset Pompe disease (LOPD) or infantile-onset Pompe disease (IOPD).

Patients with LOPD typically present any time after the first year of life to late adulthood. The hallmark symptoms of LOPD are impaired respiratory function and skeletal muscle weakness, which often leads to impaired mobility.

Patients often require wheelchairs to assist with mobility and may require mechanical ventilation to help with breathing.

Respiratory failure is the most common cause of death in patients with Pompe disease.

Pompe disease is classified as IOPD when symptoms begin prior to one year of age. In addition to skeletal muscle weakness, heart function is also commonly impacted. 

Avalglucosidase alfa

The goal of ERT for Pompe disease is to deliver enzyme into the lysosomes within muscle cells to replace the missing or deficient GAA that is needed to prevent build-up of glycogen in the muscles.

Avalglucosidase alfa is an investigational ERT for Pompe disease designed to improve the delivery of enzyme to the cells in the muscles, most notably into skeletal muscle.

With approximately 15 moles of mannose-6-phosphate (M6P) per mole of GAA, avalglucosidase alfa aims to help improve cellular enzyme uptake and enhance glycogen clearance in target tissues.iii

The FDA granted Fast Track designation to avalglucosidase alfa for the treatment of patients with Pompe disease.

Avalglucosidase alfa has not been approved by the U.S. FDA or any other regulatory agency worldwide for the uses under investigation.”
https://www.sanofi.com/en/media-room/press-releases/2020/2020-06-03-18-00-00

New Pilot Program to Help Stop Illegal Availability of Unapproved Opioids Online

admin
-
0
New Pilot Program to Help Stop Illegal Availability of Unapproved Opioids Online
June 08, 2020: “The U.S. Food and Drug Administration and the National Telecommunications and Information Administration (NTIA) are launching a 120-day pilot to help reduce the availability of unapproved opioids illegally offered for sale online.

Under the pilot, the FDA will notify internet registries that are participating in the pilot – Neustar, Verisign and Public Interest Registry – when the agency sends a warning letter to a website operator and the website operator does not respond adequately within the required timeframe.

The internet registries will review the FDA’s notifications and assess whether to take further voluntary action, including possible domain name suspensions or blocks.

The NTIA, a branch of the U.S. Department of Commerce, responsible for telecommunications and information policy issues, will work with the internet registries involved in the pilot, and partner with the FDA to assess its impact.

“Cooperation between the Department of Health and Human Services and the Department of Commerce, with the addition of the pilot program, will help stop the online sale of illicit opioids and combat our country’s deadly addiction crisis,” said HHS Secretary Alex Azar.

“Stopping abuse of illegal opioids, including those sold online, has been one of President Trump’s top health priorities.

The men and women of FDA have worked tirelessly over the years with the private sector and federal partners, like NTIA, to fight illegal online opioid sales.”

“The trusted notifier pilot program is another new policy tool in President Trump’s fight to end the opioid crisis,” said Secretary of Commerce Wilbur Ross. “The Commerce Department is eager to work with our partners at HHS, FDA, and the domain name registries to remove a major channel for the sale of illicit opioids, which will help save many American lives.”

At the end of the pilot, the agencies will analyze its effectiveness as a potential solution to dealing with the illegal sale of unapproved opioids online.

The FDA remains committed to addressing the national opioid crisis on all fronts, with a continued focus on decreasing exposure to opioids and preventing new addiction; supporting the treatment of those with opioid use disorder; fostering the development of novel pain treatment therapies; and taking action against those who contribute to the illegal sale and importation of unapproved opioids.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.”
https://www.fda.gov/news-events/press-announcements/federal-government-announces-new-pilot-program-help-stop-illegal-availability-unapproved-opioids

FibroGen Announces First Patient Enrolled in Pamrevlumab Clinical Trial in Patients Hospitalized in Italy with Severe COVID-19

admin
-
0
FibroGen Announces First Patient Enrolled in Pamrevlumab Clinical Trial in Patients Hospitalized in Italy with Severe COVID-19

June 08, 2020, FibroGen, Inc. (NASDAQ: FGEN) today announced the initiation of an open-label, randomized, parallel-arm study investigating the efficacy and safety of pamrevlumab versus standard of care in patients with severe coronavirus 2019 (COVID-19) infection.

The trial is being conducted by Professor Luca Richeldi, M.D., Ph.D., Head of the Division of Pulmonary Medicine at Fondazione Policlinico Universitario A. Gemelli IRCCS, and Professor of Respiratory Medicine at Catholic University of the Sacred Heart in Rome, Italy.

BOREA is a Phase 2/3 investigator-initiated clinical trial investigating the efficacy and safety of pamrevlumab in approximately 68 patients hospitalized with COVID-19. The primary objective of this study is to assess the effect of pamrevlumab on blood oxygenation in patients with COVID-19 infection. Patients will be randomized to treatment with pamrevlumab or standard of care in a 1:1 ratio.

Based on the investigator’s decision, a subgroup of patients may continue treatment for up to 12 weeks.

“Recent data indicate the presence of interstitial pneumonia in the majority of hospitalized patients infected with COVID-19. The interstitial pneumonia is usually bilateral and leads to decreased blood oxygen levels, respiratory failure, intubation, and, ultimately, death in a significant proportion of patients who require mechanical ventilation,” said Elias Kouchakji, M.D., Senior Vice President, Clinical Development, Drug Safety, and Pharmacovigilance, FibroGen. “Connective tissue growth factor (CTGF) may promote vascular leakage and lead to pulmonary edema.

Administration of pamrevlumab, an anti-CTGF monoclonal antibody, may reverse this edema, and thus improve oxygenation in patients with COVID-19-induced pneumonia.”

Pamrevlumab is a first-in-class antibody developed by FibroGen to inhibit the activity of CTGF, a common factor in fibrotic and proliferative disorders characterized by persistent and excessive scarring that can lead to organ dysfunction and failure. This trial will assess pamrevlumab’s effect on patient time to and on ventilatory support, currently the most urgent need, and its potential to reduce mortality and fibrotic sequelae in the lung.

FibroGen today also announced the planned initiation of two additional randomized, double-blind, placebo-controlled Phase 2 studies investigating the efficacy and safety of pamrevlumab versus standard of care in patients with severe COVID-19 infection in the United States.

  • The Investigational New Drug (IND) application for the first trial has been approved by the U.S. Food and Drug Administration (FDA), and it will assess the efficacy and safety of pamrevlumab in approximately 130 patients hospitalized with COVID-19 in the acute setting.

° This is a randomized, double-blind, placebo-controlled study, to assess the efficacy and safety of pamrevlumab in hospitalized patients with acute COVID-19 infection, in a 1:1 ratio.
° The primary efficacy assessment is the proportion of hospitalized COVID-19 patients who never receive mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO) and remain alive at day 28.

  • The second planned U.S. trial, under discussion with the FDA, is expected to assess the longer term efficacy and safety of pamrevlumab in patients who recovered or are recovering from COVID-19 infection with evidence of interstitial lung disease.    

“Given our expertise in CTGF biology and its potential application in lung disease, we have a unique approach to the treatment of patients suffering from severe pulmonary involvement of COVID-19. The Italy and U.S. trials will determine if pamrevlumab treatment of hospitalized COVID-19 patients improves patient outcomes, both during the acute phase of infection and longer term with improved outcomes in interstitial lung disease,” said Enrique Conterno, Chief Executive Officer, FibroGen. “In these devastating times, we are grateful for the collaboration of health authorities, health care providers, and patients in enabling the conduct of these trials.”

https://fibrogen.gcs-web.com/news-releases/news-release-details/fibrogen-announces-first-patient-enrolled-pamrevlumab-clinical

1...109110111...156Page 110 of 156

EDITOR PICKS

POPULAR POSTS

POPULAR CATEGORY

ABOUT US

LifeProNow provides guidance and high quality contents to help job seekers to get their dream Job. All the contents are written by experienced folks and peer reviewed by experts.

Contact us: [email protected]

FOLLOW US

© LifeProNow | All Rights Reserved