The acquisition is a strategic fit for Sanofi, given the company’s growth in immune-mediated diseases and disease-modifying therapies in areas of high unmet need, as well as its diabetes expertise. Sanofi will continue to leverage its diabetes expertise to maximize TZIELD’s potential as a transformative therapy both globally and in the United States, with the goal of delaying the onset of Stage 3 type 1 diabetes in some of the approximately 65K people diagnosed each year. The acquisition expands on an existing co-promotion agreement with Provention Bio, which already provides TZIELD to patients in need of this immune-mediated therapy.
USFDA Committee Votes in Favor of Clinical Benefit of Roche’s Polivy
The Oncologic Drugs Advisory Committee (ODAC) of the United States Food and Drug Administration (FDA) voted 11 to 2 in favor of Polivy® (polatuzumab vedotin-piiq) in combination with Rituxan® (rituximab) plus cyclophosphamide, doxorubicin, and prednisone (R-CHP) for the treatment of people with previously untreated diffuse large B-cell lymphoma (DLBCL). Although the recommendations are not binding, the ODAC provides the FDA with independent opinions and recommendations from outside medical experts. By 2 April 2023, the FDA is expected to make a final decision on its review of Polivy’s supplemental Biologics License Application (sBLA) in this indication.
“Today’s committee decision to recognize the potential of this Polivy combination as a first-line treatment option is significant because four out of ten people with diffuse large B-cell lymphoma relapse or do not respond to initial treatment,” said Levi Garraway, M.D., Ph.D., Chief Medical Officer and Head of Global Product Development at Roche. “We believe that the clinical benefit demonstrated in the POLARIX study may improve outcomes for many people with newly diagnosed DLBCL, and we look forward to working with the FDA to make this treatment option available in the United States.”
This Polivy combination has been approved for the treatment of adult patients with previously untreated DLBCL in over 60 countries, including the EU, UK, Japan, Canada, and China. Polivy plus R-CHP was recently added to the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®) as a category 1 preferred regimen for first-line DLBCL treatment. Polivy plus R-CHP is the first treatment in 20 years to significantly improve progression-free survival (PFS) over the standard of care, MabThera/Rituxan plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).
The sBLA submission is based on pivotal data from the phase III POLARIX study, which demonstrated a statistically significant and clinically meaningful improvement in PFS with Polivy plus R-CHP in first-line DLBCL compared to standard-of-care R-CHOP. Polivy, in combination with bendamustine and MabThera/Rituxan, is currently approved in over 80 countries for the treatment of adults with relapsed or refractory DLBCL after one or more prior therapies, including in the United States under FDA accelerated approval, as a readily available, fixed-duration treatment option.
FDA Agrees to Review Mesoblast’s GvHD drug again
Mesoblast Limited, a global leader in allogeneic cellular medicines for inflammatory diseases, announced that the FDA’s Office of Therapeutic Products (OTP) has accepted the Company’s Biologics License Application (BLA) resubmission for remestemcel-L in the treatment of children with steroid-refractory acute graft versus host disease (SR-aGVHD). The FDA considers the resubmission to be a complete response and has set an August 2, 2023, Prescription Drug User Fee Act (PDUFA) goal date.
“Over the last two years, we have worked tirelessly to address the issues raised by the FDA. “We look forward to working closely with the Agency during the review period to make remestemcel-L available as a therapy for children suffering from SR-aGVHD,” said Mesoblast Chief Executive Silviu Itescu.
Survival outcomes for the most severe forms of SRaGVHD, a life-threatening complication of an allogeneic bone marrow transplant following treatment for blood cancers and other conditions, have not improved over the last two decades. 1-3 Because there are no approved GvHD treatments for children under the age of 12, there is an urgent need for a therapy that improves the dismal survival rates. If remestemcelL is approved by the FDA, it will be the first allogeneic “off-the-shelf” cellular medicine approved in the United States, as well as the first therapy for children under the age of 12 with SR-aGVHD.
The resubmission contains the following new information:
- new long-term survival data for children enrolled in the Phase 3 trial for at least four years,
- new outcome data following remestemcel-L use in high-risk disease activity and on survival using propensity-matching of children in the Phase 3 trial and controls stratified by validated biomarkers,
- new analyses of prospectively obtained data relating the validated potency assay, which was used to release product for the Phase 3 clinical trial and reflects the primary mechanism of action, to in vivo bioactivity and overall survival,
- new analyses of prospectively obtained clinical data relating manufacturing changes implemented during product development prior to Phase III, to progressive increases in potency and improved survival outcomes of children with SR-aGVHD treated with remestemcel-L under expanded access,
- new data demonstrating that the validated potency assay has low variability and can adequately demonstrate manufacturing consistency and reproducibility, and
- development of a new commercial product specification based on extensive clinical data to provide assurance that future batches of remestemcel-L will have attributes supportive of expected survival outcomes.
The FDA granted remestemcel-L Fast Track designation, which is given to drugs that treat a serious condition and provide a significant improvement in safety or effectiveness over existing treatments, as well as Priority Review designation, which is given to drugs that treat a serious condition and provide a significant improvement in safety or effectiveness over existing treatments.
FDA Approves Acadia’s Daybue for Rett syndrome
On March 10, 2023, Acadia Pharmaceuticals Inc. announced that the U.S. Food and Drug Administration (FDA) had approved DAYBUE™ (trofinetide) for the treatment of Rett syndrome in adult and pediatric patients two years of age and older. DAYBUE is the first and only drug approved for treating Rett syndrome. Acadia’s Trofinetide is a synthetic version of a naturally occurring molecule known as the tripeptide glycine-proline-glutamate (GPE). The mechanism by which trofinetide exerts therapeutic effects in patients with Rett syndrome is unknown.
Upon achieving the historic landmark, Steve Davis, Acadia’s Chief Executive Officer, has said, “Today marks an important milestone for the Rett community and Acadia. As the first FDA-approved drug for the treatment of Rett syndrome, DAYBUE now offers the potential to make meaningful differences in the lives of patients and their families who have lacked options to treat the diverse and debilitating array of symptoms caused by Rett syndrome.”
In 2018, Acadia entered into an exclusive license agreement with Neuren Pharmaceuticals Limited (ASX: NEU) for the development and commercialization of trofinetide for the treatment of Rett syndrome and other indications in North America. As per the updates from Acadia, DAYBUE is expected to hit the US market by the end of April 2023.
Rett syndrome is a unique neurodevelopmental disorder that is first noticed in infancy and primarily affects girls, but can be rarely seen in boys. It is caused by mutations on the X-chromosome on a gene called MECP2. As per the estimate, about 6,000 to 9,000 patients in the US are affected with Rett syndrome, with a diagnosed population of approximately 4,500. Treatment for Rett syndrome is symptomatic, i.e., focusing on the management of symptoms, that require a multidisciplinary approach. Treatment basically is categorized into physical therapy, hydrotherapy, occupational therapy, speech-language therapy and medications. The approval and the launch of Daybue is anticipated to have a positive impact on the Rett syndrome treatment dynamics.
FDA Approves Nelarabine Injection for T-cell Leukemia and Lymphoma
On March 07, 2023, Shorla Oncology (‘Shorla’) announced that the US FDA had approved the company’s oncology drug, Nelarabine Injection, for the treatment of T-cell Acute Lymphoblastic Leukemia (T-ALL) and T-cell Lymphoblastic Lymphoma (T-LBL). The approval of Nelarabine Injection provides patients with an alternative to a product that has historically been in shortage. Moreover, it also marks the first product approved in the US market for Shorla.
Shorla specializes in developing innovative oncology drugs with a focus on orphan and pediatric cancers. With strong support from scientists and clinicians, the company has an advanced pipeline of oncology therapies to treat a number of unmet patient needs. Earlier, on Aug 17, 2021, Shorla and EVERSANA™ announced a partnership to support the launch and commercialization of Shorla’s oncology portfolio. The partnership initially focuses on SH-111, an oncology drug designed to treat T-cell leukemia, currently pending U.S. FDA approval.
On this occasion, Sharon Cunningham, CEO and Co-founder of Shorla Oncology, said, “we are very proud to see our research in oncology innovation and dedication to patient care culminate in this US FDA approval. Nelarabine Injection is a critical treatment for patients living with T-cell leukemia, particularly for children with leukemia, and it is our hope that today’s approval addresses the clinical need in this patient community.”
Added Orlaith Ryan, CTO and Co-founder of Shorla Oncology, stated, “We are honored to bring this much-needed product to patients in the U.S. and hopefully to patients worldwide in the near future. This milestone further fuels our passion and commitment to develop innovative oncology treatments, with a focus on rare cancers where existing treatments are limited, in short supply, or inadequate.”
T-cell leukemia is an aggressive blood and bone marrow cancer that progresses quickly. While most leukemia targets older people, T-cell leukemia is most common among children, with this particular treatment often in shortage. The approval of Nelarabine Injection is expected to impact treatment access and patient care significantly. As per DelveInsight, in addition to Shorla Oncology, more than 15+ key players are actively working on 15+ emerging therapies in the T-cell leukemia therapeutics market. Several of the therapeutic candidates are in various stages of clinical development. The launch of these emerging therapies is also expected to immensely improve overall T-cell leukemia treatment dynamics in the coming years.
Calliditas Announces Primary Endpoint Successfully Met in Phase 3 NefIgArd Trial Evaluating Nefecon® in IgA Nephropathy
On March 13, 2023, Calliditas Therapeutics AB announced positive topline results from the global, randomized, double-blind, placebo-controlled Phase 3 clinical trial NefIgArd, investigating the effect of Nefecon (TARPEYO®/Kinpeygo® (budesonide) delayed release capsules) versus placebo in patients with primary IgA nephropathy (IgAN).
As per the updates from Calliditas, the trial met its primary endpoint with Nefecon demonstrating a highly statistically significant benefit over placebo in estimated glomerular filtration rate (eGFR) over the two-year period of 9-months of treatment with Nefecon or placebo and 15-months of follow-up off the drug. Supportive 2-year total slope analyses were statistically significant and clinically meaningful, reflecting a sustained treatment benefit. UPCR reductions observed were durable, reflecting a long-lasting treatment effect during the 15-month follow-up period off treatment.
Renée Aguiar-Lucander, CEO, has said, “this is truly a great outcome for IgAN patients. This reflects sustained impact on kidney function across the entire study population with a treatment which was specifically designed to treat IgAN by downregulating pathogenic IgA1 antibodies at their presumed source, and we believe this dataset supports regulatory filing for full approval based on the Phase 3 study population”.
Earlier based on the Part A data, Calliditas received accelerated approval from the US FDA in December 2021 and conditional marketing authorization from the European Commission (EC) in July 2022, marking the first time a drug was approved for the treatment of IgAN in the US and the European Economic Area (EEA). Nefecon is being marketed by Calliditas in the US under the brand name TARPEYO®, and by STADA Arzneimittel AG in the EEA, Switzerland, and the UK under the brand name Kinpeygo®. On the basis of the data, Calliditas plans to file for full approval from the FDA and support filing for full approval with EC and UK MHRA during 2023 for patients with primary IgAN based on the Phase 3 study population. IgA nephropathy is one of the most common kidney diseases. While people of any age, gender or ethnicity can have it, the disease is more common in men than in women.
As per DelveInsight’s estimates, in 2021, the total prevalent cases of IgAN in the 7MM were approximately 400,000 cases, among which the United States recorded the highest number of cases with approximately 135,000, and lowest in Spain with around 20,000 cases. To meet the need for disease-specific targeted treatments with novel MOA, in addition to Nefecon, there are a few promising therapies in development by major pharma and biotech giants such as Omeros, Chinoo
