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Clinical R&D
Since almost everyone is infected with the RSV almost every year, adults have a fairly high background immunity. That makes it difficult to evaluate efficacy in this group. Measured antibody levels were comparable before and after immunization and between vaccine and placebo groups. In a subsequent study it must be demonstrated whether the vaccine is immunogenic to children. SANOFI TO ACQUIRE PRINCIPIA BIOPHARMA Sanofi and Principia Biopharma Inc. a late-stage biopharmaceutical company focused on developing treatments for immune-mediated diseases, entered into a definitive agreement under which Sanofi will acquire all of the outstanding shares of Principia for $100 per share in cash, which represents an aggregate equity value of approximately $3.68 billion (on a fully diluted basis). The Sanofi and Principia Boards of Directors unanimously approved the transaction. Principia's Bruton tyrosine kinase (BTK) inhibitors add to Sanofi's efforts to accelerate and build a portfolio of the next generation of transformative treatments for autoimmune diseases. BTK is present in the signaling pathways of key innate and adaptive cell types of the immune system. Being able to block or disrupt these signaling processes can help in stopping inflammation and tissue destruction related to autoimmune diseases and target some of the underlying pathophysiology. • BTK inhibitor '168: In a Phase 2b study in patients with multiple sclerosis, '168 reduced Gd-enhancing T1 hyperintense lesions by 85% compared to placebo. In June, Sanofi announced the first multiple sclerosis patient was enrolled in the Phase 3 program for the BTK inhibitor, comprising four pivotal clinical trials across the disease spectrum. The Principia acquisition will provide an opportunity to expand the development program to evaluate indications beyond central nervous system diseases. • Rilzabrutinib: This oral BTK inhibitor is currently being evaluated in a Phase 3 program for patients with moderate to severe pemphigus, a rare, debilitating autoimmune disease that causes blistering of the skin and mucous membranes. A Phase 3 program for immune thrombocytopenia, a disease that causes high risk for bleeding events, is expected to be initiated by the end of 2020, assuming no COVID-19 related
impact. The company also has an ongoing Phase 2 program for IgG4-related diseases, which is driven by chronic inflammation, immune cell infiltration, and fibrosis within organs that can lead to severe morbidity. • PRN473 Topical: This BTK inhibitor is a topical agent currently in Phase 1 trials and is being developed for immune-mediated diseases that could benefit from localized application to the skin. The Principia BTK inhibitor franchise is based on its proprietary Tailored Covalency® platform that has generated potential best-in-class clinical candidates. The platform allows the design of both reversible covalent and irreversible covalent small molecule inhibitors that are more selective with less off-target effects. The optimized target residence time has potential to deliver a desired efficacy with a stronger safety profile. In 2017, Sanofi formed a collaboration with Principia under which Principia granted Sanofi an exclusive, worldwide license to develop and commercialize BTK inhibitor '168 in multiple sclerosis and other central nervous system diseases. GENMAB ANNOUNCES EUROPEAN MYELOMA NETWORK AND JANSSEN ACHIEVE POSITIVE TOPLINE RESULTS Genmab A/S (Nasdaq: GMAB) has announced that the European Myeloma Network (EMN) in collaboration with Janssen Research & Development, LLC (Janssen) reported positive results from the Phase 3 APOLLO (MMY3013) study of the subcutaneous (SC) formulation of daratumumab in combination with pomalidomide and dexamethasone (Pd) versus Pd alone as treatment for patients with relapsed or refractory multiple myeloma who have previously been treated with lenalidomide (an immunomodulatory drug) and a proteasome inhibitor (PI). The study met the primary endpoint of improving progression-free survival (PFS). Overall, the safety profile of daratumumab SC in combination with Pd was consistent with the safety profile for each therapy separately. "We are pleased with these positive results for daratumumab, administered as a subcutaneous formulation, in combination with pomalidomide and dexamethasone. The corresponding intravenous regimen was previously approved by the U.S. FDA based on the Phase1
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single-arm EQUULEUS study," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. Janssen Biotech, Inc., which obtained an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab in 2012, intends to discuss the data with health authorities in preparation for regulatory submissions and plans to submit the data for presentation at an upcoming medical conference. The APOLLO study was designed to confirm the results from the Phase 1 EQUULEUS (MMY1001) study, which investigated intravenous (IV) daratumumab plus Pd in the same indication. In June 2017, the U.S. Food and Drug Administration (U.S. FDA) approved the use of DARZALEX in combination with Pd for the treatment of patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a PI based on the results of the EQUULEUS study. VIIV HEALTHCARE ANNOUNCES DATA DEMONSTRATING THE FEASIBILITY OF DOVATO (DOLUTEGRAVIR/LAMIVUDINE) ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer Inc. and Shionogi Limited as shareholders, has announced findings from the STAT study, a phase IIIb, multi-centre, open label, single arm, 48-week study in the United States presented at the American Conference for the Treatment of HIV (ACTHIV) 2020. The study evaluated Dovato (dolutegravir/lamivudine) for rapid initiation of treatment after diagnosis in adults with HIV-1. Dovato was found to be effective and well tolerated in this setting, indicating the feasibility of its use in Test and Treat strategies. The STAT study followed a rapid Test and Treat model of care increasingly seen in clinical practice, with treatment initiated within 14 days of diagnosis before baseline HBV co-infection status, renal function and resistance test results were available. All study participants were tested for HBV co-infection prior to receiving Dovato, with results available after initiation of treatment. In the study, 92% (n=102/111) of participants with available data at 24 weeks, achieved a viral load of <50c/mL. This includes participants who stayed on Dovato and those who switched to alternative ART. Eight participants switched from Dovato to an alternative antiretroviral (ART) regimen; five of the eight due to HBV co-infection and one due to baseline resistance to lamivudine. Data were available for five of
these participants and showed that they all achieved a viral load of <50c/mL at 24 weeks, without developing HBV or HIV resistanceassociated mutations,1 indicating that rapid initiation of Dovato did not compromise outcomes for this subset of participants. 87% (n=97/111) of participants with available data at Week 24 and still taking Dovato* achieved a viral load of <50c/mL. At the start of the study, 8% (n=10) of participants had HIV-1 RNA >1,000,000 c/mL. At week 24, 80% (n=8) of these participants had HIV-1 RNA <50 c/mL. Kimberly Smith, MD, MPH, Head of Research & Development at ViiV Healthcare, said: “The results from the STAT study reinforce the proven efficacy of Dovato and provide further evidence supporting its use in settings where rapid treatment initiation is the standard. The STAT study also shows us that this treatment can be initiated when the baseline HBV co-infection or resistance status is unknown, as appropriate therapy adjustments can be made once results become available without compromising patient safety. These findings represent an important step forward in our understanding of current treatment options that can be rapidly initiated after an HIV diagnosis and confirm the validity of this approach with Dovato.” At 24 weeks, 11% (n=15) of participants discontinued the study, including 9% (n=12) who were lost to follow-up or withdrew consent and 2% (n=3) due to physician decision. Data were not available at week 24 for 4% (n=5) of participants. The study found that Dovato was well tolerated, with low rates of grade 2-5 drugrelated AEs (2%, n=2) and serious AEs (2%, n=2). About Dovato (dolutegravir/ lamivudine) Dovato is a once-daily, singlepill, 2-drug regimen (2DR) that combines the integrase strand transfer inhibitor (INI) dolutegravir (Tivicay, 50 mg) with the NRTI lamivudine (Epivir, 300 mg). Observed analysis, where missing patients were not included in the analysis Dovato (dolutegravir 50 mg/ lamivudine 300 mg tablets) is authorised in the EU for the treatment of HIV-1 infection in adults and adolescents above 12 years of age weighing at least 40 kg, with no known or suspected resistance to the INI class, or lamivudine.