Patient preferences for the treatment of paroxysmal nocturnal hemoglobinuria: Interim results of a patient survey of ravulizumab (ALXN1210) and eculizumab

BACKGROUND: Eculizumab inhibits complement-mediated hemolysis and thrombosis and improves quality of life (QoL) in patients with paroxysmal nocturnal hemoglobinuria (PNH). However, eculizumab has a treatment burden associated with every 2-week dosing. Ravulizumab, a new C5 inhibitor for PNH administered every 8 weeks, was shown to be non-inferior to eculizumab in 2 phase 3 trials. In the presence of multiple treatment options, patient preference should be considered when selecting a treatment plan. OBJECTIVE: To evaluate patient treatment preference for eculizumab or ravulizumab in clinical sub-study ALXN1210-PNH-302s. METHODS: ALXN1210-PNH-302 sub-study aims to enroll at least 95 PNH patients. Patients were enrolled from the ALXN1210-PNH-302 extension study, had received at least 2 doses of ravulizumab and provided informed consent. All patients were on stable eculizumab therapy prior to entering the trial. Patient treatment preference was evaluated at one time point by using an 11-item PNH specific patient preference questionnaire (PNH-PPQ). RESULTS: To date, 52 completed PNH-PPQs have been analyzed. Mean age was 50 years (range: 28-78) and sex was equally distributed (~50%). Mean time since diagnosis was 15 years (range: 2-48) and the mean number of days between the last randomized study treatment and the survey was 278. Overall, 94% of patients (n = 49) preferred ravulizumab vs. 6% (n = 3; P \u3c 0.001) who preferred eculizumab (n = 1) or had no preference (n = 2). When asked for drug preference, ravulizumab was preferred based on frequency of infusions (98%), ability to plan activities (98%), convenience of receiving treatment (92%), overall QoL (88%), and effectiveness of medication until the next infusion (79%). When asked for the most important characteristic for treatment preference, the most common choice was frequency of infusions (42%). Moderate to large effect sizes were observed for factors differentiating ravulizumab and eculizumab, including the frequency of infusions disrupting everyday life (-1.43, P \u3c 0.001), feeling fatigued after infusions (-0.61, P \u3c 0.001), and being able to enjoy life while receiving treatment (0.96, P \u3c 0.001). CONCLUSIONS: This interim analysis provides insights into PNH patient treatment preferences, and indicates that the vast majority of patients surveyed preferred ravulizumab due to reduced infusion frequency, ability to plan activities, effectiveness of medication, and convenience of treatment compared to eculizumab

Long-term safety and efficacy of ravulizumab in patients with paroxysmal nocturnal hemoglobinuria: 2-year results from two pivotal phase 3 studies

10.1111/ejh.13783European Journal of Haematology1093205-21

Observation of the Bs0 ⁣→D∗+D∗−B^0_s\!\to D^{*+}D^{*-} decay

International audienceThe first observation of the ${B}_s^0$→ D$^{∗+}$D$^{∗−}$ decay and the measurement of its branching ratio relative to the B$^{0}$→ D$^{∗+}$D$^{∗−}$ decay are presented. The data sample used corresponds to an integrated luminosity of 9 fb$^{−1}$ of proton-proton collisions recorded by the LHCb experiment at centre-of-mass energies of 7, 8 and 13 TeV between 2011 and 2018. The decay is observed with more than 10 standard deviations and the time-integrated ratio of branching fractions is determined to be$\frac{\mathcal{B}\left({B}_s^0\to {D}^{\ast +}{D}^{\ast -}\right)}{\mathcal{B}\left({B}^0\to {D}^{\ast +}{D}^{\ast -}\right)}=0.269\pm 0.032\pm 0.011\pm 0.008,$where the first uncertainty is statistical, the second systematic and the third due to the uncertainty of the fragmentation fraction ratio f$_{s}$/f$_{d}$. The ${B}_s^0$→ D$^{*+}$D$^{*−}$ branching fraction is calculated to be$\mathcal{B}\left({B}_s^0\to {D}^{\ast +}{D}^{\ast -}\right)=\left(2.15\pm 0.26\pm 0.09\pm 0.06\pm 0.16\right)\times {10}^{-4},$where the fourth uncertainty is due to the B$^{0}$→ D$^{*+}$D$^{*−}$ branching fraction. These results are calculated using the average ${B}_s^0$ meson lifetime in simulation. Correction factors are reported for scenarios where either a purely heavy or a purely light ${B}_s^0$ eigenstate is considered.[graphic not available: see fulltext

A study of C ⁣PC\!P violation in the decays B±→[K+K−π+π−]Dh±B^\pm\to[K^+K^-\pi^+\pi^-]_D h^{\pm} (h=K,πh = K, \pi) and B±→[π+π−π+π−]Dh±B^\pm\to[\pi^+\pi^-\pi^+\pi^-]_D h^{\pm}

The first study of $C\!P$ violation in the decay mode $B^\pm\to[K^+K^-\pi^+\pi^-]_D h^{\pm}$, with $h=K,\pi$, is presented, exploiting a data sample of proton-proton collisions collected by the LHCb experiment that corresponds to an integrated luminosity of $9$ fb$^{-1}$. The analysis is performed in bins of phase space, which are optimised for sensitivity to local $C\!P$ asymmetries. $C\!P$-violating observables that are sensitive to the angle $\gamma$ of the Unitarity Triangle are determined. The analysis requires external information on charm-decay parameters, which are currently taken from an amplitude analysis of LHCb data, but can be updated in the future when direct measurements become available. Measurements are also performed of phase-space integrated observables for $B^\pm\to[K^+K^-\pi^+\pi^-]_D h^{\pm}$ and $B^\pm\to[\pi^+\pi^-\pi^+\pi^-]_D h^{\pm}$ decays.The first study of $C\!P$ violation in the decay mode {{B} ^\pm } \rightarrow [{{K} ^+} {{K} ^-} {{\uppi } ^+} {{\uppi } ^-} ]_{D} h^\pm , with $h=K,\pi$, is presented, exploiting a data sample of proton–proton collisions collected by the LHCb experiment that corresponds to an integrated luminosity of $9\text {\,fb} ^{-1}$. The analysis is performed in bins of phase space, which are optimised for sensitivity to local $C\!P$ asymmetries. $C\!P$-violating observables that are sensitive to the angle $\gamma$ of the Unitarity Triangle are determined. The analysis requires external information on charm-decay parameters, which are currently taken from an amplitude analysis of LHCb data, but can be updated in the future when direct measurements become available. Measurements are also performed of phase-space integrated observables for {{B} ^\pm } \rightarrow [{{K} ^+} {{K} ^-} {{\uppi } ^+} {{\uppi } ^-} ]_{D} h^\pm and {{B} ^\pm } \rightarrow [{{\uppi } ^+} {{\uppi } ^-} {{\uppi } ^+} {{\uppi } ^-} ]_{D} h^\pm decays.The first study of $C\!P$ violation in the decay mode $B^\pm\to[K^+K^-\pi^+\pi^-]_D h^\pm$, with $h=K,\pi$, is presented, exploiting a data sample of proton-proton collisions collected by the LHCb experiment that corresponds to an integrated luminosity of $9$ fb$^{-1}$. The analysis is performed in bins of phase space, which are optimised for sensitivity to local $C\!P$ asymmetries. $C\!P$-violating observables that are sensitive to the angle $\gamma$ of the Unitarity Triangle are determined. The analysis requires external information on charm-decay parameters, which are currently taken from an amplitude analysis of LHCb data, but can be updated in the future when direct measurements become available. Measurements are also performed of phase-space integrated observables for $B^\pm\to[K^+K^-\pi^+\pi^-]_D h^\pm$ and $B^\pm\to[\pi^+\pi^-\pi^+\pi^-]_D h^\pm$ decays

Measurement of the <math display="inline"><mrow><msubsup><mrow><mi mathvariant="normal">Λ</mi></mrow><mrow><mi>b</mi></mrow><mrow><mn>0</mn></mrow></msubsup><mo stretchy="false">→</mo><mi mathvariant="normal">Λ</mi><mo stretchy="false">(</mo><mn>1520</mn><mo stretchy="false">)</mo><msup><mrow><mi>μ</mi></mrow><mrow><mo>+</mo></mrow></msup><msup><mrow><mi>μ</mi></mrow><mrow><mo>-</mo></mrow></msup></mrow></math> Differential Branching Fraction

The branching fraction of the rare decay $\Lambda_{b}^{0}\to \Lambda(1520) \mu^{+}\mu^{-}$ is measured for the first time, in the squared dimuon mass intervals, $q^2$, excluding the $J/\psi$ and $\psi(2S)$ regions. The data sample analyzed was collected by the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV, corresponding to a total integrated luminosity of $9\,\mathrm{fb}^{-1}$. The result in the highest $q^{2}$ interval, $q^{2} > 15.0\,\mathrm{GeV}^2/c^4$, where theoretical predictions have the smallest model dependence, agrees with the predictions.The branching fraction of the rare decay Λb0→Λ(1520)μ+μ- is measured for the first time, in the squared dimuon mass intervals q2, excluding the J/ψ and ψ(2S) regions. The data sample analyzed was collected by the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV, corresponding to a total integrated luminosity of 9  fb-1. The result in the highest q2 interval, q2&gt;15.0  GeV2/c4, where theoretical predictions have the smallest model dependence, agrees with the predictions.The branching fraction of the rare decay $\Lambda_{b}^{0}\to \Lambda(1520) \mu^{+}\mu^{-}$ is measured for the first time, in the squared dimuon mass intervals, $q^2$, excluding the $J/\psi$ and $\psi(2S)$ regions. The data sample analyzed was collected by the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV, corresponding to a total integrated luminosity of $9\ \mathrm{fb}^{-1}$. The result in the highest $q^{2}$ interval, $q^{2} >15.0\ \mathrm{GeV}^2/c^4$, where theoretical predictions have the smallest model dependence, agrees with the predictions

Study of Bc+→χcπ+B_c^+ \rightarrow \chi_c \pi^+ decays

International audienceA study of $B_c^+ \rightarrow \chi_c \pi^+$ decays is reported using proton-proton collision data, collected with the LHCb detector at centre-of-mass energies of 7, 8, and 13 TeV, corresponding to an integrated luminosity of 9fb$^{-1}$. The decay $B_c^+ \rightarrow \chi_{c2} \pi^+$ is observed for the first time, with a significance exceeding seven standard deviations. The relative branching fraction with respect to the $B_c^+ \rightarrow J/\psi \pi^+$ decay is measured to be $$\frac{\mathcal{B}_{B_c^+ \rightarrow \chi_{c2} \pi^+}} {\mathcal{B}_{B_c^+ \rightarrow J/\psi \pi^+}} = 0.37 \pm 0.06 \pm 0.02 \pm 0.01 ,$$ where the first uncertainty is statistical, the second is systematic, and the third is due to the knowledge of the $\chi_c \rightarrow J/\psi \gamma$ branching fraction. No significant $B_c^+ \rightarrow \chi_{c1} \pi^+$ signal is observed and an upper limit for the relative branching fraction for the $B_c^+ \rightarrow \chi_{c1} \pi^+$ and $B_c^+ \rightarrow \chi_{c2} \pi^+$ decays of $$\frac{\mathcal{B}_{B_c^+ \rightarrow \chi_{c1} \pi^+}} {\mathcal{B}_{B_c^+ \rightarrow \chi_{c2} \pi^+}} < 0.49$$ is set at the 90% confidence level

Test of lepton flavour universality using B0→D∗−τ+ντB^0 \to D^{*-}\tau^+\nu_{\tau} decays with hadronic τ\tau channels

The branching fraction $\mathcal{B}(B^0 \to D^{*-}\tau^+\nu_\tau)$ is measured relative to that of the normalisation mode $B^0 \to D^{*-}\pi^+\pi^-\pi^+$ using hadronic $\tau^+ \to \pi^+\pi^-\pi^+(\pi^0)\bar{\nu}_\tau$ decays in proton-proton collision data at a centre-of-mass energy of 13 TeV collected by the LHCb experiment, corresponding to an integrated luminosity of 2 fb$^{-1}$. The measured ratio is $\mathcal{B}(B^0 \to D^{*-}\tau^+\nu_\tau)/\mathcal{B}(B^0 \to D^{*-}\pi^+\pi^-\pi^+)= 1.70 \pm 0.10^{+0.11}_{-0.10}$, where the first uncertainty is statistical and the second is related to systematic effects. Using established branching fractions for the $B^0 \to D^{*-}\pi^+\pi^-\pi^+$ and $B^0 \to D^{*-} \mu^+\nu_\mu$ modes, the lepton universality test, $\mathcal{R}(D^{*-}) \equiv \mathcal{B}(B^0 \to D^{*-}\tau^+\nu_\tau)/\mathcal{B}(B^0 \to D^{*-} \mu^+\nu_\mu)$ is calculated, $$\mathcal{R}(D^{*-}) = 0.247 \pm 0.015 \pm 0.015 \pm 0.012\, ,$$ where the third uncertainty is due to the uncertainties on the external branching fractions. This result is consistent with the Standard Model prediction and with previous measurements.The branching fraction B(B0→D*-τ+ντ) is measured relative to that of the normalization mode B0→D*-π+π-π+ using hadronic τ+→π+π-π+(π0)ν¯τ decays in proton-proton collision data at a center-of-mass energy of 13 TeV collected by the LHCb experiment, corresponding to an integrated luminosity of 2  fb-1. The measured ratio is B(B0→D*-τ+ντ)/B(B0→D*-π+π-π+)=1.70±0.10-0.10+0.11, where the first uncertainty is statistical and the second is related to systematic effects. Using established branching fractions for the B0→D*-π+π-π+ and B0→D*-μ+νμ modes, the lepton universality test R(D*-)≡B(B0→D*-τ+ντ)/B(B0→D*-μ+νμ) is calculated, R(D*-)=0.247±0.015±0.015±0.012, where the third uncertainty is due to the uncertainties on the external branching fractions. This result is consistent with the Standard Model prediction and with previous measurements.The branching fraction $\mathcal{B}(B^0 \to D^{*-}\tau^+\nu_{\tau})$ is measured relative to that of the normalisation mode $B^0 \to D^{*-}\pi^+\pi^-\pi^+$ using hadronic $\tau^+ \to \pi^+\pi^-\pi^+(\pi^0)\bar{\nu}_{\tau}$ decays in proton-proton collision data at a centre-of-mass energy of 13 TeV collected by the LHCb experiment, corresponding to an integrated luminosity of 2 fb$^{-1}$. The measured ratio is $\mathcal{B}(B^0 \to D^{*-}\tau^+\nu_{\tau})/\mathcal{B}(B^0 \to D^{*-}\pi^+\pi^-\pi^+)= 1.70 \pm 0.10^{+0.11}_{-0.10}$, where the first uncertainty is statistical and the second is related to systematic effects. Using established branching fractions for the $B^0 \to D^{*-}\pi^+\pi^-\pi^+$ and $B^0 \to D^{*-} \mu^+\nu_\mu$ modes, the lepton universality test, $\mathcal{R}(D^{*-}) \equiv \mathcal{B}(B^0 \to D^{*-}\tau^+\nu_{\tau})/\mathcal{B}(B^0 \to D^{*-} \mu^+\nu_\mu)$ is calculated, $$\mathcal{R}(D^{*-}) = 0.247 \pm 0.015 \pm 0.015 \pm 0.012\, ,$$ where the third uncertainty is due to the uncertainties on the external branching fractions. This result is consistent with the Standard Model prediction and with previous measurements

First observation and branching fraction measurement of the Λb0→Ds−p {\Lambda}_b^0\to {D}_s^{-}p decay

International audienceThe first observation of the ${\Lambda}_b^0\to {D}_s^{-}p$ decay is presented using proton-proton collision data collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}$ = 13 TeV, corresponding to a total integrated luminosity of 6 fb$^{−1}$. Using the ${\Lambda}_b^0\to {\Lambda}_c^{+}{\pi}^{-}$ decay as the normalisation mode, the branching fraction of the ${\Lambda}_b^0\to {D}_s^{-}p$ decay is measured to be $\mathcal{B}\left({\Lambda}_b^0\to {D}_s^{-}p\right)=\left(12.6\pm 0.5\pm 0.3\pm 1.2\right)\times {10}^{-6}$, where the first uncertainty is statistical, the second systematic and the third due to uncertainties in the branching fractions of the ${\Lambda}_b^0\to {\Lambda}_c^{+}{\pi}^{-}$, ${D}_s^{-}\to {K}^{-}{K}^{+}{\pi}^{-}$ and ${\Lambda}_c^{+}\to p{K}^{-}{\pi}^{+}$ decays.[graphic not available: see fulltext

Observation of a resonant structure near the Ds+Ds−D_s^+ D_s^- threshold in the B+→Ds+Ds−K+B^+\to D_s^+ D_s^- K^+ decay

An amplitude analysis of the $B^+\to D_s^+ D_s^- K^+$ decay is carried out to study for the first time its intermediate resonant contributions, using proton-proton collision data collected with the LHCb detector at centre-of-mass energies of 7, 8 and 13 TeV. A near-threshold peaking structure, referred to as $X(3960)$, is observed in the $D_s^+ D_s^-$ invariant-mass spectrum with significance greater than 12 standard deviations. The mass, width and the quantum numbers of the structure are measured to be $3956\pm5\pm10$ MeV, $43\pm13\pm8$ MeV and $J^{PC}=0^{++}$, respectively, where the first uncertainties are statistical and the second systematic. The properties of the new structure are consistent with recent theoretical predictions for a state composed of $c\bar{c} s\bar{s}$ quarks. Evidence for an additional structure is found around 4140 MeV in the $D_s^+ D_s^-$ invariant mass, which might be caused either by a new resonance with the $0^{++}$ assignment or by a $J/\psi \phi\leftrightarrow D_s^+ D_s^-$ coupled-channel effect.An amplitude analysis of the B+→Ds+Ds-K+ decay is carried out to study for the first time its intermediate resonant contributions, using proton-proton collision data collected with the LHCb detector at center-of-mass energies of 7, 8, and 13 TeV. A near-threshold peaking structure, referred to as X(3960), is observed in the Ds+Ds- invariant-mass spectrum with significance greater than 12 standard deviations. The mass, width, and the quantum numbers of the structure are measured to be 3956±5±10  MeV, 43±13±8  MeV, and JPC=0++, respectively, where the first uncertainties are statistical and the second systematic. The properties of the new structure are consistent with recent theoretical predictions for a state composed of cc¯ss¯ quarks. Evidence for an additional structure is found around 4140 MeV in the Ds+Ds- invariant mass, which might be caused either by a new resonance with the 0++ assignment or by a J/ψϕ↔Ds+Ds- coupled-channel effect.An amplitude analysis of the $B^+\to D_s^+ D_s^- K^+$ decay is carried out to study for the first time its intermediate resonant contributions, using proton-proton collision data collected with the LHCb detector at centre-of-mass energies of 7, 8 and 13 TeV. A near-threshold peaking structure, referred to as $X(3960)$, is observed in the $D_s^+ D_s^-$ invariant-mass spectrum with significance greater than 12 standard deviations. The mass, width and the quantum numbers of the structure are measured to be $3956\pm5\pm10$ MeV, $43\pm13\pm8$ MeV and $J^{PC}=0^{++}$, respectively, where the first uncertainties are statistical and the second systematic. The properties of the new structure are consistent with recent theoretical predictions for a state composed of $c\bar{c}s\bar{s}$ quarks. Evidence for an additional structure is found around 4140 MeV in the $D_s^+ D_s^-$ invariant mass, which might be caused either by a new resonance with the $0^{++}$ assignment or by a $J/\psi \phi\leftrightarrow D_s^+ D_s^-$ coupled-channel effect