Showing papers by "Pharmaceutical Product Development published in 2017"
TL;DR: Despite high incidence of transient, mild-to-moderate injection-site reactions, long-acting cabotegravir was well tolerated with an acceptable safety profile and Pharmacokinetic data suggest that 800 mg administered every 12 weeks is a suboptimal regimen; alternative dosing strategies are being investigated.
173 citations
TL;DR: PF-04236921 was not significantly different from placebo for the primary efficacy end point in patients with SLE and evidence of an effect with 10 mg was seen in a post hoc analysis.
Abstract: Objectives This phase II trial evaluated the efficacy and safety of an interleukin (IL) 6 monoclonal antibody for systemic lupus erythematosus (SLE). Methods Patients with active disease were randomised to placebo or PF-04236921 10 mg, 50 mg or 200 mg, subcutaneously, every 8 weeks with stable background therapy. SLE Responder Index (SRI-4; primary end point) and British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) were assessed at week 24. Post hoc analysis identified an enriched population based upon planned univariate analyses. Results 183 patients received treatment (placebo, n=45; 10 mg, n=45; 50 mg, n=47; 200 mg, n=46). The 200 mg dose was discontinued due to safety findings and not included in the primary efficacy analysis. The SRI-4 response rates were not significant for any dose compared with placebo; however, the BICLA response rate was significant for 10 mg (p=0.026). The incidence of severe flares was significantly reduced with 10 mg (n=0) and 50 mg (n=2) combined versus placebo (n=8; p Conclusions PF-04236921 was not significantly different from placebo for the primary efficacy end point in patients with SLE. Evidence of an effect with 10 mg was seen in a post hoc analysis. Safety was acceptable for doses up to 50 mg as the 200 mg dose was discontinued due to safety findings. Trial registration number NCT01405196; Pre-results.
99 citations
TL;DR: A BRCA1 reversion mutation is reported in a patient newly diagnosed with triple-negative breast cancer that developed over 18 weeks of platinum-based neoadjuvant therapy that was associated with poor therapy response, early relapse, and death.
Abstract: Purpose: In germline BRCA1 or BRCA2 (BRCA1/2) mutation carriers, restoration of tumor BRCA1/2 function by a secondary mutation is recognized as a mechanism of resistance to platinum and PARP inhibitors, primarily in ovarian cancer. We evaluated this mechanism of resistance in newly diagnosed patients with BRCA1/2-mutant breast cancer with poor response to neoadjuvant platinum-based therapy.Experimental Design: PrECOG 0105 was a phase II neoadjuvant study of gemcitabine, carboplatin, and iniparib in patients with stage I-IIIA triple-negative or BRCA1/2 mutation-associated breast cancer (n = 80). All patients underwent comprehensive BRCA1/2 genotyping. For mutation carriers with moderate or extensive residual disease after neoadjuvant therapy, BRCA1/2 status was resequenced in the residual surgical breast tumor tissue.Results: Nineteen patients had a deleterious germline BRCA1/2 mutation, and four had moderate residual disease at surgery. BRCA1/2 sequencing of residual tissue was performed on three patients. These patients had BRCA1 1479delAG, 3374insGA, and W1712X mutations, respectively, with LOH at these loci in the pretreatment tumors. In the first case, a new BRCA1 mutation was detected in the residual disease. This resulted in a 14-amino acid deletion and restoration of the BRCA1 reading frame. A local relapse biopsy 4 months later revealed the identical reversion mutation, and the patient subsequently died from metastatic breast cancer.Conclusions: We report a BRCA1 reversion mutation in a patient newly diagnosed with triple-negative breast cancer that developed over 18 weeks of platinum-based neoadjuvant therapy. This was associated with poor therapy response, early relapse, and death. Clin Cancer Res; 23(13); 3365-70. ©2017 AACR.
47 citations
TL;DR: Fetinib demonstrated promising antitumor activity and good tolerability in the first-line setting in Asian advanced hepatocellular carcinoma patients in a single-arm study.
Abstract: Purpose: This phase I/II single-arm study evaluated the safety, pharmacokinetics, pharmacodynamics, and activity of foretinib, an oral multikinase inhibitor of MET, ROS, RON, AXL, TIE-2, and VEGFR2, in the first-line setting in advanced hepatocellular carcinoma patients.Experimental Design: In the phase I part, advanced hepatocellular carcinoma patients were dose escalated on foretinib (30-60 mg) every day using the standard 3+3 design. Once the maximum tolerated dose (MTD) was determined, an additional 32 patients were dosed at the MTD in the phase II expansion cohort for assessment of efficacy and safety. Exploratory analyses were conducted to assess potential biomarkers that might correlate with clinical efficacy and survival.Results: The MTD of foretinib was established as 30 mg every day. The most frequent adverse events were hypertension, decreased appetite, ascites, and pyrexia. When dosed at 30 mg every day in the first-line setting, foretinib demonstrated promising antitumor activity. According to the modified mRECIST, the objective response rate was 22.9%, the disease stabilization rate 82.9%, and the median duration of response 7.6 months. The median time to progression was 4.2 months and the median overall survival (OS) was 15.7 months. Fifteen candidate biomarkers whose levels in the circulation were significantly altered in response to foretinib treatment were elucidated. Multivariate analyses identified IL6 and IL8 as independent predictors of OS.Conclusions: Foretinib demonstrated promising antitumor activity and good tolerability in the first-line setting in Asian advanced hepatocellular carcinoma patients. Baseline plasma levels of IL6 or IL8 might predict the response to foretinib. Clin Cancer Res; 23(10); 2405-13. ©2016 AACR.
40 citations
TL;DR: This is the first large scale study to sequence glyco- and disulfide bonded MHCII peptides from the surface of cancer cells and could represent a novel avenue of tumor activation and/or immunoevasion.
Abstract: The MHC class II (MHCII) processing pathway presents peptides derived from exogenous or membrane-bound proteins to CD4+ T cells. Several studies have shown that glycopeptides are necessary to modulate CD4+ T cell recognition, though glycopeptide structures in these cases are generally unknown. Here, we present a total of 93 glycopeptides from three melanoma cell lines and one matched EBV-transformed line with most found only in the melanoma cell lines. The glycosylation we detected was diverse and comprised 17 different glycoforms. We then used molecular modeling to demonstrate that complex glycopeptides are capable of binding the MHC and may interact with complementarity determining regions. Finally, we present the first evidence of disulfide-bonded peptides presented by MHCII. This is the first large scale study to sequence glyco- and disulfide bonded MHCII peptides from the surface of cancer cells and could represent a novel avenue of tumor activation and/or immunoevasion.
35 citations
TL;DR: The Brighton Collaboration Respiratory Distress in the Neonate Working Group shows clear improvements in the quality of life for Neonate patients using a simple, scalable, and scalable approach.
35 citations
TL;DR: In women undergoing FET, day-6 vitrified embryo transfer is associated with a significantly lower risk of ectopic pregnancy than both day-3 and day-5 Vitrified embryo transfers.
35 citations
TL;DR: The experiments provide a framework to create a versatile technology platform for the development of ATCs for precise detection and treatment of ovarian cancer cells and showed that the ATC based on scFv-425 is suitable for the highly specific detection of EGFR+.
Abstract: Targeted theranostics is an alternative strategy in cancer management that aims to improve cancer detection and treatment simultaneously. This approach combines potent therapeutic and diagnostic agents with the specificity of different cell receptor ligands in one product. The success of antibody drug conjugates (ADCs) in clinical practice has encouraged the development of antibody theranostics conjugates (ATCs). However, the generation of homogeneous and pharmaceutically-acceptable ATCs remains a major challenge. The aim of this study is to detect and eliminate ovarian cancer cells on-demand using an ATC directed to EGFR. An ATC with a defined drug-to-antibody ratio was generated by the site-directed conjugation of IRDye®700 to a self-labeling protein (SNAP-tag) fused to an EGFR-specific antibody fragment (scFv-425). In vitro and ex vivo imaging showed that the ATC based on scFv-425 is suitable for the highly specific detection of EGFR+ ovarian cancer cell, human tissues and ascites samples. The construct was also able to eliminate EGFR+ cells and human ascites cells with IC50 values of 45–66 nM and 40–90 nM, respectively. Our experiments provide a framework to create a versatile technology platform for the development of ATCs for precise detection and treatment of ovarian cancer cells.
20 citations
TL;DR: A simple and selective bioanalytical method was developed for simultaneous determination of levodopa and carbidopa in rat plasma by LC-MS/MS and was successfully applied to analyze rat plasma samples from in-life studies.
20 citations
TL;DR: RI-002 offers potential advantages over other available IG’s for prophylaxis in immunocompromised patients requiring polyclonal immunoglobulin supplementation because of its unique antibody composition.
Abstract: Introduction: Novel immune globulin (IG) products (RI-002, RI-001) have been designed to provide protection against respiratory syncytial virus (RSV) mediated respiratory illness while at the same time meeting the manufacturing requirements established by FDA for antibody supplementation in immunocompromised subjects.Areas covered: This review covers the manufacture and development of both RI-001 and RI-002, including the selection of plasma donors for IG preparation with high-titers of anti-RSV antibody, in vitro, and preclinical data in the cotton rat model S. hispidus, and clinical trials including Phase II and compassionate use studies of RI-001 and a multi-center, pivotal Phase III study of RI-002 in PIDD patients.Expert commentary: The data demonstrate that RI-002 is efficacious in the prevention and treatment of RSV in preclinical normal and immune suppressed animal models and is safe and efficacious in the treatment of patients with various forms of primary immunodeficiency disease (PIDD)....
18 citations
TL;DR: While overall use of prostacyclins was relatively constant from 2010 to 2015, the findings revealed a shift from parenteral to nonparenteral formulations, coupled with increased prescribing of PAH-related medications from other drug classes.
Abstract: BACKGROUND: Prostacyclins play an important role in the management of pulmonary arterial hypertension (PAH). Intravenous prostacyclin was the first disease-specific treatment for patients with PAH. Subcutaneous and nonparenteral (oral or inhaled) formulations have subsequently become available. However, data are lacking on how these different prostacyclin formulations are being used in clinical practice. OBJECTIVES: To (a) conduct retrospective analyses of a large U.S. health care claims database to describe the characteristics of patients with PAH initiating prostacyclin therapy, and (b) evaluate their treatment patterns, health care resource use, and associated costs. METHODS: Truven Commercial and Medicare databases were used to define annual cohorts of adults with PAH between January 1, 2010, and October 31, 2015. These patients were identified based on claims with ICD-9-CM diagnoses indicative of PAH (codes 416.0 or 416.8) and claims for PAH-specific medications and PAH-related procedures. Patients w...
TL;DR: Albiglutide treatment was associated with higher rates of diarrhoea and injection-site reactions, but not increased nausea and vomiting, versus all comparators, and this analysis of clinical studies of up to 3years evaluated the safety of albig lutide, a GLP-1 RA, in people with T2DM.
TL;DR: Pediatric solid organ transplant recipients have a 100 to 200 times higher risk of non‐Hodgkin lymphoma than the general pediatric population, and transplant‐related NHL may contribute considerably to the pediatric NHL burden in the United States.
Abstract: BACKGROUND
Pediatric solid organ transplant recipients have a 100 to 200 times higher risk of non-Hodgkin lymphoma (NHL) than the general pediatric population. Consequently, transplant-related NHL may contribute considerably to the pediatric NHL burden in the United States.
METHODS
A cohort study using a linkage between the US transplant registry and 16 cancer registries was conducted. Cancer incidence rates were calculated for people less than 20 years old in the transplant and general populations. Rates were applied to transplant registry and US census data to estimate pediatric NHL counts for transplant recipients and the general population.
RESULTS
During 1990-2012, an estimated 22,270 NHLs were diagnosed in US children and adolescents; they included 628 cases diagnosed in transplant recipients. Thus, 2.82% of pediatric NHL diagnoses in the general population (95% confidence interval [CI], 2.45%-3.19%) occurred in transplant recipients. Among transplant recipients, the most common subtypes were diffuse large B-cell lymphoma (DLBCL; 64.5% of cases) and Burkitt lymphoma (BL; 8.6%). For DLBCL and BL, transplant recipients contributed 7.62% (95% CI, 6.35%-8.88%) and 0.87% (95% CI, 0.51%-1.23%) of diagnoses, respectively. The proportion of NHLs that occurred in transplant recipients was highest among children less than 5 years old (4.46%; 95% CI, 3.24%-5.69%) and in more recent calendar years (3.73% in 2010-2012; 95% CI, 2.07%-5.39%). DLBCL patterns were similar, with transplant recipients contributing 19.78% of cases among children less than 5 years old (95% CI, 12.89%-26.66%) and 11.4% of cases in 2010-2012 (95% CI, 5.54%-17.28%).
CONCLUSIONS
Among children and adolescents, solid organ transplant recipients contribute a substantial fraction of NHL diagnoses, particularly DLBCL diagnoses. This fraction has increased over time. Prevention efforts targeted toward this group could reduce the overall pediatric NHL burden. Cancer 2017. © 2017 American Cancer Society.
TL;DR: The anxiety, jointed with the socioeconomic variables and supplemental therapy, is a significant fatigue predictor in RA patients, while accompanied with the basic RA treatment they exclusively explain a high depression.
Abstract: Introduction Fatigue, anxiety and depression are very frequent symptoms in patients with rheumatoid arthritis (RA). Goals In this study we evaluated the influence of socioeconomic characteristics, therapy and comorbidities on the self-reported high fatigue, anxiety and depression in patients with RA. Method Multicenter cross-sectional study was performed in 22 health institutions in Serbia during the period from April–August 2014 in population of older RA patients. Self-reported patients health status was measured by: Fatigue Assessment Scale, Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7. Treatment modalities were defined as: (1) non-steroidal anti-inflammatory drugs (NSAIDs) and/or analgesics and/or corticosteroids; (2) synthetic disease-modifying antirheumatic drugs (DMARDs) alone or in combination with corticosteroids and/or NSAIDs and (3) any RA treatment which includes biologic DMARDs. Results There were significant predictors of high depression: synthetic DMARDs therapy in combination with corticosteroids and/or NSAIDs, physiotherapist self-payment, frequent taxi use, alternative treatment and employment status. The need for another person's assistance, supplemental calcium therapy and professional qualifications were the predictors of a high fatigue, whereas the age above 65 years had the protective effect on it. Anxiety was an independent high fatigue predictor. The predictors of a high anxiety were: gastroprotection with proton-pump inhibitors and patient occupation. Conclusion Socioeconomic predictors of self-reported high depression, anxiety or fatigue are different for each of the mentioned outcomes, while accompanied with the basic RA treatment they exclusively explain a high depression. The anxiety, jointed with the socioeconomic variables and supplemental therapy, is a significant fatigue predictor in RA patients.
TL;DR: The results obtained in this study show that the extracting power of a medium, whether solid or liquid, was primarily a function of polarity and thus could be related to one another.
Abstract: Lyophilization is commonly used to extend the shelf life of pharmaceutical products which are otherwise unstable when stored as a liquid formulation. However, the ability of a lyophilized drug, or other solid medium, to leach or extract substances from a pharmaceutical packaging material is not well characterized. To provide insight into this area of uncertainty, the extraction properties of a lyophilized drug product, the lyophilized drug product reconstituted in water, and several other solid and liquid media of varying polarity were determined using a glass vial with a butyl rubber stopper as a representative pharmaceutical packaging system. The results obtained in this study show that the extracting power of a medium, whether solid or liquid, was primarily a function of polarity. Thus, the amount of each extractable observed for the lyophilized and reconstituted drug product were in-trend with the other solid and liquid media, respectively.
Nevertheless, it was notable that the lyophilized drug product was able to leach substances from the stopper in quantifiable amounts, whereas the reconstituted drug product contained no detectable leachables. Using a mathematical relationship, it was determined that the extraction power of the lyophilized drug product was equivalent to a 50/50 isopropanol/water solution.
TL;DR: This work proposes a Bayesian sequential design for binary outcome using an alpha-spending function to control the overall type I error rate and proposes a new stopping rule for futility.
Abstract: Several researchers have proposed solutions to control type I error rate in sequential designs. The use of Bayesian sequential design becomes more common; however, these designs are subject to inflation of the type I error rate. We propose a Bayesian sequential design for binary outcome using an alpha-spending function to control the overall type I error rate. Algorithms are presented for calculating critical values and power for the proposed designs. We also propose a new stopping rule for futility. Sensitivity analysis is implemented for assessing the effects of varying the parameters of the prior distribution and maximum total sample size on critical values. Alpha-spending functions are compared using power and actual sample size through simulations. Further simulations show that, when total sample size is fixed, the proposed design has greater power than the traditional Bayesian sequential design, which sets equal stopping bounds at all interim analyses. We also find that the proposed design with the new stopping for futility rule results in greater power and can stop earlier with a smaller actual sample size, compared with the traditional stopping rule for futility when all other conditions are held constant. Finally, we apply the proposed method to a real data set and compare the results with traditional designs.
01 May 2017
TL;DR: A tensor boosting algorithm for classification based on neuroimaging data that is off-the-shelf, computationally simple and amenable to various modalities of neuroim imaging data is proposed.
Abstract: Recent advances in medical imaging technologies generate a high volume of imaging data. Classification of cognitive outcome and disease status based on brain images is one of the most important tasks in neuroimaging studies. However it poses great challenge to the current classification methods due to the extremely high dimensionality and low signal to noise ratio in brain image data. In this article we propose a tensor boosting algorithm for classification based on neuroimaging data. The method is off-the-shelf, computationally simple and amenable to various modalities of neuroimaging data. The method is applied to an EEG data set from an alcoholism study and an MRI data set from an ADHD Global Competition and shows significantly improved classification performance.
TL;DR: A simple, rapid and robust site-directed labeling method that can be used to generate homogeneous immunoconjugate with defined pharmacological properties is described.
Abstract: Background Targeted imaging and therapy (theranostics) is a promising approach for the simultaneous improvement of cancer diagnosis, prognosis and management. Therapeutic and imaging reagents are coupled to tumor-targeting molecules such as antibodies, providing a basis for truly personalized medicine. However, the development of antibody-drug conjugates with acceptable pharmaceutical properties is a complex process and several parameters must be optimized, such as the controlled conjugation method and the drug-to-antibody ratio. Objective The major aim of this work is to address fundamental key challenges for the development of versatile technology platform for generating homogenous immunotheranostic reagent. Method We conjugated the theranostics reagent IRDye700dx to a recombinant antibody fusion protein containing a self-labeling protein (SNAP-tag) which provides a unique reaction site. Results The resulting conjugate was suitable for the imaging of cancer cells expressing the epidermal growth factor receptor and demonstrated potent phototherapeutic and imaging activities against them. Conclusion Here, we describe a simple, rapid and robust site-directed labeling method that can be used to generate homogeneous immunoconjugate with defined pharmacological properties.
Ben-Gurion University of the Negev1, University of Nairobi2, University of Washington3, Utrecht University4, University of Maryland Medical Center5, University of Otago6, University of Alberta7, Medical Research Council8, Vanderbilt University9, Vilnius University10, Ministry of Health and Family Welfare11, University of California, San Diego12, World Health Organization13, Pharmaceutical Product Development14, University of Colorado Denver15, Imperial College London16, University of Nigeria, Nsukka17, Novartis18
TL;DR: This estudo transversal multicentrico foi feito em 22 instituicoes de saude na Servia de abril a agosto de 2014 na populacao de pacientes idosos com AR.
Abstract: Resumo Introducao A fadiga, a ansiedade e a depressao sao sintomas muito frequentes em pacientes com artrite reumatoide (AR). Objetivos Neste estudo, avaliou‐se a influencia de caracteristicas socioeconomicas, caracteristicas de tratamento e comorbidades na elevacao na fadiga, ansiedade e depressao autorrelatadas em pacientes com AR. Metodo Este estudo transversal multicentrico foi feito em 22 instituicoes de saude na Servia de abril a agosto de 2014 na populacao de pacientes idosos com AR. O status de saude autorrelatado dos pacientes foi medido pelos instrumentos Fatigue Assessment Scale, Patient Health Questionnaire‐9 e Generalized Anxiety Disorder‐7. As modalidades de tratamento foram definidas como: 1) anti‐inflamatorios nao esteroides (AINE) e/ou analgesicos e/ou corticosteroides; 2) farmacos antirreumaticos modificadores da doenca sinteticos (DMARD) isoladamente ou em combinacao com corticosteroides e/ou AINE e 3) qualquer tratamento para a AR que incluisse DMARD biologicos. Resultados Houve preditores significativos de depressao elevada: tratamento com DMARD sinteticos em combinacao com corticosteroides e/ou AINE, pagamento particular de fisioterapia, uso frequente de servicos de taxi, terapias alternativas e status ocupacional. A necessidade de assistencia de outra pessoa, o tratamento suplementar com calcio e as qualificacoes profissionais foram os preditores de fadiga elevada. A idade acima de 65 anos teve um efeito protetor sobre a fadiga elevada. A ansiedade foi um preditor independente de fadiga elevada. Os preditores ansiedade elevada foram: gastroprotecao com inibidores da bomba de protons e ocupacao do paciente. Conclusao Os preditores socioeconomicos de niveis elevados de depressao, ansiedade ou fadiga autorrelatadas sao diferentes para cada um dos desfechos mencionados; quando acompanhados do tratamento basico para a AR, esses preditores socioeconomicos explicam exclusivamente uma depressao elevada. A ansiedade, associada as variaveis socioeconomicas e ao tratamento complementar, e um importante preditor da fadiga em pacientes com AR.
TL;DR: First evidence that SNAP-tag could be used for ex vivo detection of enriched biological markers is reported, in comparison with anti-c-kit antibody for peripheral blood samples from leukemia patients and colorectal tissue specimens.
Abstract: SNAP-tag, a self-labeling protein tag, is commonly used for in vitro and in vivo analysis of bound target proteins. We report the first evidence that SNAP-tag could be used for ex vivo detection of enriched biological markers. Proof of concept was established for target c-kit receptor, a pathological and diagnostic marker for a variety of cancers. SNAP-tag conjugates with stem-cell factor (SCF) fusion proteins were designed and their binding and specificity was validated in vitro using flow cytometry and immunostaining. Ex vivo diagnostic application of the fusion protein was demonstrated in comparison with anti-c-kit antibody for peripheral blood samples from leukemia patients and colorectal tissue specimens.
TL;DR: This paper proposes a Bayesian sequential design with adaptive randomization rates so as to more efficiently attribute newly recruited patients to different treatment arms in 2-arm clinical trials.
Abstract: Bayesian sequential and adaptive randomization designs are gaining popularity in clinical trials thanks to their potentials to reduce the number of required participants and save resources. We propose a Bayesian sequential design with adaptive randomization rates so as to more efficiently attribute newly recruited patients to different treatment arms. In this paper, we consider 2-arm clinical trials. Patients are allocated to the 2 arms with a randomization rate to achieve minimum variance for the test statistic. Algorithms are presented to calculate the optimal randomization rate, critical values, and power for the proposed design. Sensitivity analysis is implemented to check the influence on design by changing the prior distributions. Simulation studies are applied to compare the proposed method and traditional methods in terms of power and actual sample sizes. Simulations show that, when total sample size is fixed, the proposed design can obtain greater power and/or cost smaller actual sample size than the traditional Bayesian sequential design. Finally, we apply the proposed method to a real data set and compare the results with the Bayesian sequential design without adaptive randomization in terms of sample sizes. The proposed method can further reduce required sample size.
01 Jan 2017
TL;DR: What is currently known regarding biomarkers for rheumatoid arthritis is explored and issues to be addressed are discussed as biomarkers are sought for future development programs.
Abstract: Rheumatoid arthritis is a complex systemic autoimmune disease that is characterized by chronic inflammatory polyarthritis, extra-articular features, and autoantibody formation. Although a targeted therapeutic approach using disease-modifying rheumatic drugs has markedly improved overall patient outcomes, there remain significant delays in accomplishing low disease activity in many patients. Reducing the numbers of patients needed for clinical trials is essential to the future of rheumatoid arthritis medical product development programs. Integration of biomarkers into clinical trials for rheumatoid arthritis may be helpful for early disease detection, patient stratification, and treatment response assessment. This goal has not yet been realized but can be achievable with good basic and applied research, systematic data collection, and data systems that can be used to integrate and share data. Herein, we explore what is currently known regarding biomarkers for rheumatoid arthritis and discuss issues to be addressed as biomarkers are sought for future development programs.
01 May 2017
TL;DR: A Bayesian solution for dimension reduction which incorporates group knowledge in terms of the sufficient predictors using a finite mixture model and is computationally efficient and offers a unified framework to handle categorical predictor, missing predictors, and Bayesian variable selection.
Abstract: Nearly all existing estimations of the central subspace in regression take the frequentist approach. However, when the predictors fall naturally into a number of groups, these frequentist methods treat all predictors indiscriminately and can result in loss of the group-specific relation between the response and the predictors. In this article, we propose a Bayesian solution for dimension reduction which incorporates such group knowledge. We place a prior whose variance is constrained to the form of a direct sum on the central subspace and directly model the response density in terms of the sufficient predictors using a finite mixture model. This approach is computationally efficient and offers a unified framework to handle categorical predictors, missing predictors, and Bayesian variable selection. We illustrate the method using both a simulation study and an analysis of a temperature data set.