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Taking phototherapeutics from concept to clinical launch.

ABSTRACT: More than four decades have passed since the first example of a light-activated (caged) compound was described. In the intervening years, a large number of light-responsive derivatives have been reported, several of which have found utility under a variety of in vitro conditions using cells and tissues. Light-triggered bioactivity furnishes spatial and temporal control, and offers the possibility of precision dosing and orthogonal communication with different biomolecules. These inherent attributes of light have been advocated as advantageous for the delivery and/or activation of drugs at diseased sites for a variety of indications. However, the tissue penetrance of light is profoundly wavelength-dependent. Only recently have phototherapeutics that are photoresponsive in the optical window of tissue (600-900 nm) been described. This Review highlights these recent discoveries, along with their limitations and clinical opportunities. In addition, we describe preliminary in vivo studies of prospective phototherapeutics, with an emphasis on the path that remains to be navigated in order to translate light-activated drugs into clinically useful therapeutics. Finally, the unique attributes of phototherapeutics is highlighted by discussing several potential disease applications.

SUBMITTER: Vickerman BM

PROVIDER: S-EPMC8493544 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Taking phototherapeutics from concept to clinical launch.

Vickerman Brianna M BM Zywot Emilia M EM Tarrant Teresa K TK Lawrence David S DS

Nature reviews. Chemistry 20211006 11

More than four decades have passed since the first example of a light-activated (caged) compound was described. In the intervening years, a large number of light-responsive derivatives have been reported, several of which have found utility under a variety of in vitro conditions using cells and tissues. Light-triggered bioactivity furnishes spatial and temporal control, and offers the possibility of precision dosing and orthogonal communication with different biomolecules. These inherent attribu ...[more]

PMID: 37117665

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Project description:BackgroundRising cancer drug prices adversely affect patients' adherence and survival.ObjectiveWe aimed to identify and quantify factors associated with launch prices and post-launch price changes of injectable cancer drugs in the US from 2005 to 2023.Data and methodsAll anticancer drugs with US FDA approval between 2000 and 2022 were identified in the Drugs@FDA database. The sample was then restricted to cancer drugs covered under Medicare Part B (injectable drugs). Data characterizing each drug's clinical benefits, disease epidemiology, approved indications, competition, and price were obtained from FDA labels, the Global Burden of Disease study, and the Centers for Medicare and Medicaid Services. The association between launch/post-launch prices and collected variables was assessed in random-effects regressions.ResultsOf 170 cancer drugs with FDA approval between 2000 and 2022, we identified 66 (39%) injectable cancer drugs with quarterly price data from 2005 to 2023. In 2023, mean prices amounted to $27,688 per month, with an average price increase of 94% from 2005 to 2023. Launch and post-launch price changes were significantly associated with the treated disease epidemiology. A 1% decline in disease incidence was associated with a 0.2511% (p = 0.008) increase in launch prices and a 0.0086% (p = 0.032) annual increase in post-launch prices. Accordingly, launch prices were 120% (p = 0.051) higher for orphan than non-orphan drugs, with 3% (p = 0.008) greater annual post-launch price increases. Post-launch prices declined by up to -2% annually as new supplemental indications were approved for the same drug. We found no consistent association between launch/post-launch prices and the drugs' clinical benefit in terms of overall survival, progression-free survival, and tumor response. The market entry of new competitors was not associated with price reductions. 28 of 33 drug pairs within the same class had positive correlation coefficients. Pearson correlation coefficients were high (>0.80) for PD-1/PD-L1 inhibitors, CD38 antibodies, CD20 antibodies, HER2 antibodies, and mTOR inhibitors.ConclusionsCancer drug prices regularly increase faster than inflation; however, there is no evidence that launch prices and post-launch price changes are aligned with the clinical benefit a drug offers to patients. In particular, patients with rare diseases experience greater price increases for their orphan drugs. There is no evidence that brand-brand competition results in drug price reductions.

Project description:ImportanceThe high cost of cancer medicines is a public health challenge. Policy makers in the US and Europe are debating reforms to drug pricing that would cover both the prices of new medicines when entering the market and price increases after they are launched.ObjectiveTo assess launch prices, postlaunch price changes, and clinical benefit of cancer drugs in the US compared with 3 European countries (England, Germany, and Switzerland).Design, setting, and participantsThis economic evaluation identified all new drugs that were approved for use in the US, England, Germany, and Switzerland with initial indications for treatment of adult solid tumor and hematologic cancers. Analysis included drugs approved by the US Food and Drug Administration between January 1, 2009, and December 31, 2019, and by the European Medicines Agency and Swissmedic until December 31, 2019. Prices were adjusted for currency and inflation. Clinical benefit of drugs indicated for solid tumors was assessed using the American Society of Clinical Oncology Value Framework and European Society for Medical Oncology Magnitude of Clinical Benefit Scale. Using Spearman rank correlation coefficients, correlations between clinical benefit and launch prices and postlaunch price changes for each country were evaluated.Main outcomes and measuresLaunch prices, postlaunch price changes, and clinical benefit of cancer drugs.ResultsThe cohort included 65 drugs: 47 (72%) approved for solid tumors and 18 (28%) for hematologic cancers. In all countries, the lowest median monthly treatment costs at launch were greater in 2018-2019 vs 2009-2010: $14 580 vs $5790 in the US, $5888 vs $4289 in Germany, $6593 vs $5784 in Switzerland, and $6867 vs $3939 in England. Between 2009 and 2019, 48 of 65 (74%) cancer drugs had price increases in the US that were greater than inflation. Only 1 of 62 (2%) drugs in England, 0 of 60 drugs in Germany, and 7 of 56 drugs (13%) in Switzerland had a median price increase greater than inflation. There were no associations between launch prices or postlaunch price changes and clinical benefit in any assessed country.Conclusions and relevanceDuring this economic evaluation study period, launch prices of cancer drugs were substantially higher in the US than in the assessed similar high-income European countries, a gap that increased in the years after approval. Cancer drug prices frequently increased faster than inflation in the US but decreased on inflation-adjusted terms in Europe. Price changes were not associated with clinical benefit in any country.

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Taking phototherapeutics from concept to clinical launch.

Publications

Taking phototherapeutics from concept to clinical launch.

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