An Emerging Threat for Therapeutic Drug Development
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comment Corrected: Author Correction ‘Stealth’ corporate innovation: an emerging threat for therapeutic drug development Therapeutic innovations of potentially great clinical impact should embrace the overarching values of research accountability, data transparency and validation through the scientifc peer-review process. Dimitrios C. Mastellos, Anna M. Blom, E. Sander Connolly, Mohamed R. Daha, Brian V. Geisbrecht, Berhane Ghebrehiwet, Piet Gros, George Hajishengallis, V. Michael Holers, Markus Huber-Lang, Taroh Kinoshita, Tom E. Mollnes, Robert A. Montgomery, B. Paul Morgan, Bo Nilsson, Ruben Pio, Daniel Ricklin, Antonio M. Risitano, Ronald P. Taylor, Alberto Mantovani, John P. A. Ioannidis and John D. Lambris “It is terrible to become rich and to know publications. Taxpayers and donors should evaluation of its validity and the long-term nothing else.”—Euripides know that their hard-earned contributions consequences of its conclusions. are being invested in work that gets validated The exposure of some types of industrial Academic research and industrial by rigorous peer review and also may research results to rigorous peer review innovation are both integral drivers of eventually help patients. Such opportunities is lagging behind that of their academic the discovery process that eventually can be nourished only by robust scientific counterparts. This insufficient peer culminates in innovative therapies and new evidence and peer-validated technologies validation may be a more prominent issue medicines1. Academic research is conducted in the development of innovative patient for research covering the early stages on university, hospital or research-center treatments2. Naturally, similar requirements of the discovery–to–clinical validation campuses furnished with several degrees for transparency and data integrity should pipeline, which is usually conducted by of freedom but also hampered by funding also apply when such research is partially smaller companies (including start-ups) constraints. Industrial research in large or fully conducted by start-ups, regardless than for larger biopharma companies companies tends to resonate more with the of which investigators are involved (e.g., working further down the pipeline. The rigid organizational blueprint and internal from academic institutions, hospitals and/ lack of peer-reviewed publications from regulatory control that spans the entire or companies). small companies and start-ups has been spectrum of corporate structure. Start-up Rigorous scientific scrutiny at all attributed to many factors, among which the companies (start-ups) are somewhere in the steps of the discovery process is essential protection of corporate intellectual property middle: they may have components of both regardless of whether this innovation is from competition holds a prominent place, academic and industrial origin, but in theory generated in university laboratories or especially for early-stage research3. Most their major advantage is that they can avoid in cubicles at biotechnology (biotech) major pharmaceutical companies engage in both the funding constraints of academia companies. The introduction of therapeutic peer review of their technologies or products and the rigid organizational constraints of innovations of potentially great clinical at critical checkpoints of technology large companies. impact carries even greater responsibility development. However, it is the aspiring Academically led innovation typically for communicating and engaging with the start-ups and small- or medium-sized thrives on competitive funding from public scientific community through clear and biotech enterprises that tend to rely more agencies and charities, and this makes the demonstrably consistent underpinning on media exposure than on actual scientific investment of a comparatively large portion data. Data validation by means of peer- evidence, in an effort to direct investor of such funding on high-risk ideas difficult. reviewed publications should also apply to funding toward their products, as early as Large companies are also increasingly risk- medicinal products discovered and clinically possible4. This evolving and increasingly averse in trying to invest in innovation and developed entirely within industrial accepted practice of shielding scientifically leave much of this early, high-failure-rate venues. The investor-driven funding that important corporate data is at odds with the step to start-ups or academic laboratories. enables start-up and biopharmaceutical standards of research accountability through The reliance of academic research (biopharma) research to advance its pipeline peer evaluation, data transparency, research on public funding mandates a strong of products through clinical development integrity and data openness5. sense of accountability, mainly toward should not create impediments to the Placing such general considerations the contributing taxpayers or charity maintenance of data transparency and into perspective, Cristea and colleagues donors (i.e., the broader public). In turn, open access to research. Industry-based evaluated the lack of peer-reviewed this research accountability should be research should not be communicated evidence from healthcare ‘unicorns’6 — reflected in a high level of data integrity only among company executives, investors, that is, biotech start-ups with promising and transparency, which is achieved mainly stockbrokers or venture capitalists through technologies and market valuations that through several rounds of review by expert vaguely formulated press releases with no exceed the US$1 billion threshold. Many scientists before the described research primary data or independently validated start-ups had secured exceedingly high product (e.g., drug target or candidate) can conclusions. Instead, its underpinning data market valuations despite a lack of peer- reach the public domain in peer-reviewed should be made publicly available to allow reviewed publications to support their NATURE IMMUNOLOGY | VOL 20 | NOVEMBER 2019 | 1409–1413 | www.nature.com/natureimmunology 1409 comment Market value vs. peer-reviewed research output market valuations that probably reflect 12 2 mounting investor interest in what appears 2009 2007 * to be a rapidly evolving field of not only 1.8 clinical opportunity but also commercial 10 opportunity. But is this interest of the capital 2008 2013 1.6 * market firmly rooted in scientific facts or is Market cap (billions in US$) 1.4 it driven instead by media hype? 8 To gain insight into the extent to 1.2 which complement-dedicated start- 1997 ups with high market valuations have 6 1 1994 engaged in peer-review validation of Publications 1997 0.8 their products, we conducted a literature 2011 4 1998 2007 search for publications co-authored by 0.6 1996 2004 these companies. Scopus (Elsevier) was 1999 selected as our literature search engine, 1994 2004 0.4 2 and our retrievals included original 0.2 research articles, editorials and reviews. The ‘affiliation name’ of the company 2014 2010 0 0 was combined in a search for documents s h a e N s n E x a Ra c s cs s a s ti Akaritic ces one that included the term ‘complement’ in Apellis InflaRx ilen ls Omero S OXXO A Hemer Achillion AmyndaAnnexo N Pharm scien ADIENN the title, abstract and/or keywords and Ophthotec io ChemoCentryxInnate PharmTherapeuTherapeu B Bioscience Zealand Pharma also in extracted metadata (all fields) PharmaceuticalPharmaceuticals Publications Market cap (billions) associated with the document in question. All publications were cross-validated Fig. 1 | Market valuation of complement-related drug–development companies versus research output manually for the true association of their (peer-reviewed publications of company-sponsored research) that validates their complement- content (abstract) to complement research related technology or drug candidate. All market caps were retrieved through Yahoo’s finance search or complement-targeting therapeutics, with engine (https://finance.yahoo.com/) and were converted for uniformity into US currency (right vertical exclusion of use of the term ‘complement’ in axis) on the basis of currency exchange rates as of 30 July 2019. Our analysis included five privately held its grammatical sense. We chose to include companies (not listed on the stock exchange): ADIENNE, Alsonex, Amyndas, Annexon Biosciences and in our analysis 17 companies with clinical- Hemera Biosciences. For reasons of conformity, market values for these companies are shown as US$0 stage complement drug leads disclosed here. ‘Publications’ (left vertical axis) refers to peer-reviewed papers (original research articles, reviews through their official websites, focusing and editorials) retrieved through Elsevier’s Scopus search engine (https://www.elsevier.com/solutions/ on programs whose documentation in the scopus). Conference presentations, conference proceedings or corporate presentations and investor- literature commenced since 2003 and on and/or shareholder-oriented releases have been excluded from this analysis. All the primary data used complement innovators with consistent 9 for this analysis, with details on each company’s publication record and related citations, are provided commitment to this drug space . We in Supplementary Datasets 1 and 2. Numbers above bars indicate the year in which each company was focused only on start-ups; thus, large founded; asterisks indicate companies that are clinically developing different versions of the same C3- global healthcare