WEEK OF MARCH 31, 2014 BioCentury THE BERNSTEIN REPORT ON BIOBUSINESS Volume 22 • Number 13 • Page A1 of 23 Regulation Viral crossroads By Steve Usdin BioCentury This Week Washington Editor Now that the family of seven-year-old Cover Story platform produces synthetic peptides with Josh Hardy has successfully obtained ac- the binding specificity and affinity of mAbs cess to an experimental drug, aided by an Viral crossroads — The Josh Hardy and many of the biological properties of explosion of social media support, law- case highlights the inadequacy of the small molecules./A13 makers, industry and patients still are left process for deciding when to grant access grappling with the fundamental inequities to experimental medicines outside of Finance and flaws of the U.S. system for granting clinical trials. It also may be a catalyst for compassionate access to investigational change. Steady Hand — LSP has survived 25 years as therapies. Josh Hardy Chronicles — While social a life sciences VC by making a few small changes The problems have existed for years, media users may be claiming the credit, in to an otherwise single-minded strategy fo- including the idiosyncrasies of who gets the end Chimerix and FDA had to clear a cused on investing in early stage European access to investigational drugs outside of way to provide brincidofovir to a handful biotechs./A14 clinical trials and the criteria companies of patients while opening a door for Ebb & Flow — Biotech slip-sliding away? use to make decisions that are often life- broader access via a bigger trial./A7 Endocyte tops up. Ysios’ new fund. and-death. Commentary: The Equitable Pathway NetScientific-Breakout Labs. Also: Epigenomics; The fact that individual companies have — It is possible to identify basic principles Exact Sciences; MannKind; Cellectis; Exelixis; been left to make these decisions on an ad that should underlie a transparent system Idera; Horizon Discovery; Zogenix, et al./A17 hoc basis inevitably fuels suspicions among for reviewing compassionate use requests, patients, family members and the public no matter who does the assessment./A9 Featured links this week/A21 about the motives for denying access. The difference in perspectives between Stock charts & tables/A22 companies focused on gaining regulatory Emerging Company Profile Company index/A16 approval and individuals trying to save Going Small — ImmuSmol’s antibodies desperately ill loved ones can make mutual suspicion curdle into antagonism. treat cancer by targeting small molecule TM BioCentury 100 Indicators metabolites involved in tumor immune See next page evasion./A12 Week ended 3/28/14 Building Better Binders — Indi PRICES VOLUME Molecular’s protein-catalyzed capture 4983.60 1113.7M shrs dn 8% up 11% FUELING THE FIRE Wall Street, ACA & Prices Tokyo Calling www.biocenturytv.com BIO Asia is less than two weeks away but there’s still time to register for this exclusive partnering forum. Details follow A23. 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BioCentury, THE BERNSTEIN REPORT ON BIOBUSINESS MARCH 31, 2014 PAGE A2 OF 23 Regulation, The guidance lists criteria FDA applies from previous page “I worry — are cases like to review expanded access applications, including a determination that the “poten- The rise of social media as an advocacy Josh’s going to set a tial benefit justifies the potential risks of tool now raises the prospect that medical new standard for how the treatment use with the drug and that and regulatory decisions will be tipped by those risks are not unreasonable in the a public outcry. patients pursue this?” context of the disease or condition to be As the Hardy case illustrates, patients treated.” or their relatives can generate hundreds of Richard Klein, FDA FDA must determine that providing thousands of supporters virtually over- expanded access “will not interfere with night, along with a wave of attention on FDA procedures development of the drug for the expanded television. In the heat of a media feeding access use, and that the patient cannot frenzy, it is impossible for a CEO to The medical, ethical, business and lo- gistical aspects of providing access to obtain the drug under another IND or communicate the complexities of drug protocol.” development and why the integrity of the investigational drugs can be complex and To reduce impediments to expanded regulatory approval pathway must be pro- contentious, but the regulatory pathway is straightforward. access, FDA does not require reporting of tected to get a drug to as many patients as outcomes data. possible. While companies, patients and the “Expanded access is designed for regu- And a CEO who says “no” is no match media sometimes accuse FDA of prevent- ing compassionate access to an investiga- lar doctors — treating physicians as op- for 100,000 angry Twitter messages and posed to research doctors — so reporting death threats from angry individuals who tional drug, data show the agency virtually requirements are minimized,” Klein told jump on the bandwagon. The threat of never denies requests. This does not mean patients always get BioCentury. FDA requires reports only demonization has led companies to be about basic safety information, such as wary of individuals and groups seeking to access to unapproved drugs. Requests for “serious and unexpected adverse events obtain compassionate use access to their access must be submitted by drug spon- sors or with their permission. Patients that may be related to the drug, for ex- products. ample liver failure,” he added. While the Hardy case reflects old prob- cannot apply directly to FDA, and the As a result, Klein noted, FDA only has lems, it also may be a game-changer. The agency will not process an application from a physician unless a sponsor is anecdotal information about the efficacy almost immediate and apparently extraor- of drugs provided under expanded ac- dinary effectiveness of Chimerix Inc.’s willing to provide access to its product. That does not mean FDA always cess. brincidofovir for Josh Hardy, coupled with In some cases, as with Chimerix’s the power of social media to push the plays a passive role. Agency officials brincidofovir, the agency works with com- company to find a way to provide access, sometimes reach out to companies to encourage them to provide access to panies to create a clinical trial that could have already led other families to pursue lead to a new approval or expanded indi- similar campaigns (see “The Josh Hardy investigational drugs, according to Ri- cation. Chronicles,” A7). chard Klein, director of FDA’s Patient Liaison Program. But while Josh Hardy’s response to The Hardy case also has prompted brincidofovir may have been dramatic, members of Congress, industry trade as- The agency has initiated expanded Klein noted the feedback FDA receives sociations, patient advocacy groups and access discussions with companies based on requests from patients, media coverage suggests that patients and physicians seek- individual companies to reassess the need ing expanded access are often over-confi- for new principles to guide compassionate and other triggers. dent about the potential for experimental access decision-making in the era of social Biotech executives report they’ve re- ceived calls from FDA relaying requests treatments to provide dramatic cures. media and patient empowerment. “Every now and then people will call Biotech industry leaders are suggest- from members of Congress for family mem- back and say, ‘We really appreciate the ing it may be time to shift some decisions bers or constituents to receive access to investigational drugs. help, but my mom has died’,” he said. “No about compassionate access off the shoul- one has ever called up and said, ‘I really ders of CEOs and onto new institutions to FDA has used the term “compassion- appreciate the help, and my mom’s great.’ help adjudicate requests for pre-approval ate access” in the past, but now it uses “expanded access to investigational drugs You would think they would be more access to medicines. likely to call if that happened.” All of this points to the need for public for treatment use.” According to guidance There are, however, numerous reports consensus on a transparent pathway for released in 2013, expanded access is in- tended “for patients with serious or imme- in the medical literature of positive re- making decisions about compassionate sponses to compassionate use treatments. access (see “Commentary,” A9 & “Decision diately life-threatening diseases or condi- For example, in 2009 German researchers Tree for Compassionate Use,” A11). tions who lack therapeutic alternatives.” reported in Blood that compassionate use of Nexavar sorafenib in five patients with acute myelogenous leukemia (AML) pro- duced “sustained regression before and This Week in SciBX after allogeneic stem cell transplantation.” And the first published report about Bitter Taste for Sinus Infections — A Penn study has shown that bitter taste agonists the efficacy of brincidofovir recounted the stimulate release of antimicrobial peptides in the sinuses, suggesting a new way to treat dramatic rescue of a pediatric transplant chronic rhinosinusitis. SciBX Table of Contents, A15. See next page BioCentury, THE