WEEK OF APRIL 21, 2014 BioCentury THE BERNSTEIN REPORT ON BIOBUSINESS Volume 22 • Number 16 • Page A1 of 19 Politics, Policy & Law ASCO’s honest broker By Steve Usdin BioCentury This Week Washington Editor A new access program and registry Cover Story Regulation developed by the American Society of Clinical Oncology to facilitate use of off- Honest Brokers — ASCO is developing Pain Politics — FDA Commissioner Mar- label cancer drugs could serve as a model an initiative to facilitate off-label access to garet Hamburg responds to critics of the for independent bodies that could manage targeted cancer therapies. If successful, the agency’s decision to approve Zogenix’s early access to experimental therapies, even system could serve as a model for third- Zohydro and warns about consequences though ASCO itself is not tackling compas- party bodies that could manage early for the integrity of science-based regula- sionate use. access to experimental therapies. tion./A10 ASCO’s initiative is designed to match off-label targeted cancer therapies to indi- Product Discovery & Development Finance vidual patients likely to benefit based on the genomic profile of their tumors, while col- CAR Hits Pothole — Adverse events led Ebb & Flow — Double-dippers defer lecting data about new uses for approved to protocol revisions in Sloan Kettering’s follow-on plans. Snake eyes for Cytos. drugs. trial of CD19-targeted CAR T cells. But Kaleo’s royalty deal. Epirus makes it move. “We should develop programs to make partner Juno Therapeutics and other CAR Steve Harr’s jump to Juno. Also: ALK- it easier to access drugs, but require more players don’t think this indicates a class Abello; Medivir; ThromboGenics; detailed reporting of outcomes, which is just effect./A5 Topotarget; Zogenix, et al./A12 the opposite of the current situation,” CMO Richard Schilsky told BioCentury. “Doing Emerging Company Profile Featured links this week/A11 so would provide treatment options to pa- Stock charts & tables/A19 tients in need and allow us to learn from all Mediating Rare Metabolism — Minoryx these patient experiences.” Company index/A7 both identifies novel chaperones and Like programs that grant early access to repurposes drugs to treat inherited metabolic experimental medicine, or compassionate diseases./A8 access, ASCO plans to limit its off-label Dynamiting Complement — True North’s initiative to patients who are not eligible for TM TNT009 inhibits an upstream target in the BioCentury 100 Indicators See next page classical complement pathway that could lead Week ended 4/18/14 to greater efficacy and an improved safety PRICES VOLUME profile relative to other complement inhibi- 4734.53 772.6M shrs tors./A9 up 1% dn 32% FDA’S PAIN One Month to Amsterdam Hamburg Talks Zohydro The 15th Bio€quity Europe is almost here, featuring the 7th annual BioCentury-Ernst & Young face-off. www.biocenturytv.com See the agenda following A19. See Program Notes on A5 rEVOLUTION Coming New York Calling Only two weeks until the rEVOLUTION Join the 21st meeting of NewsMakers in the Biotech Industry in New York. Symposium kicks off in Boston. Call for Presenting Companies on A13. See announcement following A19. BioCentury, THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 21, 2014 PAGE A2 OF 19 Politics, Policy & Law, sion, that decision has to be made according from previous page “We should develop pro- to prespecified guidelines,” he said. “It has grams to make it easier to to be transparent, and as objective as pos- trials and who have no alternatives. sible — and people have to understand A central feature of the program is the access drugs, but require going in there will be some cases that will be establishment of an honest broker to make more detailed reporting of rejected.” decisions about the allocation of targeted therapies and to collect and analyze out- outcomes, which is just Support needed comes data. the opposite of the If the project is successful for off-label Drug companies will be asked to supply therapies, it could inspire similar schemes current situation.” off-label drugs at no cost, and insurance based on honest brokers affiliated with companies will be asked to pay for all other medical specialty societies that would serve Richard Schilsky, ASCO treatment expenses, Schilsky said. In return, as intermediaries between drug companies drug companies and payers would benefit and patients seeking early access to exper- even for experts,” he added. from the generation of data about off-label imental medicines. Physicians would submit a genomic pro- uses. PhRMA, BIO and their member com- file of a patient’s tumor from a CLIA-certified Schilsky has approached six pharma- panies, as well as patient organizations and lab, along with a proposed treatment plan ceutical companies to discuss the project. congressional staff, are all engaged in sepa- and request for off-label use of a targeted “All have expressed interest in the idea. rate discussions — primarily behind closed therapy, to an honest broker. The dosing None said they are definitely in,” he said. doors — about creating new policies to and regimen would be consistent with label- “No one has said no.” facilitate equitable early access to experi- ing for approved indications. Schilsky said he also has presented the mental therapies. To facilitate such requests, ASCO is concept to “a couple of insurance compa- As BioCentury proposed in a March 31 considering establishing an Internet-based nies. The general response has been: ‘We Commentary, the creation of independent “tumor board” of clinical oncologists and are OK paying for the healthcare costs as third parties is one of several options under molecular pathologists that would review long as we don’t have to pay for the expen- consideration. genomic test results and provide advice to sive drugs.’” To be successful, early access policies physicians, including potential treatment Schilsky also has discussed the concept will have to be aligned with several social options. with senior FDA officials. and scientific trends: social media-fueled The honest broker would review the “FDA feels that if something like this was patient empowerment; the development of application. For approved applications, the set up, it would enhance their understand- highly effective targeted therapies made honest broker would arrange for shipment ing of how these drugs are being used. FDA possible by the integration of molecular of a three-month supply of the drug. The may turn out to be a champion of this kind diagnostics into drug development and clin- patient’s response would be evaluated and, of approach,” he said. ical practice; and a “right to try” movement if appropriate, additional supplies would be Schilsky said ASCO hasn’t determined that is gaining traction among state and dispensed. how much the project will cost or how federal lawmakers. Schilsky said he is “writing a clinical much demand there will be. protocol for what will essentially be an “We plan to start this as a pilot project observational study.” with a limited number of physician practices Access and registry The protocol will be “for patients who scattered around the country, with as many According to Schilsky, ASCO’s program have exhausted all treatment options, but who drugs as we can get into the program was prompted by the realization that many have reasonable performance status, so they initially,” he said. “We want to see if this is oncologists lack the expertise required to have a meaningful chance of benefiting from feasible, if we can we get the drugs to make treatment decisions based on genomic therapy if benefit can be derived.” patients in a reasonable period of time, if test results, as well as the difficulty patients In addition to validating treatment plans, there are any significant patient benefits face in getting reimbursement for off-label the honest broker would maintain a registry from the approach, and if can we get the prescriptions. with information about patient characteris- necessary data from doctors.” “I’m reacting to the rapid penetration of tics and outcomes. ASCO hopes to get the pilot running genetic profiling in the cancer patient pop- ASCO is speaking with several for- and before year end. ulation, with many comprehensive cancer not-for profit entities that could serve as the centers, community hospitals, and commer- honest broker, Schilsky said. cial labs setting up to do multiplex testing,” He noted that clarity about the rules will Pivot point Schilsky said. Interpreting tests results to be key to making an honest broker accept- In a paper describing the program in determine whether a specific genomic vari- able to patients and the public. Nature Reviews Clinical Oncology this month, ant is clinically actionable is “challenging “Any time a third party makes a deci- Schilsky mentioned the possibility of includ- ing investigational drugs. But he told Bio- Century ASCO has decided to stick with approved drugs. This Week in SciBX “It was a question of not biting off more than I could chew. Once you get into Contaminating Cancer Genomes — Two European teams have pinpointed a DNA- investigational drugs, you get into a higher protective enzyme as a chemically tractable target whose inhibition kills cancer cells by level of complexity regarding human sub- accelerating DNA damage. SciBX Table of Contents, A3. See next page BioCentury, THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 21, 2014 PAGE A3 OF 19 Politics, Policy & Law, from previous page ject participation and regulatory oversight,” he said. “There are at least 25 marketed targeted anticancer treatments SciBX This Week that hit 15 or so different genetic targets,” Schilsky added. “We already have a good starting point of the universe of marketed drugs ANALYSIS without having to get into investigational drugs.” ASCO’s project is inspired in part by the growing sophistication COVER STORY of patients who read Contaminating cancer genomes about targeted ther- Two European teams have pinpointed a DNA-protective apies on the Internet “Science is changing, enzyme as a chemically tractable target whose inhibition and request access kills cancer cells by accelerating DNA damage.