Saturday, January 30, 2010

Heidi, et al.: I have summarized the conversation with the VP's and representatives from the pharmaceutical / biotechnology industries regarding incentives promoting greater participation by industry in our public health emergency medical countermeasure enterprise. Where possible, I identify follow-on actions that derive directly from the conversation. There are still important conversations to continue with our commercial partners. Please feel free to modify or add information or perspectives that I did not adequately capture. Also, I did not quote by name the discussions offered by our industrial partners. Best regards George George W. Korch Jr. Senior Science Advisor Assistant Secretary for Preparedness and Response Department of Health & Human Services Summary of meeting with VP’s of pharmaceutical and biotechnology companies 29 January 2010 Eisenhower Executive Office Building Dr. Zeke Emanuel opened the meeting with a problem definition statement that we as a nation need medical countermeasures for public health emergency events ranging from biodefense to emerging infectious diseases, but after years of investment, we still have not been successful in meeting these needs. He indicated that to a certain degree, there is a sense that the big pharmaceutical companies have opted out of assisting in this endeavor, and while there are smaller, biotechnology companies attempting to fill the gap, they lack the experience to complete the task. Ms. Heidi Avery added that this was not to single out big pharma, but that the USG recognizes that it may not have created the best conditions for being a good partner as well. She pointed out that the industry itself has recently struggled with producing approved medical products for more highly valued commercial products. The bottom line is that the President is seriously committed to this problem and this was highlighted in his State of the Union message. This meeting was being held therefore to start a dialogue with industrial partners (big pharma and the biotechnology sector) to gain their perspectives on what government actions can we take to lower the barrier to entry and to increase the attractiveness of partnership, because without big pharma specifically, the whole thing will not work. We need to hear their ideas. Merck started by reminding folks that they had in fact bid on the contract award for the cell culture derived smallpox vaccine, but had not been successful. Merck then indicated that there are three areas of concern that must be addressed to attract companies like theirs to the program: 1. Need to assure an adequate market 2. Need to make the regulatory path much more viable 3. Need to reduce legal liabilities (e.g. tort claims) Markets On the issue of adequate markets, this allows both big pharma and the biotechnology companies to gauge issues on such things as return on investment, infrastructure and operations costs, etc. Even if the market is destined just to be standard replacement of a strategic stockpile, that constitutes a defined market need. NKT Therapeutics, representing the biotechnology sector indicated that ability to define an adequate market is a key variable for their ability as a small company to secure investment funding. (Note: I interpret the relative order of these three items to actually be in a sort of priority order for big pharma). An issue that was cited as an example for how markets might be improved for these products was the use of the Priority Review Voucher System applied to biodefense products as is now afforded to industry for orphan products under the Orphan Drug Act. If a system could be developed wherein the voucher was transferable or saleable to another industry partner, it would represent a value proposition that could be understood by the investor community as a potential opportunity for return on investment. There was discussion regarding the theoretical vs. practical aspect of this advantage for priority review, but agreement that another feature regarding 3 months of granted exclusivity on review would be of value. Regulatory Approval Pathway On the issue of better defining the pathway to regulatory approval of the product, a general description of the preferred process is that the FDA should be very specific in the requirements that a company is expected to demonstrate for a candidate study, rather than the current system where a company provides data for a study, and is then told whether it meets the reviewers’ approval. Dr. Zeke Emanuel pressed for more specificity on the steps where this pathway could be made more transparent. This is an action item for the industry to be further defined with more dialogue. One concrete example of how better understanding of a path to approval would affected a company’s effectiveness in producing countermeasures was given by Novartis regarding use of an adjuvant to increase immunogenicity of a vaccine. Adjuvants stimulate an immune response at a lower antigen concentration, and potentially produce a broadened response profile to similar antigens, thus increasing the manufacturing yield per unit of production. “In general, you can have more product produced if the material is more potent” was the phrase used to define this issue. In Europe, this pathway to use of adjuvant through their regulatory agency permitted the use of adjuvants in influenza vaccine, so what is the reason that the U.S. cannot seem to provide a reasonable pathway to accomplish a similar allowance ? There is a need for harmonization of the regulatory pathway with the EMEA (the European Medicines Agency) on issues such as this. It would also permit global companies more opportunity for accessing larger markets. Zeke Emanuel pointed out that the issue of adjuvants had to also account for the perceptions of safety by the U.S. population and must be factored into the market issues concerning this approach. Merck added an example regarding lack of a clear understanding of the regulatory path to have an anthrax lethal factor inhibitor approved. • Action item: identify what steps or processes are needed for international harmonization in regulatory pathways, with adjuvants as an exemplar • Action item: industry needs to be more specific in what steps should be taken to improve the FDA’s study review process (prospective vs. retrospective feedback). Liability It was noted by Merck that adequate liability is afforded to the industry on childhood vaccines (National Childhood Vaccine Injury Act), but that similar liability protections are not provided for adult vaccines. Dr. George Korch asked for clarification regarding whether protections under the PREP Act were not sufficient for the industry concerns regarding liability of products for biodefense and pandemic disease threats. There was no further discussion of liability issues at this time, and a due out to industry would be more definition of the nature of liability concerns that remain. (Note regarding the Prep Act: “Passed primarily to address the pandemic influenza threat, the PREP Act provides liability protections after a Secretarial declaration of covered countermeasures for any disease or health condition that the Secretary views as constituting a public health emergency, either presently or in the future. Liability protections cover the manufacture, testing, development, distribution, or use of the designated covered countermeasure absent willful misconduct”, source: http://www.hrsa.gov/countermeasurescomp/prep_act.htm as accessed on 30 January 2010) • An action item would be to have industry better define the nature of liability concerns that remain Partnering GSK commented on an issue regarding partnership models, and cited their ability to partner with the Defense Threat Reduction Agency as an example of how they are able to further progress on anti-infectives that may have dual utility for biodefense and for overall infectious disease markets. Another partnership example was the Wellcome Trust as a good example of effective partnership abilities. In this example, the company is covering costs of production of a malaria product, with an allowance for a small profit that is being turned back into research for additional malaria products. On a negative partnership experience, NKT pharmaceuticals described two examples of an inability to have easy access to National Institute of Health experts on an influenza antibody product and on an assay development (replacement of RBCs needed in hemagglutination assay) that took a great deal of time and paperwork to process and ultimately was resulted in no access. Someone pointed out one possible attributable factor is the stringent requirements by the NIH to avoid conflict of interest by employees. Novartis provided a suggestion on an tax credit incentive that would be viewed as favorable by big pharma and would stimulate partnerships with biotechnology companies. If the USG had a program where $ 40 M were available as tax credit to the company for partnering with biotechnology organizations to advance a promising technology or product within the biotech’s inventory, then it would serve in a similar way to a grant, but would have other advantages. For the USG, it would be a cost neutral opportunity to stimulate added partnerships, with potential spin off in licensing and access to technology. Manufacturing Capacity Big pharma did not express a concern about a lack of manufacturing capacity per se, but did indicate that rapid turn-around of production to a new product was difficult due to the regulatory approval of products that are site / locality specific. Merck said that it actually has excess capacity in some localities. The biotechnology sector said that they would love to have a manufacturing capacity issue. Merck indicated that overall, it would be happy to provide advice to the USG regarding manufacturing facility designs, etc. It was also understood that new facilities would have greater value if they were on U.S. soil. Small biotechnology Issues The disadvantage of the biodefense or public health emergency countermeasure market is that investors have no ability now to predict cost, return on investment, or timeline to return. Thus the biotechnology firms are looking for multiple ways to reduce the hurdles, with some examples pertaining to access to government and academia partners mentioned above. The SBIR program that would provide funding for small companies requires that the company not be more than 50% investor owned. It was suggested that this is set to change in legislation, but that the legislation is being held up waiting for health care legislation to proceed. At a programming level, lots of money was spent early on for very mature products to achieve approval, but there is less of an investment in early stage platform technologies to move them into position for scale-up and maturation. Many of the disruptive technologies come from the more risk-accepting smaller biotechnology companies, and there is not enough investment in the funds to realize gains faster. There needs to be more transparency on which scientists or investigators within the DoD and NIH programs are working on specific intramural programs to create a chance for more partnering with industry. Platform Technologies Dr. Tony Fauci asked about whether big pharma anticipates, or is pursuing any role in advancing platform technologies which would be transformative in the ability to realize dual marketing potential for products related both to public health emergency needs and to more commercially viable products. It would be preferable to share risk with big pharmaceutical companies in developing these platforms. Dr. George Korch also asked about prospects for host-based therapeutic targets for infectious agents vs. strictly pathogen based targets. Merck acknowledged the interest in host-based technologies, but in general there was no vibrant discussion of the platform approaches being considered by the industry at this meeting. There was a quick question as to whether stimulus funding should be applied to these broad-based platform technologies • Action item would be to expand inquiry regarding this approach to other companies, or to hold more one-on-one conversations with individual companies if there was a reluctance to disclose possible technologies now being addressed by these companies. • Another action item would be to determine what specific platform technologies would be estimated by industry as offering best return on investment. Other areas Regarding clinical studies, a suggestion was made that FDA should be allowed to explore less parametric and more Bayesian approaches to analysis of clinical trials data with a hope that it would allow for faster approval of products. The approaches for using the Animal Efficacy Rule were quickly discussed as needing much greater clarity from the FDA on how to accomplish approval under the rules. It was felt that there was a great deal of expertise in the DoD and NIH that would also contribute to industry’s needs. Regarding approval of medical products in general for public health emergency applications, one must account for the risk/benefit ratio of these products, relative to everyday products used for standard medical conditions and ask whether there needs to be some other lower threshold for approval of products that would be used under these higher risk scenarios. From: Korch, George (OS) Sent: Saturday, January 30, 2010 1:58 PM To: @who.eop.gov; @who.eop.gov; Emanuel, Ezekiel (NIH/CC/BEP) [E]; Ezekiel Emanuel; Lurie, Nicole (OS); Fauci, Anthony (NIH/NIAID) [E]; Robinson, Robin (OS); Merchant, Raina (HHS/ASPR); Borio, Luciana L (FDA) Cc: Korch, George (OS) Subject: Synopsis of Conversation with Pharma/Bio Reps 29 Jan 2010 Heidi, et al.: I have summarized the conversation with the VP's and representatives from the pharmaceutical / biotechnology industries regarding incentives promoting greater participation by industry in our public health emergency medical countermeasure enterprise. Where possible, I identify follow-on actions that derive directly from the conversation. There are still important conversations to continue with our commercial partners. Please feel free to modify or add information or perspectives that I did not adequately capture. Also, I did not quote by name the discussions offered by our industrial partners. Best regards George George W. Korch Jr. Senior Science Advisor Assistant Secretary for Preparedness and Response Department of Health & Human Services -----Original Message----- From: Korch, George (HHS/ASPR/IO) [mailto @hhs.gov] Sent: Saturday, January 30, 2010 1:58 PM To: @who.eop.gov; @who.eop.gov; Emanuel, Ezekiel J (NIH); Ezekiel Emanuel; Lurie, Nicole (OS); Fauci, Anthony S (NIH); Robinson, Robin (OS); Merchant, Raina (HHS/ASPR); Borio, Luciana Cc: Korch, George (OS) Subject: Synopsis of Conversation with Pharma/Bio Reps 29 Jan 2010 Heidi, et al.: I have summarized the conversation with the VP's and representatives from the pharmaceutical / biotechnology industries regarding incentives promoting greater participation by industry in our public health emergency medical countermeasure enterprise. Where possible, I identify follow-on actions that derive directly from the conversation. There are still important conversations to continue with our commercial partners. Please feel free to modify or add information or perspectives that I did not adequately capture. Also, I did not quote by name the discussions offered by our industrial partners. Best regards George George W. Korch Jr. Senior Science Advisor Assistant Secretary for Preparedness and Response Department of Health & Human Services