Greetings from a lovely day in Boston, where this year’s GTCBio Diabetes Summit has wrapped up, as we bring you our expanded highlights report from days #2 and #3. The last two days included a plethora of panel discussions that featured perspectives from everyone ranging from industry to academia to investors. We heard panelists from Novo Nordisk, Lilly, and Janssen comment on the potential for market differentiation in acquisition/licensing decisions, insights on the trend of tech companies entering diabetes, as well as specific thoughts on the field’s need for greater innovation. Please see below for top ten highlights and our reports from day #1 and day #2 if you haven’t yet.
1. In a panel discussion, Novo Nordisk’s Dr. Tomas Landh, Lilly’s Dr. Brian Bloomquist, and Janssen’s Dr. James Tobin noted that potential for market differentiation is a critical factor in the decision to license or acquire a particular product. The panel also discussed unmet needs within type 1 and type 2 diabetes, as well as the potential for combination therapies.
2. “Until we find the cure, he who owns behavior owns outcomes and the ability to extract value.” A panel on current trends and future predictions in diabetes focused on the entrance of technology companies into the diabetes arena and the growing interest in comprehensive disease management solutions.
3. An afternoon panel on “new approaches and emerging pipelines” was highlighted by strong enthusiasm for hepatic-specific insulin, while panelists shared low hopes for oral insulin.
4. Dr. Bruno Doiron (University of Texas, San Antonio, TX) forcefully argued that the bureaucratic and hierarchical nature of academia squelches true innovation by only supporting research that fits within established paradigms.
5. Dr. JoAnn Sperl-Hillen (HealthPartners Medical Group, Bloomington, MN) discussed the potential of electronic decision support tools to help primary care providers manage complex patients.
6. A panel discussion on partnerships discussed how fundamental differences in incentives between academia and industry can interfere with effective research collaborations.
7. NASH was labeled as an up-and-coming area in a panel discussion on investment trends in diabetes and obesity, as panelists pointed to its “overlapping of metabolic diseases” and high unmet need.
8. In the same investment trend panel, panelists pointed to the pitfalls of the obesity drug market and looked to bariatric surgery as an area inspiring new device development.
Top Ten Highlights
1. In a panel discussion, Novo Nordisk’s Dr. Tomas Landh, Lilly’s Dr. Brian Bloomquist, and Janssen’s Dr. James Tobin noted that potential for market differentiation is a critical factor in the decision to license or acquire a particular product. Dr. Bloomquist emphasized that, even for early-stage candidates, Lilly must believe that the eventual value proposition will be convincing to payers down the line. All three executives emphasized that the bar for reimbursement for diabetes drugs is rising considerably. Dr. Tobin pointed out that the branded drugs that have demonstrated a cardioprotective benefit (Lilly/BI’s Jardiance [empagliflozin] and Novo Nordisk’s Victoza [liraglutide]) will be generic by the time current early-stage pipeline candidates reach the market, meaning that potential new products will need to be able to demonstrate an even greater value proposition to justify a branded price. Dr. Landh shared that Novo Nordisk constantly receives pitches for different long-acting or rapid-acting insulin formulations and suggested that these products don’t offer enough differentiation. He suggested that new potential diabetes drugs in this environment must also offer cardiovascular or hepatic benefits. Dr. Bloomquist characterized this general approach to diabetes drug acquisition and development as “glucose-plus,” which he emphasized is absolutely critical to Lilly’s own approach as well. This discussion reinforced our sense that the bar for differentiation in type 2 diabetes is higher than ever before. While we recognize the increased pressures of the diabetes field, we hope these leading companies will continue to invest in new therapies given how many patients with diabetes are still unable to achieve their goals with existing options. As noted in another panel discussion, behavior management tools to help patients make better use of existing therapies also represent an area that is ripe for investment.
- The trio highlighted several unmet needs within both type 1 and type 2 diabetes. In type 1 diabetes, Dr. Bloomquist pressed for biomarkers that will enable researchers to better understand and predict the progression of the disease. He pointed to the many high-profile late-stage failures of type 1 diabetes therapies and suggested that there needs to be a better understanding of biomarkers to help industry mitigate the risk of investing in these therapies. The panel also expressed interest in glucose-responsive and tissue-selective insulins. That said, Dr. Landh emphasized that Novo Nordisk’s ultimate goal within type 1 diabetes is to develop a cure – hear hear! On the type 2 diabetes side, the panel agreed that insulin sensitizers would be very welcome. Dr. Tobin suggested that products that offer insulin sensitization indirectly through weight loss benefits, for example, would also be of interest. Diabetic nephropathy and NAFLD/NASH were both highlighted as areas of great unmet need that many pharmaceutical companies are interested in working in. Dr. Bloomquist quipped that “all of the players want to be in NASH,” though Dr. Tobin emphasized that candidates worthy of acquisition and substantial investment must be truly transformational and shouldn’t just be drugs originally developed for diabetes that failed their diabetes endpoints. That said, the lack of biomarkers and the rather long-term, intensive endpoints required for NAFLD/NASH and diabetic nephropathy studies were raised as barriers to entry by the panel. This echoes comments made at a similar panel at the recent Keystone Symposia meeting, though panelists at that meeting felt that diabetic nephropathy and NAFLD/NASH were among the diabetes complications that were more feasible to address (compared to, say, neuropathy). For an overview of industry investment in these areas, see our diabetic nephropathy and NAFLD/NASH competitive landscapes.
- As a whole, the panel agreed that combination therapies represent the future of diabetes therapy. Included in this category were fixed-dose and fixed-ratio combinations (such as Novo Nordisk’s GLP-1 agonist/basal insulin combination Xultophy [insulin degludec/liraglutide]), as well as polyagonists. Dr. Bloomquist shared that “everyone is working behind the scenes” on multiple-agonists for incretins, particularly GLP-1/glucagon dual agonists (for an overview of the companies who are publicly investing in this class, see our competitive landscape). Dr. Landh commented that it is “such a pleasure to have Dr. Richard DiMarchi at Novo Nordisk these days” – Dr. DiMarchi (Indiana University, Bloomington, IN) is at the forefront of novel polyagonist development and we’re particularly fascinated by his new “increlins” that offer triple-agonism at the GLP-1, GIP, and insulin receptors. That said, Dr. Bloomquist and Dr. Tobin noted that issues surrounding titration of the individual components of combinations remain a question.
2. “Until we find the cure, he who owns behavior owns outcomes and the ability to extract value.” A panel on current trends and future predictions in diabetes focused on the entrance of technology companies into the diabetes arena and the growing interest in comprehensive disease management solutions. Panelists Dr. John Brooks (Arete Worldwide, Medfield, MA), Dr. Mostafa Analoui (Livingston Securities, New York, NY), and Dr. Dave DeMarco (Ernst & Young, New York, NY) all highlighted the recent entry of “unusual players” like Google and IBM Watson into diabetes as a key trend in the field. They also emphasized that the healthcare field in general is moving away from selling specific compounds or services and focusing more on outcomes and behavior management. They acknowledged that the convergence of the healthcare and technology industries can lead to a culture clash, as tech companies are not used to the regulatory hurdles and slow pace of change in healthcare. However, they also agreed that both sides can learn from each other; as one example, Dr. Analoui noted that the quantitative data Fitbit collects for free from its consumers (e.g., what time people go to bed, how much sleep they get, how many steps they take per day) is the type of information that drug companies spend enormous amounts of money to gather. We feel that that greater collaboration between these sectors is absolutely a net positive trend; while it may be challenging for tech companies to adapt to the necessarily stricter regulatory environment of the healthcare industry, we believe they can contribute a great deal to making large-scale research more efficient and enabling more effective use of existing drugs and devices.
3. An afternoon panel on “new approaches and emerging pipelines” was highlighted by strong enthusiasm for hepatic-specific insulin, while panelists shared low hopes for oral insulin. Diasome Pharmaceuticals CEO Mr. Robert Geho opened the discussion, expressing a particular interest in insulin targeting the liver and pointed to relevant candidates in development at Lilly and Novo Nordisk. Other panelists Dr. Jerome Schentag (University of Buffalo, NY) and Ms. Lisa Jansa (International Diabetes Center, St. Louis Park, MN) chimed in with support, although Ms. Jansa discussed the reality that the established insulin market will make it challenging for the field to innovate beyond “the fringes.” We agree that hepatic-specific insulin is promising because it more closely mimics insulin’s physiological secretion; however, Lilly’s history of peglispro warrants caution around potential safety concerns. In addition, Ms. Jansa noted that there are many obstacles for oral insulin, as she pointed to bioavailabity and cost and compared oral insulin as similar to the disappointment of inhalable insulin. Dr. Schentag agreed that he doesn’t “see the current paradigm working for oral insulin” while Mr. Geho shared that it will be very important to distinguish between type 1 and type 2 diabetes with oral insulin. Indeed, we see oral insulin facing the challenge of ensuring that it doesn’t offer a “one size fits all” approach, as this could be very critical for any potential commercial success.
- Ms. Lisa Jansa (International Diabetes Center, St. Louis Park, MN) also called for greater innovation from regulatory officials to make way for new breakthrough therapies. She noted that many companies struggle to shift paradigms in their development of therapies due to the risks of breaking away from the “worn pathways” of familiar endpoints and regulatory responses. Thus, she highlighted that the FDA should move forward in accepting new endpoints and in identifying innovative biomarkers, as Dr. Schentag agreed that the FDA has only stuck to A1c as an endpoint, “oversimplifying the complex disease” of diabetes to glucose abnormality. We agree that regulatory agencies have a critical role in aligning the appropriate incentives and framework for therapy and device development and hope that greater conversation among industry, academia, and regulators can fuel this advancement.
4. Dr. Bruno Doiron (University of Texas, San Antonio, TX) forcefully argued that the bureaucratic and hierarchical nature of academia squelches true innovation by only supporting research that fits within established paradigms. He described the highest level of the scientific community as an “intellectual incest network” in which the same top labs, grant committee members, and pharmaceutical consultants engage in self-congratulation and recruit young scientists who will promote the same views. Dr. Doiron also offered a sharp critique of the current grant application and publication processes. On the grant side, he argued that researchers too often select projects based on the NIH’s interests rather than their own and that the lack of anonymity in the process leads to bias in favor of high-profile labs. He suggested that creating smaller grants that would be available to all researchers or even allocating grants randomly could help address this problem. On the publication side, Dr. Doiron argued (as several others have in recent years) that the enormous pressure to publish positive results in high-profile journals creates skewed incentives and leads to, among other problems, many published results that are not reproducible. He also asserted that “journalism for a lay audience with critical thinking is nonexistent in science” – while “nonexistent” might be an overstatement, we agree that the inaccessibility of science to the general population is a huge problem that likely contributes to the disconnect and even distrust many lay people feel toward the scientific and medical professions.
- A subsequent panel discussion on innovation covered similar themes, particularly the need for a greater diversity of perspectives in science. The panel, moderated by Dr. Dave DeMarco and featuring Dr. Christoph Pittius (AstraZeneca, Möndal, Sweden) and Dr. JoAnn Sperl-Hillen (HealthPartners Medical Group, Bloomington, MN) in addition to Dr. Doiron, agreed that including more viewpoints in the discussion can help spark more outside-the-box ideas. We particularly appreciated Dr. Sperl-Hillen’s comment that “the key to innovation is to listen to the audience you’re trying to innovate with.” In her case, gathering input from primary care providers and nurses was crucial for informing the design of a clinical decision support tool intended for the primary care community. Dr. Doiron also received some pushback from an attendee during the discussion over his blanket criticism of the scientific establishment and his portrayal of true innovation as coming from individuals rather than teams. We agree that certain elements of the current system, such as peer review of publications and grant proposals, are likely needed to ensure sufficient rigor, but Dr. Doiron’s point that academia needs to create more space for unconventional ideas is well taken. Greater funding for academic research and greater acceptance of publishing negative results are two solutions that we think could go a long way toward addressing these issues.
5. Dr. JoAnn Sperl-Hillen (HealthPartners Medical Group, Bloomington, MN) discussed the potential of electronic decision support tools to help primary care providers manage complex patients. She argued that even the most innovative drugs and devices for type 2 diabetes and obesity will have a limited impact unless they are incorporated into the primary care environment. She provided a brief overview of the CV Wizard tool developed by her group to help PCPs manage patients with multiple CV risk factors based on the latest evidence. The software, which is integrated into EHR systems, helps providers identify the highest-risk patients and prioritize treatment recommendations based on the likely benefit to a particular patient. It incorporates information about six CV risk factors – lipids, blood pressure, glucose, BMI, smoking, and aspirin/blood thinner use – and gives recommendations based on evidence from clinical trials and individual factors such as a patient’s current treatment and other comorbidities. It has been evaluated in several randomized controlled trials and demonstrated significant improvements in clinical outcomes. It has been implemented in several care systems in the Minnesota area, but Dr. Sperl-Hillen noted that the group hopes to license it to a partner with the resources to scale it up. We agree that such tools can be a very effective way to close the gap between the availability of innovative therapies and poor clinical outcomes in real-world practice. Our main questions relate to the user-friendliness of the software and providers’ willingness to accept it as a complement to their clinical judgment rather than a threat.
6. A panel discussion on partnerships discussed how fundamental differences in incentives between academia and industry can interfere with effective research collaborations. The panel included viewpoints from a variety of sectors, featuring former Joslin CEO Dr. John Brooks (Arete Worldwide, Medfield, MA), Vanderbilt’s Dr. Alan Cherrington, Pfizer’s Dr. Morris Birnbaum and Dr. Mary Julia Brosnan, Caladrius Biosciences’ Dr. Douglas Losordo, and the ADA’s Dr. Christopher Boynton. Key obstacles to collaboration cited on the academic side included an excessive focus on intellectual property protection and publication pressure that can interfere with reproducibility. On the industry side, panelists noted that companies often place too much emphasis on milestones and deliverables rather than letting the data shape future experiments. Several also noted that laws and perceptions surrounding conflicts of interest can make collaboration difficult. For example, there is stigma among some academics about working with industry, whereas the academics who have the closest relationships with companies (through consulting or serving on boards) are often precluded from conducting research with them. Despite these obstacles, the panelists all agreed that productive collaboration is possible when both parties are actively involved and share common interests. They also agreed that philanthropic organizations and venture capitalists can play an important role by funding innovative ideas that are too risky to attract interest from big pharma. Several panelists and attendees also highlighted the ability of organizations like the ADA and JDRF to help connect researchers with the communities they are working to help; Dr. Cherrington in particular spoke passionately about how volunteering for the ADA “brought a lot more meaning to what I was doing.” We especially appreciated the focus toward the end of the discussion on using patient-centric endpoints in studies and keeping patient communities informed about even very early-stage research.
7. NASH was labeled as an up-and-coming area in a panel discussion on investment trends in diabetes and obesity, as panelists pointed to its “overlapping of metabolic diseases” and high unmet need. Mr. Christopher Kiritsy (Arisaph Pharmaceuticals, Boston, MA) specifically suggested that the area is attractive due to its overlap with many different metabolic diseases as potential treatments’ inflammatory benefits can also blend in with fibrosis and steatosis. Similarly, he pointed to the more appealing regulatory pathway, which doesn’t require full outcomes trials and can have a faster route to approval due to the high unmet need of NASH, as companies can use this faster approval to then expand to broader indications such as diabetes or obesity. We have seen this strategy in action in some specialty obesity indications, such as Zafgen and Rhythm’s work in Prader-Willi syndrome and genetic obesity disorders. In addition, Mr. Richard Caroddo (Medpace, New York, NY) noted that there has recently been a “good amount of money thrown around” in NASH, as he highlighted the potential seen by payers: NASH treatment can help reduce costly conditions such as cirrhosis and expensive operations like kidney transplants. Indeed, as obesity rates rise, NASH prevalence is becoming an increasingly urgent public health concern, bringing along its high economic burden, as we have similarly sensed greater attention to the condition – see our coverage of a recent FDA AdComm meeting on Intercept Pharmaceutical’s obeticholic acid, which has generated significant interest due to its potential application in NASH.
8. In the same investment trend panel, panelists pointed to the pitfalls of the obesity drug market and looked to bariatric surgery as an area inspiring new device development. On obesity drugs, Mr. Kiritsy labeled the approved products as “incremental” improvements rather than “game changers” that struggled to build a market for themselves, with inadequate awareness prior to launch (although we feel that we see greater awareness building up now!). Mr. Mostafa Analoui (Livingston Securities, New York, NY) shared similar sentiments, stating that the products’ low to moderate weight loss are difficult to justify the costs and side effects. While these insights are valuable, they remind us of the expectations of the market and the public, which we believe sometimes disregard the powerful health benefits of 5%-10% weight loss (see our coverage of a Cell Metabolism paper on this). In addition, attendees and panelists commented that the obesity market is especially complex due to the success of therapies relying on lifestyle and behavioral change – a valid point highlighting the importance of patient education in this arena. Regarding bariatric surgery, the panel also pointed to this area as a promising one within obesity: Mr. Analoui highlighted the enthusiasm around devices that help make surgery “faster, safer, and reversible” while Dr. Peter Kolchinsky (RA Capital, Boston, MA) brought up devices “that give the benefits of bypass but feel more safe and less invasive” such as hydrogels and balloons. In our eyes, the device side of obesity has remained relatively quiet and slow; but we would agree that if bariatric surgery continues to gain attention and popularity, this market may accelerate more than we’ve seen, as the patient perspective gets louder with demand to fill the obesity treatment gap.
-- by Melissa An, Helen Gao, Emily Regier, and Kelly Close