Harnessing the collective wisdom of the world’s medical thought leaders.
Converting it into actionable insights for all stakeholders in disease management - Pharma, Payers, Clinicians, Regulators, Investors and most of all, Patients.
BOLT’s Though Leader Panels bring together the knowledge and expertise of the world’s best clinicians and researchers. Each Panelist is internationally recognized for their contributions to understanding and curing diseases.
There are a million consulting groups serving industry and the investment community. None are quite like us. We’ll give you unbiased thoughts and ideas from outside the echo chamber.
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Welcome to BOLT International
Latest News (November 2, 2015)
Ulcerative Colitis/Crohn’s TLP #20 2015-11 summarizes a series of thought leader interviews that were conducted in October 2015. For this panel, BOLT / MedPredict spoke with 6 internationally recognized experts in the treatment of inflammatory bowel disease. The purpose of this Panel was to identify the events that will reshape the IBD landscape in 2016/2017. Thought Leaders offered their perspectives on the significance of the approval of vedolizumab for Crohn’s and ulcerative colitis, TNF biosimilars, next-generation anti-integrins, JAK inhibitors, IL23 inhibitors, S1P agonists, SMAD7 inhibitors, IL-6 inhibitors and a variety of therapeutic approaches that are in earlier clinical / preclinical development.
The Panel offers insight in the following areas:
Anti-TNF positioning and sequencing in light of the vedolizumab approval.
IL-23 +/- IL-12: Stelara in treatment experienced Crohn’s. Role for IL-23 selective inhibitors.
JAK: Xeljanz infection risk in IBD.
The Panel specifically elaborates on the following Key Findings:
The IBD category will see two new approvals in 2016.
Ustekinumab will garner an approval in the US and EU for Crohn’s disease, with ulcerative colitis following about a year later. The drug will be available in both an infusion for induction and, if the physician and patient desire, an injection for maintenance.
Tofacitinib 10 mg b.i.d. will be approved on both sides of the pond for ulcerative colitis. It is probably a mistake to assume that the complete response letter to Pfizer regarding tofacitinib for psoriasis portends a negative judgment on the TOFA ulcerative colitis registration by either FDA or EMA.
About 25% of vedolizumab scrips are being written for anti-TNF naive patients. The response time is very long vs anti-TNF therapy, so the major drivers for choosing vedolizumab before anti-TNF are 1) patient’s disease burden – lower supports vedo use upfront), 2) patient’s infection risk, 3) patient’s aversion to biologics that increase infection risk and 4) cost (in Europe, vedolizumab is much less expensive than branded anti-TNF therapy)
Etrolizumab’s efficacy looks to be very similar to vedolizumab, in both ulcerative colitis, and the less well-studied Crohn’s population. The key product differentiation will be the dose form: vedolizumab is delivered as a 30 minute weight independent iv infusion. Etrolizumab is an injectable product. This Panel tends to see infusion as the better way to go, particularly in the Crohn’s population. However, vedo is a fixed dose, as opposed to e.g. infliximab which is weight based, and Panelists think the fixed dose limits their optimizing of a vedolizumab-based strategy.
Biosimilar anti-TNF is non-inferior to the parent brand when used in anti-TNF naive patients, but is inferior when switching due to antibody cross reactivity. Strategies to price the biosimilars at 20% below brand are being met by price matching by the innovator.
S1P agonists are more likely to have a long term therapeutic benefit than is mongersen.
NK cell inhibition is probably associated with better outcomes in IBD than is NK cell sparing.
Specialty/Location:Gastroenterology / N. America, Europe
Publication Date:November 2015
Principal Authors:Tricia L. Hanlon;Jeff Berk
If you are pharma, please contact Jeff Berk email@example.com for pricing for this report.
If you are a patient, please have your physician contact us for a free copy of this report. We do not distribute directly to patients.
(August 26 2014)
Reducing immunosuppression without allowing tumor regrowth, i.e. trying to prevent GVHD without abrogating the graft vs leukemia effect, is the Holy Grail of transplant biology. Like the Grail, really effective ways of achieving this goal haven’t been demonstrated in completed randomized trials. But there are, finally, plausible hypotheses to explain the underlying pathophysiology of graft vs host disease, and there are therapeutic approaches in the clinic that may capitalize on this new understanding.
The three problems after transplant that patients with malignant disease face are that they may have GVHD, their cancer may relapse, and they may have a fatal infectious complication. On the one hand, patients with six log reduction of AML, CML, CLL or myeloma are exceedingly unlikely to relapse, and physicians can be more focused on immunosuppression to reduce GVHD. Aggressive preventive therapy is limited mainly by the risk of increased infection. On the other hand, if the patient is progressing with their cancer it is generally a losing proposition to immunosuppress them, and the treater finds his options to be extremely limited. Net, monitoring the disease while trying to focus on the immunity constitution and avoiding GVHD is analogous to balancing on a three legged stool. You can’t win transplant without doing all three of those things. Setting aside the technical complexity of the operation, the solid organ transplanter, who doesn’t have to consider cancer relapse, has a relatively easier long term task.
BOLT / MedPredict’s Hem/Onc Thought Leader Panel (TLP) #39 summarizes the perspectives of six renowned US and European Thought Leaders who specialize in the treatment of graft-vs-host disease. The Ad Board was run in August 2014. This report updates the findings of a similar Ad Board conducted in the Summer of 2013. For tracking purposes, TL comments from the current Ad Board are in BLUE font, while those from the 2013 Ad Board are in GREEN font.
This report is 193 pages in length. It is organized by indication (acute, chronic, prevention, treatment), and then the mechanisms of action and drugs are grouped by their intended point of impact on GvHD pathophysiology: inflammation, lymphocyte trafficking, T-cell dysregulation, and end organ repair.
The Panel discussed the following topics / drugs:
GVHD – The big picture
Market Size (US, Annual)
GVHD Risk Factors
Prevention of GVHD in Allogeneic Transplant Patients
Myeloablative vs Non-Myeloablative Transplants
Chronic GVHD Prevention Trials
Acute GVHD Prevention Trials
Acute GVHD Treatment
Treatment of Acute GVHD (Steroid Responsive)
Protocols for Steroid-Responsive or Steroid-Incomplete Responder GVHD
Treatment of Acute GVHD (Steroid Refractory)
Chronic GVHD Treatment
Treatment Flowchart cGvHD
Treatment of cGvHD according to organs involved
Chronic GVHD Treatment Trials
Actemra RoActemra tocilizumab Roche
Anti-adhesion molecules Integrins, 47
vedolizumab / natalizumab / MadCAM
maraviroc (Selzentry) Pfizer
Dysregulated Immunity / Delayed Generation of T-Regs
Low Dose IL2 (Dana Farber)
high dose cyclophosphamide
Epigenetics: Hypomethylating Agents / HDACs
Zolinza (vorinostat; Merck)
CliniMACS (CD34 selection; Miltenyi Biotec)
Velcade (bortezomib; Takeda)
JAK (could have been filed under Lymphocyte Trafficking)
Jakafi Jakavi ruxolitinib
Mixed Donor Chimerism (NOTE: ONLY USEFUL FOR NON-MALIG TRANSPLANTS!)
Campath alemtuzumab + TBI + temsirolimus
ATG-Fresenius S: Neovii Biotech Fresenius
Gene Modified Donor T-Cells
B-Cell CD20 CD19 BTK
Rituxan / MabThera; rituximab (Roche)
ibrutinib (Pharmacyclics / Janssen)
CD19 CARS (Chimeric Antigen Receptor)
IL17 / IL23 / TH1 / TH17
End Organ Repair
Mesenchymal Stem Cells
Prochymal; remestemcel-L (Osiris)
MultiStem (Athersys / Pfizer)
F652 Generon (Shanghai China)
TGF / PDGF
Latest News (May 7 2014)
Cancer Immunotherapy; Melanoma, Non-Small Cell Lung Cancer, Renal Cell Carcinoma is the 38th hematology/oncology Thought Leader Panel published by BOLT International. We conducted in-depth interviews with ten peer recognized experts in the treatment of these three diseases. We asked them to summarize the successes and challenges in establishing immunotherapy as a co-pillar of modern cancer treatment along with chemotherapy and targeted therapy. And while other solid tumors can already be added to the list, the thought leaders focused on these three as they evaluated checkpoint inhibitors (certainly too narrow of a description), tumor infiltrating lymphocytes, biological response modifiers, vaccines and chimeric antigen receptors. This report captures their collective wisdom.
As with all of our reports, we (reasonably) expect that Pharma foots the bill, but if you are a patient with one of these diseases, we will gladly share WITH YOUR PHYSICIAN (he must directly contact us and ask) relevant excerpts.
In BOLT / MedPredict’s Psoriasis Thought Leader Panel #25 2013-12, seven of our experts (6 derms, 1 rheum; 4 US, 4 EU) in the treatment of moderate/severe psoriasis and moderate/severe psoriatic arthritis share their year-end views on the strengths and weaknesses of key competitors in development for these indications.
Psoriasis often appears between the ages of 15 and 25, but can develop at any age. Psoriatic arthritis usually develops between the ages of 30 and 50. Coupling these age of onset statistics with the experience that patients cycle through antipsoriatic therapy on average each 18-24 months, one realizes that there will be room for many new competitors in this space.
However, most of our thought leaders say that they will try two therapies from a class before moving on to a new mechanism of action. This tempers the commercial opportunity for the 3rd, 4th and 5th competitor unless there is a significant benefit to the patient, physician or payer.
For the patient, there is a new paradigm: reaching PASI 100 is an attainable goal for more than 50% of patients with moderate / severe psoriasis (see IL17 inhibitors). For the physician, “methotrexate without monitoring” offers a safe, easy to manage therapy (apremilast) for more moderate cases. For payers, biosimilar versions of etanercept (in the EU) and adalimumab (worldwide) are imminent.
Against this backdrop our Panel talks about the most recent trial data for the following mechanisms of action and molecules:
JAK: tofacitinib, baricitinib, GSK2586184, INCB039110, ASP015k, PF-04965842, ABT494
Fumarate: XP-23829, LAS-41008
(September 22, 2013):
Non-Small Cell Lung Cancer
BOLT / MedPredict NSCLC Thought Leader Panel #36, published September 2013, shares key insights gleaned from our Panel of experts in non-small cell lung cancer during interviews we conducted since ASCO 2013. This report focuses on adenocarcinomas and squamous cell carcinomas of the lung. There is little discussion of other lung cancers with partial or IHC adenocarcinoma differentiation (e.g. large cell carcinomas, small cell carcinomas or large cell endocrine carcinomas, brief comments on adenosquamous carcinomas in the section on the SQUIRE trial with necitumumab). The report is generally organized by target mechanism.
More than a decade since EGFR was identified as a substantial driver for adenocarcinomas, and five years since the importance of ALK fusions was shown, the targets for treatment of this histology has matured. We share our Panel’s opinions on next generation EGFR and ALK inhibitors, and newer targets: ROS, RET, HER2 and others.
In contrast, squamous cell carcinomas of the lung lack an approved targeted therapy. While less mature, it looks like this will change shortly, as FGF1 inhibitors make their way through development.
The major story in the solid tumor world this year has been the explosive development in the area of checkpoint modulation. There is speculation that PD-1 and other checkpoint approaches will be most beneficial in the squamous NSCLCs. The Panel reviews the safety and efficacy data presented on the PD-1 and PD-L1 inhibitors.
Finally, the Panel sheds light on PI3K in brain metastases, CDK4/6, HSP90 and other topics that will impact the changing landscape of NSCLC in the next few years.
Since BOLT’s first day of business in 1996, and MedPredict’s in 2006 we have been reachable to help our clients. Last July 4th one of our clients tracked me down in Northern Idaho (yes, they have cell phone service. Sort of) for an emergency project. But this year, come the end of July, some of us are going to Sierra Prieta (google it) to dig latrines and not shower for a week. We have this expression in our office: “That’s a 1st World problem”. Even as we work to help patients receive and Pharma develop new therapies for hard to treat diseases, we are working on 1st World problems. But “I have to carry water two miles this morning”, well, that’s definitely a 3rd World problem. And we want to get out of the office, out of Snottsdale AZ, and live for a week like most people on Earth do. It’s one thing to talk about solving the world’s problems; and sending money is pretty much just talk. It’s another to go lay pipe. So we’re going to dig ditches and lay pipe. See you when we’re back and showered.
Looking to access BOLT’s Syndicated Thought Leader Panel reports? Over the past 15 years BOLT International has moderated over 4,000 Thought Leader interviews across a wide range of therapeutic categories. These are summarized and analyzed in BOLT’s Thought Leader Panels; many of which are available to the public. Contact me by email to discuss pricing (firstname.lastname@example.org). We have recently installed a “buy now” feature on this website. There you will see our most current releases, available for instant purchase by credit card. If you don’t see what you want, ask. A note to patients: we discount our pricing (sometimes down to $0) to bona fide patients on a case-by-case basis – especially if our information will help you and your physician improve your care. Seriously, we’ll need a note from your doctor!
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“I’ve engaged Jeff Berk and BOLT International on numerous projects, at four different companies, over almost 20 years. He has his finger on the pulse of the current developments in Pharma, Biotech and Healthcare. His vast network of Thought Leaders is the best I have found anywhere. The depth and breadth of his advice has been helpful in many strategic decisions. Whether I’m calling him for a large due diligence project, or a quick piece of advice, he always has something insightful to share and the data to back up his opinion.” - U.S.-based VP Business Development, Pharma.