Eating your way out of disease: An opinionated take on NEJM highlights for November 2018

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Peanut medicine that won’t cost peanuts

Allergy to peanuts is a major issue and though prevention is now possible in infants there is a huge population for whom actual survival is connected to vigilance in what they consume and availability of epi-pens. Desensitization to allergens is a well-established method to overcome an allergy, but it is typically done through injections, and it requires well calibrated micro-doses of the allergen.  Aimmune has been pursuing an oral approach with progressive dosing with peanut protein (AR101) and in a phase 3 trial, two thirds of the treated patients were able to tolerate a challenge with the equivalent of a few peanuts by the end of the study. This requires sustained daily ingestion of peanut protein though, and a major question that remains unanswered are the long-term health consequences of continued exposure to such an allergen – if one takes sprue for example – continued ingestion of gluten is often harmful.  Finally the major source of value for this product is its availability in precisely calibrated micro-doses which is important in the initial escalation process – but maintenance could likely easily achieved by eating a peanut every day.  AR101 Oral Immunotherapy for Peanut Allergy; Oral Desensitization to Peanuts (subscriber access)

 

A special kind of Omega-3

Even though the promise is there, almost all prospective randomized studies of nutritional interventions to decrease cardiovascular risk fail, including those involving omega-3 oil.  This is why the results of the ~5-year, 8000-patient randomized placebo controlled trial of icosapent ethyl – a highly purified and specific type of omega-3 now sold under the brand name Vascepa (Amarin) have attracted so much attention. In this high-risk patient population, on-going treatment reduced the risk of a significant CV event by about 25% relative to placebo, a number that is comparable or more to the benefit provided by PCSK9, and at about one third the cost (yearly treatment cost with Vascepa ~$4000). It’s a solidly executed study – except for one significant puzzle, the placebo group that received mineral oil had an increase in C reactive protein, a marker of inflammation that plays an important role in cardiovascular risk – did the observed effect of the trial have something to do with a negative impact of mineral oil on the placebo arm? Independently, cheap Omega-3 supplements are readily available in the health section of many stores – will the differentiated results drive actual prescribing and use of Vascepa? Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia; FISHing for the Miracle of Eicosapentaenoic Acid (subscriber access)

 

Leveraging innate immunity against cancer

Broadly speaking, the immune system is composed of two branches – acquired immunity for which the top representatives are T and B cells who can learn to recognize new pathogens, and innate immunity for which the top representatives are neutrophils and macrophages (Mφ) who are prewired to recognize certain classes of entities for attack and engulfment (phagocytosis).  Recent progress in immuno-oncology (I/O) has focused on the former (e.g. through PD-L1 inhibition), but now it appears that the latter could also be in play. Indeed many cancers express the “do not eat me” cell-surface receptor CD47 which inhibits phagocytosis. In a phase 1b study of 22 heavily pre-treated non-Hodgkins Lymphoma patients, blocking this receptor with the antibody Hu5F9-G4 (Forty Seven is the name of the company) while simultaneously giving rituximab resulted in half the patients having a response, and a third a complete response.   The mechanism of action appears to be that rituximab coats the cancer cells with antibody which are then eaten by Mφ because the cancer cells are no longer protected by a CD47 signal.  The potential for this technique to work with other cancers targeted with monoclonal antibodies is significant. CD47 Blockade by Hu5F9-G4 and Rituximab in Non-Hodgkin’s Lymphoma; Macrophage Checkpoint Blockade in Cancer — Back to the Future (subscriber access)

 

Fighting to last in multiple myeloma

These are nervous times for patients with multiple myeloma (MM) – MM is fatal, but a number of treatments stretch survival into the 4-5 years range (and sometime more). But now that potential CAR-T based cures are on the horizon, for many patients it’s no longer just about extending survival by months (or if lucky years), it is also about lasting till those new approaches make it to market. In that context, a study of elotuzumab (Empliciti, BMS-Abbvie) showing an extension of progression free survival by about 6 months in a patient population with multiple rounds of prior therapy is all the more meaningful. Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma (subscriber access)

 

The New England Journal of Medicine is a premier weekly medical journal covering many topics of interest to the health sector. In this monthly series we offer an opinionated perspective on selected highlights that might be of interest to our clients and others.