A recent New England Journal of Medicine had three articles and an editorial about hereditary angioedema previously called hereditary angioneurotic edema.   

By way of reminder, HAE causes recurrent episodes of swelling that can affect various parts of the body:  face, tongue, throat, abdomen, extremities.  It is caused by a gene mutation in SERPING 1 which controls the production of C1-inhibitor.  In type 1 HAE there is a deficiency of the inhibitor, in type 2 the inhibitor protein is present but non-functional.  Lack of C1-inhibitor leads to excess levels of bradykinin which causes the tissue swelling.   

Current treatment of HAE is two pronged:  prevention and rescue.   This strategy is very similar to the approach to chronic asthma; that is, using a daily controller medicine but also having a rescue inhaler.  There are several preventative therapies available.  There are two types (one IV and one injected sub-Q) of purified C-1 inhibitor.  There are drugs that inhibit the procession of brady kinin kallikrein.  (An injectable monoclonal antibody and also an oral kallikrein inhibitor).     There are injectable kallikrein inhibitors and injectable brady kinin receptor blockers.  These medications can be used for both prevention and for rescue from acute attacks.   

One of the new medicines discussed in the journal is donidalorsen (an antisense oligonucleotide) that inhibits the messenger RNA that would otherwise stimulate excess kallikrein production.  Donidalorsen is an injected medication but unlike other kallikrein drugs that require more frequent injection, it can be given every two months.   

The other new drug that was discussed in the journal is sebetralstat an oral kallikrein inhibitor designed to treat acute attacks.  Currently the only rescue medicines for acute attacks are all either IV or injected.  Being IV or injected leads to barriers to compliance:  effort needed to transport, store and prepare the medication and reluctance to self-injection or infusion.  Also, if the swelling involves the hands the patient is incapable of self-administration.  These issues are especially problematic in teenagers and have led to withholding of treatment and subsequent hospitalization or death.  This makes an oral rescue medication a welcome option.   

For the sake of completeness there is a third type of HAE with normal C-1 inhibitor but excess brady kinin that can occur due to other protein abnormalities.  This group is very rare.