Here Are Two Phase II Trials To Watch: Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY) and argenx SE – American Depositary Shares (NASDAQ:ARGX)


This week we got word of two phase II trial initiations, both of which have the potential to serve up numerous catalysts for the companies sponsoring them. Here’s a look at both studies, the companies that are running them and the drugs involved.

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The two companies in focus are Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY) and argenx SE – American Depositary Shares (NASDAQ:ARGX).

So, let’s kick things off with Alnylam.

This company announced on Wednesday that it was initiating a phase II study of a drug called Cemdisiran (ALN-CC5). The trial is geared towards the treatment of patients with what’s called atypical hemolytic-uremic syndrome (aHUS). This is an extremely rare condition that can be both life-threatening and progressive in sufferers and, while the cause is a little bit opaque (in the sense that there are differing opinions on the root cause) the condition generally has a genetic component and this makes it difficult to treat.

It’s generally regarded as being caused by an uncontrolled activation of what’s called the complement system, which is the branch of the body’s immune system that destroys and removes foreign particles.

(As a quick note on the above two sentences – we know it’s rooted in activation of the complement system but we don’t know exactly what causes said activation).

Anyway, as mentioned, the drug is called Cemdisiran and it’s what’s called an investigational RNAi therapeutic, which targets the C5 component of the complement pathway. This C5 component is predominately expressed in liver cells and the idea is that through mediation of C5, the attenuation of the immune system can, in turn, be mediated.

That’s the theory, at least.

The trial in question is set up to validate this theory and it follows some early stage investigations that seem to have demonstrated that the drug can be safe in this patient population. It’s going to follow an adaptive study design with an initial cohort of 12 aHUS patients who are not currently treated with an anti-C5 monoclonal antibody. Each of the patients in the study will receive a 600 mg dose of the drug once every four weeks and, based in the adaptive design element of the study, each patient has the choice to increase or decrease dosing as the study matures and based on their personal interpretation of the effect that the drug is having on their condition and their health in general.

As far as study goals are concerned, the primary endpoint of the investigation ss normalization of platelet counts, with secondary endpoints including hematologic and thrombotic microangiopathy (TMA) response, improvement in renal function, safety and tolerability.

From a timeframe perspective, Alnylam expects to report initial clinical proof of concept data from this trial in late 2018.

Moving on, let’s look at Argenx.

This trial is set up to investigate a drug called ARGX-113 as a potential therapy for patients with a condition called pemphigus vulgaris. This one is far more common than the disease that Alnylam is going after but this far from reduces the unmet need (if anything, it expands it). Pemphigus vulgaris is an autoimmune disease characterized by blistering and sores (erosions) of the skin and mucous membranes. In patients with the condition, their immune system produces antibodies that attack certain proteins in the skin and mucus membranes. These antibodies cause the bonds between skin cells to break down, which results in the blisters and sores associated with the condition.

The current treatment landscape is pretty sparse, with high strength steroids essentially the only standard of care option in the space. The way ARGX-113 works is by blocking a process called antibody recycling, which is a key process in the production and replication of antibodies. By blocking antibody recycling, the theory is that the store of antibodies that attack the skin cells should deplete, and do so quickly, and this should essentially cure the disease.

The primary endpoints of this one are safety and tolerability (standard endpoints with this sort of investigation), and secondary endpoints include efficacy and an assessment of pharmacokinetics (PK) and pharmacodynamic (PD) markers.

The company hasn’t yet reported a specific target for topline but intends to present the trial design in more detail at a conference in November, at which point we should get the information we’re looking for.

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