Welcome to your weekly digest of approaching regulatory and clinical readouts. Top-line data from a phase III trial of Chiasma Pharma’s Mycapssa in acromegaly are expected in the third quarter. This is the group’s sole product, so a great deal is riding on the results.
The Optimal study is testing the capsule formulation of octreotide as a maintenance therapy in 56 acromegaly patients. Subjects will be randomly assigned to either placebo or Mycapssa, with the dose of the latter being titrated from 40mg to a maximum of 80mg per day. The highest dose regimen would consist of two capsules in the morning and two in the evening.
The inclusion of a placebo group was a hard-earned lesson for the company: an approval application for Mycapssa was rejected three years ago as it was based on a single-arm trial (Orphan miasma envelops Chiasma as FDA seeks new trial, April 19, 2016).
The enrolees in Optimal have confirmed active acromegaly based on elevated levels of IGF-1 – a byproduct of increased growth hormone – of at least 1.3 times the upper limit of normal. They must have taken injected somatostatin analogues such as Ipsen’s Somatuline for at least six months and responded, with IGF-1 levels dropping to less than 1.0 times the upper limit of normal.
Optimal’s primary endpoint is to maintain this biochemical response after eight months of Mycapssa therapy.
Chiasma is hoping that the data will allow it to position the drug as the first oral somatostatin analogue for the maintenance treatment of acromegaly, potentially replacing similarly-acting injected drugs as the pharmacological standard of care. If it achieves this Chiasma will see uplift in its shares, though the price is still unlikely to reach the highs of early 2016, before the FDA’s rejection.
It is not just Chiasma that will be hoping for a hit in the study. In addition to Chiasma’s transient permeability enhancer technology, the capsules are also formulated using Lonza’s liquid-filled hard capsule technology. Earlier this month the two groups extended the commercial supply agreement they first signed in 2012 and have anticipated the launch by investing heavily in manufacturing equipment; a trial failure would come as a hefty disappointment.
Assuming optimal Optimal data, a new NDA submission for Mycapssa is expected by the end of the year.
From cancer to MS
Arzerra never made it big in leukaemia, but Genmab and partner Novartis are hoping that the anti-CD20 antibody will enjoy a second lease of life in multiple sclerosis. In the second half of the year data from two phase III studies will help the groups decide whether a resurrection will be possible.
Novartis has put a subcutaneous formulation of the antibody, generically called ofatumumab, into two similar pivotal studies, called Asclepios I and II. According to clinicaltrials.gov the first trial is fully enrolled, with 929 relapsing MS patients, while the second is still recruiting, with a target of 900 relapsing subjects. Top-line data are expected in the coming months, and both use annualised relapse rate as the primary endpoint.
Both trials pit ofatumumab against Sanofi’s Aubagio, though Roche’s Ocrevus represents the real competition here. Ocrevus also hits CD20 and is already a blockbuster despite only launching in 2017, after the Asclepios trials got underway.
In terms of what is needed in the numbers to give ofatumumab a shot at a decent slice of the market, Ocrevus provides the gold standard. Roche’s antibody reduced annual relapses by around 80%, far surpassing the 55% reduction produced by Novartis’s Gilenya, which could soon lose patent protection. Aubagio managed 32%, so if ofatumumab fails to best the Sanofi drug, the project will be dead in the water.
Analysts at Bernstein have pointed out that in earlier studies ofatumumab generated very competitive responses on measures such as lesion reduction. An Ocrevus-like efficacy profile remains the bull case.
Safety will also be closely watched; should ofatumumab show any greater propensity to cause serious infections, malignancies or progressive multifocal leukoencephalopathy than other MS agents, it would have serious problems progressing.
Novartis has paid Glaxosmithkline, the original licensor of ofatumumab, $500m for rights in autoimmune conditions so far, and is on the hook for a further $534m, contingent on various milestones. Royalties of 12% also flow to Glaxo, and analysts at Bernstein reckon Genmab will be due a similar rate.
This could come to represent an important income stream for the small Danish drug developer, while Novartis will be hoping to find a new MS franchise growth driver. The sellside currently has sales of $871m pencilled in for subcutaneous ofatumumab in MS in 2024, according to EvaluatePharma consensus, but until the first pivotal data emerge, the real potential of ofatumumab’s new life is almost impossible to know.