Out-the-box thinkers are just what the myelofibrosis treatment market needs

The pharmaceutical industry is an incredibly competitive space with new drug discoveries cropping up all the time, giving hope that we may soon find resolutions to the complicated medical challenges of today. 

The competitive nature of the space means that whoever is first to market has a clear advantage. Clinical stage pharmaceutical company Pharmaxis (ASX: PXS) is busy putting their lead asset PXS-5505 through its paces as an alternative monotherapy for the treatment of myelofibrosis, and other indications. 

But where does Pharmaxis stand in the greater clinical trial landscape of myelofibrosis treatment? What gives them an edge over competitors in the space?

First thing’s first- what actually is myelofibrosis? 

Myelofibrosis is a rare cancer of the bone marrow resulting in fibrosis, or scar tissue buildup, which in turn disrupts production of normal blood cells. This results in reduced immunity, bleeding issues and ultimately, poor patient outcomes. The disease portends a poor prognosis, with a life expectancy of merely 5 years after diagnosis.  Many patients go on to develop acute myeloid leukemia. 

Myelofibrosis is currently treated with a class of drugs called JAK inhibitors, namely Incyte’s Jakafi (ruxolitinib) and Impact Biomedicine’s Inrebic (fedratinib). Since launching in 2011, Jakafi has largely dominated the market, however there is significant unmet need in the myelofibrosis treatment market. 

JAK inhibitors are effective at reducing spleen size and improving disease-related symptoms; however, they are not suitable for every patient, nor do they meaningfully address the underlying cause of the disease.

Novel JAK inhibitors are emerging

In an effort to cash in on the $1 billion per annum market opportunity of myelofibrosis treatment, biotech companies worldwide are looking into new and improved JAK inhibitors and drugs with alternative mechanisms that could be used in combination  with JAK inhibitors. 

Sierra Oncology’s (NASDAQ: SRRA) momelotinib  and CTI BioPharma’s (NASDAQ: CTIC) pacritinib are both JAK inhibitors that also suppress additional biochemical pathways that contribute to myelofibrosis symptomatology, thereby reducing the disease burden. Both drugs have released data from phase 3 studies that show improvements in symptom control compared to existing standard of care including Jakafi but don’t show disease modifying effect that might significantly extend the lives on myelofibrosis patients.  Despite this analysts have forecast sales from momelotinib to exceed $350 million by the year 2027, flying past the $198 million that it cost to acquire the drug from pharmaceutical giant Gilead (NASDAQ: GILD) in 2018, whilst pacritinib sales are forecast to exceed $300 million.

Despite the mediocre outcomes of JAK inhibitors, companies and research groups are continually revisiting the process of JAK inhibition and co-activated pathways to see if there are ways to improve current treatments. 

Pharmaxis’ edge

Certain companies are looking beyond the JAK enzyme pathway for solutions. A compounding body of research has seen the scientific community build a robust knowledge of the biology behind myelofibrosis, which could turn treatment on its head. 

Giving patients an option after the failure of JAK inhibitor therapy is the new goal for several companies looking to target non-canonical molecular pathways. 

One of those pathways is the process of fibrosis. Lysyl oxidase (LOX) enzymes are increased in fibrosis and play an important role in fibrogenesis making them an obvious target for antifibrotic medications.

Pharmaxis’ designed PXS-5505 as an oral pan-LOX inhibitor, meaning it inhibits all lysyl oxidase enzymes. This mechanism of action has been demonstrated in preclinical studies to be disease modifying in patients with fibrosis, meaning that the drug could potentially be curative. 

The US FDA granted PXS-5505 both Investigational New Drug and Orphan Drug status, which aids in accelerating the approval process. 

PXS-5505 cleared Phase 1c safety trials with ease and is now undergoing Phase 2 trials in patients with myelofibrosis. Positive and promising results from Pharmaxis’ work has seen numerous renowned researchers and key opinion leaders seek out the Company for collaboration opportunities, one of which has led to the initiation of another Phase 2 trial. 

The significant unmet need for treatments that modify the course of myelofibrosis for patients already taking a JAK inhibitor or those who are JAK resistant is a massive commercial opportunity in the myelofibrosis treatment market and will continue to attract companies keen to cash in. The outside-the-box approach to the disease being taken by companies like Pharmaxis holds true promise as we pivot away from JAK inhibitors, towards treatments that target pathways that can treat both the symptoms and the underlying disease.

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Samantha Freidin

Samantha Freidin is a business journalist at Emerald Financial whilst also completing a Masters of Marketing and Digital Communications at Monash University.

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