Oral mucositis, or OM, is a very real problem for cancer patients, with essentially every head-and-neck cancer (HNC) patient receiving chemoradiation developing lesions in the mouth that can become so severe that the person can’t eat or drink and cancer therapy has to be suspended. Trying to be proactive, hospitals concoct their own “magic mouthwashes” to help alleviate the condition, but the proof is in the pudding that they just aren’t very effective.
That means hundreds of thousands of patients worldwide must deal with severe OM annually. With no FDA-approved drugs for the prevention of severe OM in HNC patients getting chemoradiation, it also means that there is a tremendous market opportunity available to help these people.
South Korea’s Enzychem Lifesciences estimates that a drug for chemo-radiotherapy induced OM would generate sales of $2.6 billion globally each year. Based on preliminary estimates of Innovation Pharmaceuticals (OTCQB: IPIX), the total OM market opportunity in HNC annually in the U.S. and Europe would be approximately $600 million to $1.2 billion.
If and when a drug is approved, a huge market is going to erupt. Private and government insurances can’t afford not to spearhead a movement to get an effective drug into patients considering each case of severe OM comes at an in-patient cost in the range of $18,000-$25,000. That goes without mentioning the better quality of life for patients.
A drug that is prophylactic would need to be given to all approximately 120,000 HNC patients in the U.S. and Europe at the outset of chemoradiation and continue throughout the treatment course. Now extrapolate that to the ~750,000 HNC patients worldwide. Further, factor in off-label use owing to the fact that up to 60% of patients receiving chemotherapy for their cancer, regardless of origin, develop OM.
Taking a look at the price of palifermin (trade name Kepivance) provides some guidance on potential pricing. Kepivance is the only drug available to treat OM, but it is exclusively indicated for hematopoietic stem cell transplantations, not solid tumors.
It is fair to estimate a new treatment could fetch between $5,000-$10,000 per course, lending credence to the estimates of both Enzychem Lifesciences and Innovation Pharma for a new blockbuster drug opportunity.
Despite the robust market potential, Wall Street doesn’t give a great deal of value to OM drugs in development, but that is something that could soon change.
Perhaps analyst’s bias is because no one has been successful yet at developing a drug. Maybe it is due to the fact that some “drugs” that made it to market weren’t actually drugs at all and ended up being commercial failures. For the most part, therapeutics that made it through the FDA’s 510(k) pathway – which qualifies them as a “medical device” and not a “drug” so they aren’t subject to the stringent qualifications to reach the market – are little more than magic mouthwashes. It makes sense that they don’t garner hospital adoption considering that they compete with the hospitals’ own magic mouthwash.
And, again, the fact is that they just don’t work very well as evidenced by statistics showing that some 60%-70% of HNC patients develop severe OM.
To that point, there is a huge difference between existing OM therapies and what companies like Innovation Pharmaceuticals (OTCQB: IPIX) and privately-held Galera Therapeutics are working on, respectively. These companies are each developing bona fide drugs to reduce the incidence, severity and duration of severe OM, but doing so with very different approaches.
Both companies are developing their experimental drugs under FDA “Fast Track” designations.
For its anti-OM strategy, Innovation Pharma is developing Brilacidin oral rinse, a “swish and spit” formulation of its potent and versatile lead drug candidate from a novel group of drugs called “defensin mimetics.” Innovation last year completed a Phase 2 trial of Brilacidin oral rinse that hit its primary endpoint in reducing the incidence of severe OM in HNC patients receiving chemoradiation, as well as other important readouts regarding shortening duration of severe OM and delaying the onset in cases where it did occur.
The data further showed that Brilacidin was particularly effective at reducing the onset of severe OM in patients receiving a more aggressive chemotherapy regimen (a higher concentration of cisplatin administered every three weeks). This is important to note because it is this regimen that is the standard of care today for cisplatin therapy.
In the per protocol population, the relative incidence of severe OM was reduced to just 14.3% compared to 72.7% in the placebo group.
Following an end-of-phase 2 meeting with the FDA, Innovation has the agency’s blessing to move forward with a pivotal phase 3 trial. This study will be of international scale, for which management is having a meeting this week with the European Medicines Agency (EMA) to ensure all protocols for the study are structured to meet European guidelines with the intent seek EMA drug approval in the future.
On Tuesday, Innovation said that it has made yield and purity enhancements in the manufacturing of Brilacidin for the bulk production of Phase 3 drug supply. While it might seem like a yawner to anyone but a scientist, the company is optimizing the chemical process as it looks up the road towards commercialization, should its trials be successful.
First up in those trials will be the phase 3 in OM, along with a new phase 2 trial to build upon a successfully completed study using Brilacidin for Inflammatory Bowel Disease.
For its part, Galera’s GC4419 is a first-in-class, small molecule enzyme mimetic that converts superoxide to hydrogen peroxide and molecular oxygen. GC4419 is administered through a 60-minute IV infusion.
After success in early and mid-stage trials, Galera in September began a phase 3 trial of GC4419 in patients with locally advanced, non-metastatic HNC receiving chemoradiotherapy. The trial’s primary outcome measure is cumulative incidence of severe OM.
Likely owing to the experience of Galera chief executive Dr. Mel Sorenson, the company has been extremely successful at raising capital to fund its research. Dr. Sorensen has raised over $300 million in multiple private financing rounds during his career and has led licensing deals for several preclinical and clinical-stage compounds, which has caught the eye of a bevy of investors. The company recently raised $150 million, broken down into a $70 million equity raise and an $80 million royalty financing payable from future sales.
Take note that investors are looking ahead to sales; those paying attention to the industry opportunity expect good things.
The completed Galera studies delivered compelling data about the efficacy of GC4419, including indicating that the drug decreases frequency of severe OM, delays the onset and shortens the duration when it occurs, much like that of IPIX.
In fact, Innovation Pharma has not been shy about putting data from each of their phase 2 trials side-by-side for comparison. This chart includes not only endpoint efficacy data for Brilacidin and GC4419, it also shows SGX942 (IV infusion) from Soligenix (NASDAQ: SNGX), Clonidine Lauriad (mucobuccal tablet) from Onxeo, now Monopar Therapeutics, and Kepivance (palifermin), marketed by Biovitrium.
While a smaller sample size, the data shows that Brilacidin was comparable across the study and outstripped the others in patients treated with high cisplatin regimens.
There is a feeling that something transformational is going to come to the OM space in the coming years, as Brilacidin, GC4419 and SGX942 move through their phase 3 studies. Anything can happen in the world of biotech, but it seems almost certain that one of these drugs will be the first ever approved by the FDA, quite possibly more than one. The intravenous drugs by Galera and Soligenix have a head start with regards to trials, but it is arguable that Innovation Pharma has the lead when it comes to ease of administration because patients prefer an oral therapy over IV and it can be administered in any setting, which keeps costs down and makes it appetizing to payers.