Linzess Vs. Plecanatide
Jan. 19, 2017 5:40 PM ET
Synergy Pharmaceuticals (NASDAQ: SGYP) is currently waiting for an answer from the FDA on their prized drug, Plecanatide. Plecanatide treats both chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). The drug's main competitor is Linzess, which has been on the market since 2012, treats the same conditions and is marketed by both Ironwood Pharmaceuticals (NASDAQ: IRWD) and Allergan (NYSE: AGN) among others. As mentioned, the FDA has a goal date of January, 29th for the potential approval of Plecanatide for CIC, which is a much larger market than IBS-C.
Several articles have been released comparing certain endpoints from the various clinical trials conducted by these companies. Synergy seems to have a clear edge. Synergy is just as good, if not better, than Ironwood in terms of the CSBM responder endpoint. Synergy will also own the first drug approved for these conditions having to meet the FDA's more stringent regulations. The main differentiator for Synergy, and a major selling point, is the diarrhea rate. Plecanatide has shown less than 6% diarrhea for both indications, while Ironwood has shown 20% in IBS-C and 16% in CIC. There are a few other alarming points regarding Linzess that has not been talked about.
If you were to read the full prescribing information for Linzess you'll notice that 8% of Linzess patients discontinued prematurely due to adverse reactions, while Plecanatide showed 3.2%. Ironwood also mentions that 5% of patients discontinued due to diarrhea specifically compared to just 1.1% with Plecanatide, but here is the most alarming point. A large amount of Linzess patients, 27% to be exact, had their dose reduced or suspended due to adverse reactions (mainly diarrhea). What most people don't know is that treatment suspensions/interruptions were not allowed under any circumstances for Plecanatide studies. Treatment suspensions were allowed in the Linzess studies, which means a lot of the percentages above regarding Linzess probably would have been much higher if they were not allowed.
Another alarming issue that doesn't get attention is found within the review packet by the FDA for Linzess. Reading this you will find specific concerns the FDA had for the drug. The biggest issue is immunogenicity. There is currently a Phase IV trial being conducted by Forest Laboratories. The trial is testing the immunogenicity of Linzess for both CIC and IBS-C. This is a trial that was specifically requested by the FDA because of their concerns regarding the drug. Basically, there is a concern of "unwanted immunogenicity". Meaning, Linzess could have an immune response on patients that would significantly reduce the effectiveness of Linzess, and may even induce additional adverse effects. The trial is expected to be completed in March 2018 and is utilizing all Linzess doses (72, 145 and 290 mcg).
It should also be noted that Linzess ran clinical trials in Japan under their newest dose, 72 mcg. Some consider this lower dose, and additional trial, as a way to mitigate the threat of Plecanatide and lower the high diarrhea rates in Linzess. The trial was completed and results were issued in October 2015. Unfortunately, the diarrhea rates and even the primary endpoint in the trial have never been stated despite the "positive results". It is fair for one to assume that Linzess did not narrow the gap between overall efficacy compared to Plecanatide, along with the larger gap in diarrhea.
In conclusion, Plecanatide is a much better option for patients, should easily be approved and could potentially bring around $1 billion in peak sales. Buyout talk and commercialization talk would warrant a separate discussion, but it should be noted that Synergy owns 100% worldwide rights to Plecanatide, while Ironwood owns less than 50% for Linzess. Gary Jacob, CEO of Synergy, has noted numerous times that it is the company's main goal to retain those 100% rights, as it would bring maximum value to shareholders. Takeda would probably be the number one target for Synergy. Takeda recently mentioned in their latest corporate presentation that their focus is on Oncology, GI and CNS. They went further and identified "GI motility diseases" as an area of interest, which would mean chronic constipation and irritable bowel syndrome among others. Shire, Allergan, Pfizer, AstraZeneca could also be targets, along with companies that may want to start an all-new focus in GI. Plecanatide would be a great starter drug for a company like AbbVie or someone else who wanted to start a new focus in GI.
Jan. 19, 2017 5:40 PM ET
Synergy Pharmaceuticals (NASDAQ: SGYP) is currently waiting for an answer from the FDA on their prized drug, Plecanatide. Plecanatide treats both chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). The drug's main competitor is Linzess, which has been on the market since 2012, treats the same conditions and is marketed by both Ironwood Pharmaceuticals (NASDAQ: IRWD) and Allergan (NYSE: AGN) among others. As mentioned, the FDA has a goal date of January, 29th for the potential approval of Plecanatide for CIC, which is a much larger market than IBS-C.
Several articles have been released comparing certain endpoints from the various clinical trials conducted by these companies. Synergy seems to have a clear edge. Synergy is just as good, if not better, than Ironwood in terms of the CSBM responder endpoint. Synergy will also own the first drug approved for these conditions having to meet the FDA's more stringent regulations. The main differentiator for Synergy, and a major selling point, is the diarrhea rate. Plecanatide has shown less than 6% diarrhea for both indications, while Ironwood has shown 20% in IBS-C and 16% in CIC. There are a few other alarming points regarding Linzess that has not been talked about.
If you were to read the full prescribing information for Linzess you'll notice that 8% of Linzess patients discontinued prematurely due to adverse reactions, while Plecanatide showed 3.2%. Ironwood also mentions that 5% of patients discontinued due to diarrhea specifically compared to just 1.1% with Plecanatide, but here is the most alarming point. A large amount of Linzess patients, 27% to be exact, had their dose reduced or suspended due to adverse reactions (mainly diarrhea). What most people don't know is that treatment suspensions/interruptions were not allowed under any circumstances for Plecanatide studies. Treatment suspensions were allowed in the Linzess studies, which means a lot of the percentages above regarding Linzess probably would have been much higher if they were not allowed.
Another alarming issue that doesn't get attention is found within the review packet by the FDA for Linzess. Reading this you will find specific concerns the FDA had for the drug. The biggest issue is immunogenicity. There is currently a Phase IV trial being conducted by Forest Laboratories. The trial is testing the immunogenicity of Linzess for both CIC and IBS-C. This is a trial that was specifically requested by the FDA because of their concerns regarding the drug. Basically, there is a concern of "unwanted immunogenicity". Meaning, Linzess could have an immune response on patients that would significantly reduce the effectiveness of Linzess, and may even induce additional adverse effects. The trial is expected to be completed in March 2018 and is utilizing all Linzess doses (72, 145 and 290 mcg).
It should also be noted that Linzess ran clinical trials in Japan under their newest dose, 72 mcg. Some consider this lower dose, and additional trial, as a way to mitigate the threat of Plecanatide and lower the high diarrhea rates in Linzess. The trial was completed and results were issued in October 2015. Unfortunately, the diarrhea rates and even the primary endpoint in the trial have never been stated despite the "positive results". It is fair for one to assume that Linzess did not narrow the gap between overall efficacy compared to Plecanatide, along with the larger gap in diarrhea.
In conclusion, Plecanatide is a much better option for patients, should easily be approved and could potentially bring around $1 billion in peak sales. Buyout talk and commercialization talk would warrant a separate discussion, but it should be noted that Synergy owns 100% worldwide rights to Plecanatide, while Ironwood owns less than 50% for Linzess. Gary Jacob, CEO of Synergy, has noted numerous times that it is the company's main goal to retain those 100% rights, as it would bring maximum value to shareholders. Takeda would probably be the number one target for Synergy. Takeda recently mentioned in their latest corporate presentation that their focus is on Oncology, GI and CNS. They went further and identified "GI motility diseases" as an area of interest, which would mean chronic constipation and irritable bowel syndrome among others. Shire, Allergan, Pfizer, AstraZeneca could also be targets, along with companies that may want to start an all-new focus in GI. Plecanatide would be a great starter drug for a company like AbbVie or someone else who wanted to start a new focus in GI.