Celladon Corporation (NASDAQ:CLDN)
On April 26, 2015 Shares of Celladon Corporation tumbled 80% in one day after the company reported that its phase 2 trial using Mydicar to treat heart failure patients failed to meet on both the primary endpoint and the secondary endpoint. The phase 2 trial was known as CUPID-2 and recruited up to 250 patients in total who had heart failure. The patients were split up into two different treatment groups. One group took Mydicar gene therapy replacement and the other group took a placebo compound.
Mydicar is a class of drugs known as gene therapies in which companies attempt to build a gene in order to change the outcome of the patient’s disease. More specifically Mydicar builds a gene that is able to produce proteins known as SERCA-2 which help the heart muscle to expand and pump blood through the body more efficiently. This is because heart failure patients have abnormal levels of the SERCA-2 protein which leads to an unstable heart leading to heart failure.
As discussed above there were two different dose groups that were being measured in the study. The primary endpoint looked for time to recurrent heart failure events. Some examples of these recurrent heart failure events are ambulatory treatment for worsening heart failure, and heart failure related to hospitalization. The primary endpoint of the study failed completely in all regards.
The secondary endpoint looked for time to first terminal event such as: All Cause death, placement of a circulatory support device, or heart transplant. Now the miss of the secondary endpoint was another huge blow for Celladon’s future but wait it gets worse. That is because Mydicar also failed to improve in all other exploratory areas such as: Quality of life, 6-minute walk test, and improvement in heart association classification.
There is no doubt that Mydicars’ future has been completely put off track. At the moment Celladon’s main pipeline consists of Mydicar targeting other heart related problems. What does this mean? Well the fact that Mydicar failed to produce substantial phase 2 results against heart failure doesn’t bode well for these other programs in the pipeline. The company must next analyze the rest of the data to see what went wrong but don’t hope for a huge positive surprise out of these failed results. The company does have some pre-clinical candidates using stem-cells and a small molecule but for those to get into the clinic it will take years and even then we don’t know how efficacious those drugs will be. For now investing in Celladon is a total dart-board situation and why I think you should avoid it at all costs.
Some spill over damage did occur the day Celladon tanked down by 80% though. What happened was that other gene therapy stocks such as Bluebird Bio (NASDAQ:BLUE), UniQure (NASDAQ:QURE), and Spark Therapeutics (NASDAQ:ONCE) all fell down considerably on Celladon’s trial failure. But should all those other gene therapy companies have fallen in share price because of the failure of one biotech company? I don’t believe they should have, because while those companies use gene therapy for treatments their technology is established in a different way. For instance just like the RNAi companies not all of them use the same form of delivery method to deliver siRNA molecules into cells.
Management really failed investors on this press release big time though. That is because they gave the bad news to investors on a Sunday instead of a normal trading market day. Many investors were blindsided and angry afterwards, rightly so. Celladon for now may be good for a trade but i wouldn’t hold long term in a company that doesn’t take care of its shareholders properly.
Can-Fite Biopharma (NASDAQ:CANF)
On April 27, 2015 Can-Fite Biopharma surged as high as 51% after the company reported positive phase 2/3 results in patients with moderate-severe psoriasis. The new data the company reported suggests that it may be possible for the company’s drug, known as CF-101, to become first line therapy treatment for these patients with moderate-severe psoriasis. The phase 2/3 trial enrolled approximately 326 patients around the globe at multiple centers.
The primary endpoint of the trial was to be analyzed by the 12-week time point but the trial lasted out all the way to 32 weeks. The primary endpoint looked for the ability for the CF-101 drug to be able to show an improvement in the Psoriasis Area Severity Index — PASI — 75 score. This score though was being compared to how well the CF101 treatment worked compared to the placebo compound. Back in March 30, 2015 the company announced that it had failed to meet the primary endpoint of the trial at the 12-week time point compared to placebo causing the share price to collapse.
Many investors were left distraught and upset, of course, as a failing phase 2 trial is never a good thing for an early stage biotech. Although back in April Can-Fite reported further analysis of these psoriasis patients from week 16 to week 32. This additional data suggested that 20% of patients that took CF101 were able to achieve a PASI score of 90, meaning that 20% of these patients cleared 90% of their psoriasis. Remember Psoriasis is a devastating disease of the skin that persists and the fact that a lot of these patients were able to clear up to 90% of their skin is very impressive. This means now that Can-Fite may have the ability to eventually file CF101 as the primary first-line treatment for psoriasis which is huge.
Why is this result substantial? Well the reason being that patients with psoriasis don’t currently have a first line therapy approved by the FDA. This gives Can-Fite the opportunity to be the first game in town and reap in the revenue train that will ensure thereafter. Although depending on what the FDA decides the company may have to run another large confirmatory phase 3 trial to progress further to eventually file the NDA. One thing is clear though and that is with these additional results released the company has a bright future ahead of itself.
On April 29, 2015 Amgen announced that the FDA panel had backed its T-VEC vaccine for use in patients with Melanoma. What does this mean? Well this means that a panel of experts have backed this vaccine in a 21-1 vote for the approval of T-VEC. The downside? Well this isn’t the final vote, because ultimately it will be the FDA who decides if T-VEC should be approved for these patients with Melanoma. Although we can pretty much guarantee that the vaccine should be approved by the FDA because while the FDA doesn’t have to back the panel of experts, they typically don’t go against their vote either. This is especially true considering the vote was 21-1 which by my standards is a huge landslide victory for T-VEC.
The T-VEC vaccine is a genetically modified version of the Herpes simplex virus. What does this mean? This means that the genetic code has been made closely similar to the Herpes Simplex Virus but not exactly like it. In addition Amgen modified the vaccine so that it only replicates in cancerous cells only. This means if T-VEC reaches healthy cells in the body the T-VEC molecules will not replicate in them, instead nothing will occur. It doesn’t stop there because T-VEC has an additional function that boosts the efficacy of the compound. T-VEC also uses a protein, known as GM-CSF, which has the main function of calling out to the patient’s immune cells to come and kill the tumor — kind of like a shouting call telling your immune system what and where it should attack.
FDA notes that came out a few days before the panel vote noted some caution from the FDA stating that T-VEC didn’t meet the secondary endpoint of the trial of Overall Survival. Although T-VEC did pass the primary endpoint achieving a 16% durable response rate compared to a placebo compound. One thing to note though is that the secondary endpoint of Overall Survival was only missed by a small margin, so it’s not like it completely missed. The efficacy and safety seem to be good for T-VEC but it is clear that it will have tough competition upon entering the market due to competitors. Such competitors are Merck (NYSE:MRK) and Bristol-Myers Squibb (NYSE:BMY) respectively.