Rxi Pharmaceuticals Corp (NASDAQ: RXII)
Rxi Pharmaceuticals last week on March 23, 2015 presented at the 73rd Annual Academy of Dermatology in which the company reported positive progress on clinical trial updates for its dermatology programs. The clinical trial with RXI-109-1301 phase 2a enrolled patients to be tested for hypertrophic scars on the abdomen only. In addition the company initiated a second Phase 2a hypertrophic scar study RXI-109-1402 that enrolled patients with scars in various locations on the body. Finally the company updated the Keloid trial RXI-109-1401 in which patients have their keloid removed in surgery and then receive an injection with RXI-109 to determine the recurrence effect of the keloid.
With respect to RXI-109-1301– hypertrophic scar study — the company reported already that initiating treatment with RXI-109 2-weeks post scar revision surgery displayed greater results than when initiating RXI-109 at the time of surgery. A blinded panel concluded that RXI-109 showed a greater effect over placebo at both the 1-month and 3-month intervals when RXI-109 was given to patients 2-weeks post surgery as opposed to immediately at surgery. With these finding the company then initiated RXI-109-1402 mentioned above in which the company will have to adjust dosing levels and provide more doses over the course of the scar proliferation phase — phase where scar continues to grow one year out. Study RXI-109-1301 patients are completely enrolled and further data will be evaluated at month 9. Study RXI-109-1402 is more than 50% complete on enrollment but patients continue to enter the study.
In respect to the keloid study RXI-109-1401 the company reported that the panel identified a greater recurrence of the keloid with the placebo treatment. This means that RXI-109 was doing a better job keeping keloids low on CTGF compared to placebo. The panel which was compromised of practicing dermatologists, plastic surgeons, and actual investigators in the study unanimously recommended that Rxi initiate a new trial with higher dosing and more doses over the course of the proliferation phase so that it can tackle the aggressive growth of keloids. This is good news because if the panel had concluded that placebo was performing better than RXI-109 then the panel wouldn’t have recommended for the company to continue with another keloid trial.
Rxi had a busy week because it had also announced that it had made a licensing deal with a privately held pharmaceutical company known as MirImmune LLC. The Company, MirImmune, will be developing cell-based cancer immunotherapy treatments using Rxi’s proprietary sd-rxRNA technology platform — self delivering siRNA molecules– using checkpoint inhibitors. Under the terms of the deal MirImmune will be responsible for all clinical costs relating to the development, manufacturing, regulatory and commercialization efforts of these cancer therapies. Rxi on the other hand will be receiving an annual licensing fee, clinical milestone payments, sublicensing income, and single digit royalties. If the trials produce positive results Rxi then has the option to buy a double-digit equity stake in MirImmune.
Merck & Co., Inc. (NYSE: MRK)
On March 24, 2015 Merck announced that it had obtained positive results in its phase 3 clinical trial program in patients with melanoma. The trial was stopped early because the results far exceeded those of the current standard of care therapy data. Melanoma is a type of skin cancer where the skin becomes damaged by DNA rearrangement. It is the most deadliest form of skin cancer and there are more than 120,000 people in the U.S. that were diagnosed with Melanoma in 2014. If the cancer is caught early then it can easily be treated but if it has spread to other parts of the body then it can be fatal.
The phase 3 trial known as KEYNOTE-006 recruited up to 834 patients who were split up into three different dosing groups in the study. The drug used by Merck to treat these patients with Melanoma is known as KEYTRUDA — pembrolizumab. The patients recruited in the study were stage 3 or stage 4 in Melanoma — advanced stages of cancer — who only had received one prior standard of care therapy. KEYTRUDA is a monoclonal antibody that is responsible for blocking PD-1 — programmed cell death receptor 1 — and its ligands PD-1/PD-2. The best current standard of care therapy for Melanoma at the moment comes from Bristol-Myers Squibb (BMY) which has developed a drug known as Yervoy — ipilimumab. Each one of the patients were classified into a certain dose group. Patients either took KEYTRUDA 10 mg/kg every 3-weeks, KEYTRUDA 10 mg/kg every 2-weeks, or 4 cycles of ipilimumab 3 mg/kg every 3-weeks.
The trial met the primary endpoints of two key objectives. The first primary endpoint tested progression-free survival and the other primary endpoint tested overall-survival. Merck met on both primary endpoints and in addition fared much better than the patients that took the placebo treatment ipilimumab. The full trial results though won’t be shown until some time in April where the company will present updated data at the 2015 American Association of Cancer Research Annual Meeting — AACR — which will take place in Philadelphia. In addition to positive clinical results in the phase 3 KEYNOTE-006 study the company reported that it would initiate a $10 billion dollar share repurchase program. Although the share repurchase program won’t take place all at once. Instead Merck will be buying its shares on the open market at various time intervals. Whether this will help the share price climb higher remains to be seen but the company is on the right track with its cancer drug which may prove to be successful in many other types of cancers as well.
Conatus Pharmaceuticals Inc (NASDAQ: CNAT)
Shares of Conatus Pharmaceuticals surged as high as 18% on March 26, 2015 after the company reported positive phase 2 results in its trial that treated patients with NASH which stands for non-alcoholic steatohepatitis. As the name suggests these patients have liver disease but not due too excessive use of alcohol. The phase 2 trial recruited just about 38 patients who either took 25 mg of emricasan or a placebo compound; both over a 28 day period. The primary endpoint of the trial was a measurement of NASH known as alanine amino transferase — ALT. These ALT are enzymes that are found on the cells of the liver and kidney. The company analyzed the results and determined that the p-value of p < .05 was statistically significant over placebo.
The liver needs ALT enzymes to survive but the problem is that NASH patients have too much of these enzymes which leads to a build up of fatty deposits in the liver. Looking more specifically into these results the ermicasan 25 mg group achieved an ALT enzyme reduction of 39% from baseline measurement while the placebo group only achieved a 14% ALT enzyme reduction. Even looking at the results in terms of percentages emricasan, Conatus’ drug, achieved more than double the reduction of ALT enzymes.
Why are these results exciting? Well for starters NASH drug development is a huge space because of the enormous market potential. Many analysts estimate that a NASH drug on the open market could possibly produce between $35 to $40 billion dollars by 2025. In addition the company has met with the FDA for early approval for emricasan based on a surrogate endpoint. A surrogate endpoint is a clinical efficacy measurement that the FDA establishes for a company to be able to file for early approval — Accelerated Approval.
Back in 2014 Intercept Pharmaceuticals (ICPT) reported that it stopped its phase 2 NASH trial early because the trial had met the primary endpoint in an interim analysis using its drug obeticholic acid — OCA. The Data safety monitoring committee has decided to stop the FLINT trial because of the positive data seen in the study. The patients saw a statistically significant improvement in histological data, obtaining a p-value of p < 0.0024 intent to treat, and in addition showed no worsening of fibrosis – scarring of the liver — as compared to placebo. Conatus may now be up to par with Intercept Pharmaceuticals but which one will win out in the end is up for grabs. Although considering the large market size for NASH we are pretty sure there will be plenty of room for both players in the space. In addition there are many other biotechnology companies who are working on NASH as well so we will just have to wait and see how the competition in this space persuades the market in the end.
Disclosure: Long Rxi Pharmaceuticals (RXII) , no position in other stocks mentioned