FDA, Clinical Trial Updates: Pro-Pharma Looks Promising

Includes: INVA, JNJ, MEDX, SGP
by: Mike Havrilla

Below is a summary of updates to the BioMedReports.com database of over 200 entries included in the FDA and Clinical Trial Calendars.

The FDA Calendar includes companies with pending new drug, biological agent, or medical device new product decisions at the FDA sorted by their PDUFA decision deadline dates while the Clinical Trial Calendar encompasses pending clinical trial results (with a focus on late-stage, Phase 3 trials), pending new submissions to the FDA (e.g. NDA, BLA, 510k, PMA, sNDA, sBLA filings), and pending re-submissions to the FDA for complete response rulings by the agency which require more information before an approval can be granted.
Theravance (THRX): On 4/24/09, the FDA accepted as complete for review Theravance's response to the February 2009 Complete Response Letter (CRL), which outlined requirements for approval of telavancin for the treatment of complicated skin and skin structure infections (cSSSI). Telavancin is a novel, bactericidal, once-daily injectable investigational antibiotic studied in the treatment of cSSSI and hospital-acquired pneumonia (HAP) caused by Gram-positive bacteria, including resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA). The PDUFA decision date for the cSSSI indication for telavancin is 9/16/09 while the decision date for the HAP indication occurs later in the year on 11/26/09.
Johnson & Johnson (NYSE:JNJ): On 4/24/09, SIMPONI (golimumab) recieved FDA approval as the first once-monthly anti-TNF treatment for three types of auto-immune arthritis conditions, including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Medarex (MEDX) is set to receive royalties on the drug as part of the UltiMAb (a technology platform for the development of human monoclonal antibody treatments) licensing agreement with JNJ while Schering-Plough (SGP) holds the exclusive marketing rights to Simponi outside of the U.S. (ex-Japan, Taiwan, and Indonesia).
In mid-April, Pro Pharma (OTC:PRWP) announced that a review of Phase 1 and 2 clinical trial data revealed that about 100 patients treated with the Company's lead compound in development called DAVANAT in combination with chemotherapy (including 5-FU regimens) experienced no incidence of mucositis serious adverse events (SAEs). Mucositis is a common side effect of many cancer treatments which can interfere with treatment and the ability to eat or drink normally. The condition causes painful inflammation, ulceration, and sores of the mucous membranes within the gastrointestinal (GI) tract.
The data also revealed that patients who received more than 100 cycles of cancer treatments with DAVANAT + 5-FU experienced no GI SAEs. 5-FU is a widely used type of chemotherapy drug that typically results in a 40% incidence of mucositis, including SAEs of grade 3-5, which can be life threatening and require hospitalization. There is an unmet medical need for an effective treatment for mucositis since cancer patients with severe cases may require treatment with narcotic pain drugs and intravenous (IV) feeding/hydration.
While mouth sores are typically nothing more than inconvenience for most people, mucositis is much more severe and affects the entire GI tract beyond just the mouth – resulting in poor absorption of fluids, nutrients, vitamins, etc. that can be debilitating and in some cases even life threatening. Having seen first-hand severe cases of mucositis in cancer patients while on rotation in pharmacy school six years ago; I know there is a major unmet medical need for a drug such as DAVANAT.
Once the drug is approved, doctors will be compelled to use it in combination with chemotherapy regimens such as 5-FU and irinotecan as the new standard of care since it eliminates the incidence of serious cases of mucositis while improving the anti-cancer effect of chemo drugs. PRWP is pursuing a dual strategy to obtain FDA approval as quickly as possible for DAVANAT by first conducting a pharmacokinetic (PK) study in 80 patients to get the drug approved as a functional excipient since the FDA has stated that no additional clinical trials or toxicity studies will be required as part of the 505(b)(2) pathway for modified formulation of drugs that are already approved.
The first stage for the planned DAVANAT label includes a 505(b)(2) NDA pathway by demonstrating increased bioavailability of chemotherapy drugs within the tumor and a reduction in serious side effects such as grade 3-5 mucositis. The second stage involves an amended NDA to demonstrate increased survival and reduced side effects based on results of the pending Phase 3 clinical trial in order to expand market share for the drug.
A Phase 1 clinical trial in 40 patients with solid tumors demonstrated that DAVANAT increased the half-life of 5-FU from 6-22 minutes when used alone to 28-137 minutes when used in combination, leading to an enhanced anti-cancer effect as the chemo drug persisted for a longer time period and decreased side effects when 5-FU was combined with DAVANAT.
DAVANAT is a carbohydrate-based polymer that interacts with specific receptors (galectins) on the cell surface which are over-expressed on cancer cells. Research also suggests that galectins impact the survival and spread of cancer cells. Results from a Phase 2 trial in late-stage colorectal cancer (CRC) patients revealed that administering DAVANAT along with 5-FU extended the median survival of patients to 6.7 months versus 4.6 months (a 46% increase in survival) while reducing the incidence of serious side effects by 41% (from 59% to 35%) as compared to the current standard of care treatments.
PRWP has filed a Drug Master File with the FDA for DAVANAT and the Company has a current Good Manufacturing Process (GMP) manufacturing facility with the capacity produce 1 million dosages of the drug per batch. DAVANAT is a new chemical entity which is a carbohydrate-based drug that is produced as an IV solution in 10mL vials as a clear, room temperature stable solution that can be combined with any type of chemotherapy drug or biological agent.
DAVANAT functions as a targeted therapy since galectins are over-expressed on cancer cells and the drug also increases the duration of activity of chemotherapy drugs. PRWP plans to initiate a Phase 3 clinical trial during 2Q09 and a bioavailability study later in the year during 3-4Q09. During 2H10, PRWP plans to file a NDA amendment based on survival data to increase market share.
At the end of March, PRWP reported its full-year operating results for 2008, which included an operating loss of $5.3M (down from $6.5M in the prior year) a net loss of $3.4M or ($0.07) per fully dilute shares (versus a net loss of $9.4M for 2007). R&D expenses for 2008 were $1.8M (versus $2.1M in the prior year) as the Company put two clinical trials on hold to conserve resources while focusing on the development of DAVANAT through the filing of the DMF (to support the Company's planned NDA filing with information about facilities, processes or articles used in the chemistry, manufacturing, controls, processing, packaging, and storing or stability of drugs).
PRWP ended the year with unrestricted cash of $318,000 and raised net proceeds of about $1.5M in a private placement transaction in mid-February. This transaction provides for up to $6M in financing through 10X Fund, L.P., through the purchase of convertible preferred stock and warrants. The initial closing involves the issuance and sale of 900,000 shares of preferred stock, which is convertible into 3.6M shares of common stock, class A-1 and A-2 warrants exercisable to purchase 3.6M shares of common stock, and class B warrants exercisable for the purchase of up to 7.2M shares of common stock.
The Company expects to complete one or more subsequent closings at some time before 8/11/09 for an additional 2.1M shares of preferred stock which is convertible into 8.4M shares of common stock, class A-1 and A-2 warrants for the purchase of up to 8.4M shares of common stock, and class B warrants exercisable for the purchase of up to 16.8M shares of common stock for aggregate, gross proceeds of $4.2M. PRWP expects to use the proceeds from this financing transaction to complete the submission of a NDA for DAVANAT, in addition to normal operating expenses.
PRWP also has a promising compound (PRO-GR 300) in preclinical development which has demonstrated the ability to reverse liver fibrosis (induced by the injection of a chemical toxin for eight weeks) in a rat model after just four weeks of treatment. These early stage results were enough to attract the attention of Dr. Scott Friedman, who is a member of the Company's Scientific Advisory Board and leads the liver disease division at Mount Sinai School of Medicine.
The U.S. market opportunity alone is significant for PRWP and DAVANAT, considering there are 150,000 new cases of CRC each year and 300,000 patients treated annually for the condition. An average of 50 doses of 5-FU are administered to each patient annually for CRC for a total of 15 million 5-FU doses per year. The estimated U.S. market for DAVANAT is $3 billion while the initial market opportunity includes 50,000 end-stage CRC patients, which equates to 2.5 million doses or a $500 million commercial opportunity for a stock that currently has a market cap of about $21M.
Disclosure: No positions.