ProLindac Produces 66% Disease Stabilization In Heavily-Pretreated Patients Within Phase II Study High Dose Groups

“… ACCESS PHARMACEUTICALS, INC. … , announced today positive safety and efficacy results from its Phase 2 monotherapy clinical study of ProLindac(TM) in late-stage, heavily pretreated ovarian cancer patients. In this monotherapy study 66% of patients who received the highest dose achieved clinically meaningful disease stabilization according to RECIST [Response Evaluation Criteria in Solid Tumors] criteria. No patient in any dose group exhibited any signs of acute neurotoxicity, which is a major adverse side-effect of the approved DACH platinum, Eloxatin, and ProLindac was well tolerated overall. The maximum tolerated dose of ProLindac was established as well as the recommended dose levels for future combination studies. …”

66% of evaluable heavily-pretreated patients in the high dose groups achieved disease stabilization. ProLindac was well tolerated overall.

DALLAS, March 5 /PRNewswire-FirstCall/ — ACCESS PHARMACEUTICALS, INC. (OTCBB: ACCP), announced today positive safety and efficacy results from its Phase 2 monotherapy clinical study of ProLindac(TM) in late-stage, heavily pretreated ovarian cancer patients. In this monotherapy study 66% of patients who received the highest dose achieved clinically meaningful disease stabilization according to RECIST [Response Evaluation Criteria in Solid Tumors] criteria. No patient in any dose group exhibited any signs of acute neurotoxicity, which is a major adverse side-effect of the approved DACH platinum, Eloxatin, and ProLindac was well tolerated overall. The maximum tolerated dose of ProLindac was established as well as the recommended dose levels for future combination studies.

‘We are very pleased with these results. ProLindac was well tolerated in an absolute sense and relative to commercially-available platinum therapies. We saw significant DACH platinum activity and efficacy in patients at the highest dose levels which is very encouraging given that this study involved monotherapy in a heavily pretreated patient population that typically only respond to an aggressive drug combination,’ commented Dr. David Nowotnik, Access’ Senior Vice President R&D. ‘The DACH platinum activity level seen benchmarked favorably with published studies of monotherapy oxaliplatin in similar but less heavily pre-treated patient populations. Having achieved the recommended dose for future combination studies, we look forward to moving ahead in the clinic ourselves and with our regional partners.’

This 26 patient Phase 2 study explored 3 different dose levels and 2 dosing regimens of ProLindac as a monotherapy treatment for advanced ovarian cancer, to provide data on the monotherapy anticancer activity and safety of ProLindac. Of patients eligible for evaluation according to standard RECIST criteria, clinically-meaningful disease stabilization was achieved in 42% of all patients, and 66% of all patients in the higher dose groups. Sustained and significant reductions in Ca-125, the established specific serum marker for ovarian cancer, were also observed in several patients.

‘We are delighted that the results from this study support our belief that ProLindac is an active platinum agent with a favorable side effect profile,’ stated Jeffrey B. Davis, Access’ President & CEO. ‘These data provide us with a strong incentive to continue the clinical development of ProLindac. As previously announced, we are currently planning a number of combination trials, looking at combining ProLindac with other cancer agents, such as taxol and gemcitabine, in multiple solid tumor indications including colorectal and ovarian.’

Access has previously announced that it has licensed ProLindac to Jiangsu Aosaikang Pharmaceutical Co., Ltd. (“ASK”) for the Greater China Region and to JCOM, Ltd for South Korea. Under these agreements both of these partners will be conducting Phase 2 combination studies with ProLindac in specific tumor types at their expense based on these results. Access is currently in discussion with potential partners for development and commercialization of ProLindac in additional territories.

About ProLindac(TM):

ProLindac is a novel DACH platinum prodrug which has been shown to be active in a wide variety of solid tumors in both preclinical models and in human trials. Access believes that ProLindac’s unique molecular design potentially could eliminate some of the toxic side effects seen in the currently marketed DACH platinum, Eloxatin, which has sales in excess of $2 billion.

About Access:

Access Pharmaceuticals, Inc. is an emerging biopharmaceutical company that develops and commercializes propriety products for the treatment and supportive care of cancer patients. Access’ products include ProLindac(TM), currently in Phase 2 clinical testing of patients with ovarian cancer, and MuGard(TM) for the management of patients with mucositis. The company also has other advanced drug delivery technologies including Cobalamin(TM)-mediated targeted delivery and oral drug delivery, its proprietary nanopolymer delivery technology based on the natural vitamin B12 uptake mechanism; Angiolix(R), a humanized monoclonal antibody which acts as an anti-angiogenesis factor and is targeted to breast cancer; Prodrax(R), a non-toxic prodrug which is activated in the hypoxic zones of solid tumors to kill cancer cells; Alchemix, a chemotherapeutic agent that combines multiple modes of action to overcome drug resistance. Access is also developing Phenylbutyrate (“PB”), an HDAC inhibitor and differentiating agent currently a Phase 2 clinical candidate. Access recently announced the acquisition of MacroChem Corporation. This acquisition provides Access with three additional late-stage product candidates. Pexiganan, a novel topical anti-infective for the treatment of diabetic foot infection, has already completed two Phase 3 trials. EcoNail is a topically applied econazole lacquer based on Access’ proprietary SEPA polymer technology, for the treatment of onychomycosis, a condition commonly known as nail fungus. Thiarabine is a new generation nucleoside analog which has demonstrated both pre-clinical and clinical activity in certain cancers. For additional information on Access Pharmaceuticals, please visit our website at www.accesspharma.com.

This press release contains certain statements that are forward-looking within the meaning of Section 27a of the Securities Act of 1933, as amended, and that involve risks and uncertainties. These statements include those relating to: clinical trial plans and timelines and clinical results for ProLindac and product candidates acquired in the MacroChem transaction, our ability to execute licensing agreements in the future, Access’ plans to continue and initiate clinical trials, the value of its products in the market, its ability to achieve clinical and commercial success and its ability to successfully develop marketed products. These statements are subject to numerous risks, including but not limited Access’ need to obtain additional financing in order to continue the clinical trial and operations and to the risks detailed in Access’ Annual Reports on Form 10-K and other reports filed by Access with the Securities and Exchange Commission.”

Quoted Source66% of evaluable heavily-pretreated patients in the high dose groups achieved disease stabilization. ProLindac was well tolerated, Press Release, lAccess Pharmaceuticals, Inc., March 5, 2009.

2 thoughts on “ProLindac Produces 66% Disease Stabilization In Heavily-Pretreated Patients Within Phase II Study High Dose Groups

  1. This is great–thanks so much. There are plenty of attractive Phase II results that don’t make it to “prime time,” randomized Phase III trials, but here’s hoping we have a winner on our hands.
    Disease stabilization is a “soft” endpoint to report. The Cadillac endpoint to report is really survival benefit, and that is usually what the FDA requires for approval, except in cases where there are no meaningful alternatives. Disease stabilization may be sufficient, depends on how ODAC is voting that week, and whether FDA listens to them (as sometimes it doesn’t–look at how Avastin got approved in breast cancer over the objections of ODAC).
    InteractMD.com

    Like

    • Michael,

      It is always great to receive your comments, especially given your “real world” oncology expertise. I agree with your comment in full. In fact, “stable disease” and “partial response” measures are subject to interpretation (and potential bias or error) under the RECIST criteria. Anyone who reads the RECIST guidelines cover-to-cover quickly realizes that solid tumor interpretation is as much an art as science.

      I believe, however, that there is also another perspective.

      First, in a perfect world, we would only conduct 5 to 7 year double blind, randomized clinical trials based solely upon long term survival benefit as the endpoint. In an age of rapidly advancing science (e.g., discoveries regarding the functionality of VEGF, mTor, EGFR, ESR, p53, HER-2, HIF-1, VHL pathways, etc.) and technology (e.g., genome profiling, microarrays, bioinfomatics, etc.), we can expect drug treatment discoveries to rapidly advance, assuming that funding and patient trial participation is available. Assume for a moment that we use the HER-2+ breast cancer area as a high water mark. Once the discovery of Herceptin occurred, the drugs in that area rapidly went into preclinical and clinical testing. Many drug trials in that area did not make it to the 5 year point because superior short term survival advantage required researchers to discontinue the trial on ethical grounds so as to provide the novel agent to all women within the trial. The area of biopharmaceutical development will soon resemble “Moore’s Law” in the computer chip industry. So, the paradigm for long-term clinical trial testing with long term survival benefit as the sole endpoint is fading because in the time period it takes to obtain the data, a new and better drug has, or is about to, take its place.

      Second, for diseases such as ovarian cancer that are difficult to control (not initially, but ultimately) because they are diagnosed in late stage or become drug resistant, a breakthrough that leads to stable disease or partial response can ultimately lead to survival advantage. I believe that study findings indicate that stable disease for greater than 8 weeks (where the patient is asymptomatic or functions without Grade 3 or 4 adverse events) can be statistically indistinguishable from a so-called “partial response” in terms of survival benefit. And, it is possible for stable disease and partial response outcomes to translate into survival benefit. See e.g., Stabilization of disease as a useful predictor of survival following second-line chemotherapy in small cell lung cancer and ovarian cancer patients, and Is stabilization of disease a useful indicator for survival in second-line treatment of ovarian carcinoma pre-treated with Paclitaxel-Platinum?..

      Accordingly, if biotechnological developments continue to accelerate, it seems that the FDA and clinicians will have to become more comfortable with partial response and stable disease data in lieu of long-term survival data. In addition, I am a firm believer in the idea first conceived by the ancient Athenian orator and statesman Demosthenes that it is better to “live to fight another day.” After all, if you told me 5 to 7 years ago that a Stage IV HER-2+ breast cancer patient would have a superior survival advantage compared to a similarly situated Stage IV HER-2 negative breast cancer patient, I would say that you were crazy. But we know how that turned out! So, I think it is important for the regulatory agency and clinicians to stay open-minded in the future.

      As you said, let’s hope for a winner in the future — i.e., discover a “Herceptin equivalent” for the area of ovarian cancer or at least for one of the more genetically unique subtypes of ovarian cancer such as clear cell adenocarcinoma. Best, Paul

      Like

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s