US Phase II Trial Results For PVAC
Genesis, Corixa And Medicis Announce US Phase II Trial Results For PVAC™
Evidence Of Clinical Benefit And Safety At 15-Microgram Dose
Auckland, NZ, Seattle, WA, and Scottsdale, AZ, Feb. 15, 2001 — Biotechnology company, Genesis Research and Development Corporation (NZSE/ASX: GEN), together with its U.S. partners, Corixa Corporation and Medicis Pharmaceutical Corporation today announced preliminary U.S. Phase II clinical trial results on their immunotherapeutic psoriasis treatment, PVAC™. Analysis of the results of a four-arm, randomised, double-blinded, controlled study in the United States, suggests that PVAC therapy at a dose of 15 micrograms per injection provides appreciable clinical benefit in patients with moderate to severe psoriasis.
Enrollment of 241 patients in the Phase II PVAC treatment study in the USA was completed in August 2000. In this four-arm study, patients with moderate to severe psoriasis were randomised to one of four groups. Individual groups (approximately 60 patients) were then treated with either control (CANDIN, a local irritant which produces a hypersensitivity reaction in most patients) or one of three different dosages of PVAC treatment (2, 15 or 50 micrograms). Efficacy endpoints – improvements in disease severity as assessed by decrease in psoriasis area and severity index (PASI) score – were measured every three weeks for twelve weeks following the first administration of study treatment. In this Phase II trial, PVAC or control were given via intradermal injection on day 0 and day 21 of the study. This was the same route of administration and dosing schedule that was used in early Phase I PVAC studies conducted in the Philippines.
Evidence of Clinical
The Phase II study, conducted in a randomised and controlled setting, was designed to provide safety data and to determine an optimal dose for future efficacy studies. However, clinical efficacy assessed in the middle dose group (15 micrograms), as compared to the CANDIN control group, approached statistical significance (p=.08) when the efficacy endpoint was at least a 50 percent reduction in PASI score. The companies have concluded that patients receiving the 15-microgram dose had more impressive results than patients receiving other doses. Among the 60 patients in the 15-microgram-dose group, 23 percent had a 50 percent or greater reduction in PASI score at 12 weeks.
Of the 21 patients in this dose group who had not been treated previously with any form of ultraviolet light, methotrexate or cyclosporin, 43 percent had a 50 percent or greater reduction in PASI score at 12 weeks. Methotrexate, cyclosporin and ultraviolet light therapies are modalities reserved for the most serious cases of psoriasis and likely affect the immune system for long time periods and perhaps permanently. The vast majority of psoriasis patients are not treated with these agents, according to a survey of physicians conducted by Market Measures, Inc. The 15-microgram dose was the same dose administered in Phase I PVAC treatment trials conducted in the Philippines that had previously suggested clinical benefit.
Moreover, further analysis indicates that the percentage of responders in the 15-microgram-dose group achieving either a 50 percent or 75 percent reduction in PASI score continued to increase with time and reached their highest levels at the 12 week observation point. The companies believe this observed increase in efficacy over time suggests that more patients might have been found to reach either a 50 percent or 75 percent improvement in disease severity had the observation point been later than 12 weeks from the first dose of PVAC. A later observation point was not measured because of the Phase II study design. Subsequent studies will likely include measurement points beyond 12 weeks.
Detailed analyses of patient responses at the 15-microgram dose confirmed the clinical efficacy of PVAC. For example, when a comparison was made of the best response (decrease in PASI score) observed at any observation point for patients in the 15-microgram-dose group was compared to the best response in the CANDIN control group, a statistically significant difference was observed favouring the 15-microgram dose group (p= 0.04).
In addition, the moderate and severe psoriasis patients treated in the U.S. Phase II trial had a significantly longer prior history of disease (median of 18 or more years) than did patients treated in the initial Phase I Philippines study (median of three years prior disease history). Moreover, the U.S. patient population studied in the Phase II trial had significant prior exposure to a variety of therapies for a duration that might interfere with or delay responses to an immunoregulatory product such as PVAC, including repetitive exposure to immunosuppressive therapies such as ultraviolet light irradiation, methotrexate and cylcosporin. As such, the U.S. Phase II study provided an extremely rigorous test in which to assess the clinical performance of PVAC.
The benign safety profile of PVAC observed in Phase I investigation was again confirmed in the U.S. Phase II clinical trial. There were no moderate or severe systemic adverse reactions to PVAC administration, nor were there any differences in frequency of other systemic adverse events observed between any PVAC dose group, or between any PVAC dose group and the control group. The only adverse event with an increased incidence over the control group was the percentage of patients with injection site reactions in the 15- and 50-microgram dose groups compared to the site reactions induced by CANDIN. The majority of injection site reactions were mild to moderate.
“Based on the preliminary data disclosed today, we are quite encouraged that PVAC treatment continues to demonstrate clinical benefit in a controlled setting,” said Steven Gillis, Ph.D., chairman and chief executive officer of Corixa. “The U.S. Phase II study has demonstrated clinical activity at the same dose of 15 micrograms per injection that was evaluated in the Philippines. Corixa and its partners, Medicis, Genesis Research and Development, and Zenyaku Kogyo, are developing plans for the next major clinical study of PVAC. Such a trial will likely be a randomized, blinded and controlled study in which different groups of patients would receive 15 micrograms of PVAC in possibly two or three different dosing schedules. Based on the results to date, clinical benefit may be assessed at multiple time points following administration for a longer period of time. Studies may also compare patients with different prior exposure to immunosuppressive therapy.
Gillis added, “Given the speed with which the current study was accrued and completed, we are hoping to construct a statistical plan very shortly for the next study that the FDA may consider supportive for product registration. In the interim, we will gather additional data from an on-going 180 patient, randomized study in Brazil. In this trial of moderate and severe psoriasis patients, patients are being randomized to two-dose therapy with either saline, or 15 or 50 micrograms of PVAC treatment.”
Jonah Shacknai, chairman and chief executive officer of Medicis added, “We are very encouraged by the results of this Phase II study. We have improved greatly our understanding of PVAC’s appropriate dosing regimen, the objective of this phase of development. We believe PVAC demonstrated an impressive effect on some of the toughest psoriasis cases, with a clear reinforcement of the agent’s attractive safety profile. If further trials continue to show strong efficacy and safety results, we believe that we that will have an excellent commercial platform for PVAC.”
“We are heartened by the consistent safety profile displayed by PVAC treatment and the strong parallels in the dose regimen and efficacy that have come from the Philippines and U.S. Phase II studies,” said Jim Watson, chief executive of Genesis. “If our ongoing and further studies continue to show strong efficacy results, we believe PVAC has every prospect of being an excellent first-line therapeutic for psoriasis.”
On August 19, 1999, Genesis and Corixa announced a multi-year license, research and development agreement with Zenyaku Kogyo Co. Ltd., providing the company with exclusive rights to PVAC in Japan. On August 15, 2000, Genesis and Corixa announced a multi-year development, commercialisation and license agreement with Medicis for the commercialisation of PVAC in the United States and Canada. PVAC treatment is a derivative of Mycobacterium vaccae (M.vaccae) developed by Genesis in collaboration with Corixa.
According to the US National Psoriasis Foundation, psoriasis is a chronic skin disease affecting more than seven million Americans, or about 2.6 percent of the U.S. population. Psoriasis occurs when new skin cells grow too rapidly, resulting in inflamed, scaly skin lesions. It is estimated that approximately 30 percent of the patient population suffer from a moderate to severe form of the disease. About 150,000 to 260,000 new cases of psoriasis are diagnosed each year. Annual outpatient costs for treating psoriasis are currently estimated at approximately US$1.6 to US$3.2 billion. Although the cause of psoriasis is unknown, researchers believe the increased activation, adhesion and passage of T-cells to the skin contributes to the inflammation and abnormal skin cell proliferation. Most current psoriasis therapies are palliative in nature and provide temporary patient benefit, or have significant side effects.
Genesis is a New Zealand-based biotechnology committed to the building of a broad genomic platform for the development of innovative products for human health and agriculture. Genesis uses partnerships with industry leaders to target products that have global market potential through the gene mining of its extensive microbe, plant and mammalian EST databases. In addition to its collaboration with Corixa in the development of PVAC, Genesis has two other programs in human clinical development, five additional programs in pre-clinical development and two programs in plant biotechnology. Genesis was founded in 1994 in Auckland, New Zealand. For more information, please visit the Genesis website at www.genesis.co.nz.
Corixa is a research- and development-based biotechnology company committed to treating and preventing autoimmune diseases, cancer and infectious diseases by understanding and directing the immune system. Corixa is focused on immunotherapeutic products and has a broad technology platform enabling both fully integrated vaccine design and the use of its separate, proprietary vaccine components on a standalone basis. Corixa currently has 16 programs in clinical development and 22 programs in preclinical development, including its most advanced product candidate, Bexxar™, a monoclonal antibody conjugated to a radioisotope.
The company partners with numerous developers and marketers of pharmaceuticals and diagnostics, targeting products that are Powered by Corixa™ technology with the goal of making its potential products available to patients around the world. Corixa was founded in 1994 and is headquartered in Seattle, Wash., with additional operations in Hamilton, Mont. and Redwood City, Calif. and South San Francisco, Calif. For more information, please visit Corixa's website at www.corixa.com or call the company's investor relations information line at 1.877.4CORIXA or 1.877.426.7492.
Medicis is the leading independent pharmaceutical company in the United States focusing primarily on the treatment of dermatological conditions. Medicis develops and markets leading products for major segments within dermatology including acne, fungal infections, psoriasis, eczema, rosacea, seborrheic dermatitis, head lice and cosmesis (improvement in the texture and appearance of skin). Primary products include the prescription brands DYNACIN® (minocycline HCl), TRIAZ® (benzoyl peroxide), LUSTRA® (hydroquinone), LOPROX® (ciclopirox), OVIDE® (malathion), PLEXION™ (sodium sulfacetamide/sulfur), LIDEX® (fluocinonide), SYNALAR® (fluocinolone acetonide), TOPICORT® (desoximetasone), NOVACET® (sodium sulfacetamide/sulfur) and A/T/S® (erythromycin); the over-the-counter brand ESOTERICA®; and BUPHENYL™ (sodium phenylbutyrate), a prescription product indicated in the treatment of Urea Cycle Disorder. Full prescribing information for any Medicis prescription product is available by contacting the Company.
NOTE: CANDIN is a Candida albicans skin test antigen manufactured by Allermed Laboratories Inc., San Diego, CA.
GENESIS, CORIXA AND MEDICIS ANNOUNCE US PHASE
II TRIAL RESULTS FOR PVAC™
A MEDIA CONFERENCE WILL BE HELD AT 1.00PM TODAY AT TO DISCUSS THE RESULT GENESIS’ OFFICES AT 1 FOX STREET, PARNELL AUCKLAND.
1. Genesis Research and Development Corporation
and its US partners, Corixa Corporation and Medicis
Pharmaceutical Corporation have provided preliminary results
from U.S. clinical trials of their PVAC™ treatment for
2. 241 patients with moderate to severe psoriasis were treated with either a control or one of three different dosages of PVAC (2, 15 or 50 micrograms)
3. The results suggest that PVAC therapy at a dose of 15 micrograms per injection provides appreciable clinical benefit in patients with moderate to severe psoriasis.
4. PVAC’s safety is outstanding. There were no moderate or severe systemic adverse reactions to administration of the treatment.
5. The research profile follows the response pattern seen in Phase I trials of PVAC conducted earlier in the Philippines
6. The effective dosage is low (15 micrograms) and falls within a narrow band
7. Patients that respond best are those with moderate to severe symptoms
8. After participating in the trial for 12 weeks all patients became eligible to receive two more injections of openly labelled PVAC at the 50 microgram dose.
9. Efficacy continued to increase over the 12 week period of the study
10. This suggests that more patients might improved had the trials been continued for longer than 12 weeks.
11. Patients who had not previously been on immunosuppressive treatments (such as methotrexate or cyclosporin) responded best to the treatment.
12. Genesis and its partners are developing plans for the next major clinical study of PVAC which is likely to involve administering a 15 miocrogram dose on different schedules and assessing clinical benefits over a longer period.
13. Psoriasis is a flaky skin disease that affects 2% - 3% of the population worldwide
Editors please note: for a more complete discussion of the preliminary results, please read the full media release that accompanies this summary