CEL-SCI is now knocking at the door of the HPV – HIV/AIDS peri- anal warts treatment market
Enter CEL-SCI and the burgeoning market for the millions of men and women afflicted and suffering with the oral and genital manifestations of the HPV virus. Incredibly every day in the US alone, about 12,000 people ages 15 to 24 are infected with HPV.
New studies are now underway using CEL-SCI’s Multikine® as a treatment
·In February 2014, CEL-SCI announced the start of a Phase I study at the U.S. Naval Medical Center San Diego using the immunotherapy Multikine® (Leukocyte Interleukin, Injection) in HIV/HPV co-infected men and women with peri-anal warts. Dr. John Malone, Principle Investigator for the study, stated that “the immunologic agent Multikine® has potential to improve the clinical treatment of HPV lesions that are associated with cancer.”
·On July 20, 2015 CEL-SCI announced that it has added a second clinical site at the University of California San Francisco [UCSF] for its Phase I clinical trial evaluating peri-anal wart immunotherapy in HIV/HPV co-infected men and women with its investigational cancer immunotherapy Multikine®. Distinguished key opinion leader, Dr. Joel Palefsky** will serve as Principal Investigator at the site.
[Noteworthy is that CEL-SCI is also well underway with the world's largest Phase III study in head and neck cancer, underway at 87 clinical sites in 24 countries on three continents. The study was undertaken by CEL-SCI, with patient enrolment at 521 as of July 31, 2015 after new record patient enrollment of 33 in July. A total of 880 patients are expected to be enrolled, through approximately 100 clinical centers in about 25 countries by the end of March 2016.]
As I mentioned in my recent ON THE MARKET report on CEL-SCI:
“Can you imagine the degree of hard-eyed, in depth analysis that Dr. Palesky conducted before choosing CEL-SCI’s Multikine® to treat ‘this / his’ patient cohort in the just announced clinical trial? Obviously, he must have a ‘strong’ belief in the science surrounding Multikine® and have a really unwavering confidence that it will have good chance of bearing successful results with this group of patients. And likely he believes that he has the wherewithal to drive CEL-SCI’s Multikine® immunotherapy treatment solution to full enrolment in the trial. Finally it is highly unlikely, IMO, that Dr. Joel Palefsky would associate himself with a company about which he had any concerns or doubts.”
On reflection re my prior hypothesizing, let me add: I believe that it would be safe to say that, not only did Dr. Palefsky perform substantial due diligence on CEL-SCI, but that UCSF must have done plenty themselves prior to choosing CEL-SCI’s Multikine® as a treatment for anal warts in Phase I clinical trials.
For such a distinguished institution as UCSF, located at ground zero of one of the largest HIV and AIDS communities, to affiliate itself with a relatively small drug discovery company like CEL-SCI advocates enormously for the company and its technology. And when you think about it, the AIDS & HIV cohort, especially in San Francisco, is extremely advanced and knowledgeable re the disease and all its manifestations and treatments. Add in their substantial political clout that rings throughout the AIDS community and its institutional environs.
Evaluating the HPV complications and where opportunities lie for CEL-SCI
The incidence of the HPV infection and the subsequent genital warts manifestation is high in the general population, with approximately one million new cases annually and the incidence of genital warts increasing every year.The HPV subtypes 6 and 11 are the cause of over 90% of the exophytic anal warts.
Genital warts also have significant treatment costs. Depending on the extent and responsiveness of the warts to therapeutic intervention, treatment will require either many weeks of patient-applied therapy, several visits to the doctor's office for physician-applied therapy, or a surgical, electrosurgical, or laser procedure that may require hospitalization and anesthesia. The incubation period for genital warts varies from as little as 3 weeks to 6 to 8 months or more.
Anal HPV infections are more common than cervical HPV infections among HIV-infected women and anal cancer is an emerging cancer in HIV-infected men and women.
Disease progression from benign to malignant in the anal canal
The progression to cancer is much more common in immunosuppressed HIV-positive patients, indicating a significant increased risk of cancer development in this patient population. Undeniably, the realization that HIV leads to increased dysplasia has been in the literature for a quarter century.
The CDC says that each year in the USA about 33,000 new cases of cancer are found in parts of the body where human papillomavirus (HPV) is often found. HPV causes about 26,800 of these cancers. According to the World Health Organization, HPV was a cause of 90% of anal cancers – 40% of cancers of the external genitalia (vulva, vagina, and penis), and as alluded to above it’s the cause of 100% of cervical cancers.
Importantly,HPV is now the leading cause of oropharyngeal cancers, a space where CEL-SCI is well underway with the world’s largest head and neck cancer Phase III study.
A recent analysis from Kaiser-Permanente in California estimated the rate of anal cancer among the HIV-positive population to be 174/100,000 person-years -- and even higher among individuals with lower CD4+ counts -- compared to 2/100,000 person-years among the HIV-negative population. This rate is significantly higher than the rate of cervical cancer before Papanicolaou (PAP) screenings became routinely performed on women (35/100,000). Importantly the prevalence of anal cancer is rising as a consequence of increased longevity due to HAART.
Again, the incidence of anal cancer reported in these studies exceeds the highest reported incidence of cervical cancer anywhere in the world.
Peri-anal cancer treatment
According to The North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) the standard treatment for invasive anal cancer is a combination of chemotherapy and radiation therapy, which is associated with significant morbidity. The cost of clinician visits, hospitalization, diagnostic testing, drug treatments and therapeutic procedures is in the billions. Regrettably, anorectal surgical procedures are the most common operations performed in HIV-infected homosexual male patients.
In a review of 246 patients over 10-years at Stanford Medical School (Dr. Palefsky participated in this study), it was demonstrated that utilizing high-resolution anoscopy-directed biopsy and destruction with electrocautery of anal lesions, practitioners were able to clear 78% of patients of their high-grade squamous intraepithelial lesions. Notably 74% of their patients were HIV-positive and only 3 patients (1.2%) progressed to anal cancer. Nathan et al also showed that destruction of AIN lesions is quite feasible with a 63% cure rate at one year.
As in all cancers, generally speaking major progress is being made. In the 1980s, the 2-year survival for anal cancer was just 32%, by the mid-1990s it had risen to 54%, and by the end of the millennium it was 76%, which is comparable to that in the HIV-negative population.
Thus we see that the scenario of HPV morphing into oral and genital cancer in HIV and AIDS patients is a mammoth and growing worldwide problem.
Enter CEL-SCI and their investigational cancer immunotherapeutic agentMultikine® (Leukocyte Interleukin, Injection).
First the straightforward reason WHY the US Navy and UCSF are involved
The forthright premise re the use of Multikine® that the US Navy and now UCSF have chosen the drug as a treatment and the reason why they are allocating and spending significant resources in their Phase 1 trials:
The above-mentioned HPV / anal warts condition complicated by HIV / AIDS may well be effectively treated by CEL-SCI’s immunotherapy Multikine®. In immune system compromised patients, where the definition of their disease suggests degradation and depletion of the body’s natural response to disease (i.e. human immunodeficiency virus [HIV] and acquired immune or immuno- deficiency syndrome [AIDS]), the Multikine® investigational immunotherapy is directed at activating and possibly enhancing the body's immune response to help the body in addressing the HIV/AIDS disease complex. The patented Multikine® therapy could build, accelerate and facilitate new immune protection to increase the protective efficacy of the body’s cellular immune response, and accordingly, sustain the immunity with enhanced antibody production and protection.
In the UCSF and the Navy study Multikine® is being given to the HIV/HPV co-infected patients with peri-anal warts because promising early results were seen in another Institutional Review Board approved Multikine® Phase I study conducted at the University of Maryland. In this study, the investigational therapy Multikine® was given to HIV / HPV co-infected women with cervical dysplasia resulting in visual and histological evidence of clearance of lesions. In addition, elimination of a number of HPV strains was determined by in situ polymerase chain reaction [PCR] performed on tissue biopsy collected before and after Multikine® treatment. As reported by the study investigators; the study volunteers all appeared to tolerate the treatment with no reported serious adverse events related to Multikine®.
CEL-SCI believes that the disease indication being pursued by the U.S. Navy and now UCSF may also represent a relatively quick way to generate the necessary clinical data required to submit an application for marketing approval for Multikine®.
To date, CEL-SCI’s immunotherapy Multikine® treatment has completed Phase I and II clinical trials and is now over 50% through a global Phase III trial for advanced primary head and neck cancer.
* And then some
Tying up the HPV/anal/genital warts/HIV-AIDS/cancer interconnection and what it all means to CEL-SCI
Certainly, all bets are off when it comes to predicting results from clinical trials, (and let’s underline that) however - if the UCSF and Navy studies are favorable - more than considerable interest will suddenly manifest and build. Not only will it be hugely important news in the HIV / AIDS community, but the rational for other applications for the Multikine®investigational immunotherapyagent will surge, i.e. tumors and other infectious diseases.
Consider what Dr. Palefsky would mean even as a passive spokesperson (and I think he would be more than that.) The point here is that his affiliation with CEL-SCI’s Multikine®will drive enormous new Pharma interest in CEL-SCI and their immunotherapy treatment that the company would be unable to garner on their own. And keep in mind that results from these studies will be presented well before the data Phase III head and neck cancer study will be available.
I also believe that Dr. Palefsky knows a great-deal about Multikine® and its potential already. Certainly he didn’t commit his energies (and UCSF’s resources) without a vast amount of due diligence.
The mounting enrolments in the head and neck cancer study, the distinguished individuals and eminent institutions and entities involved, the exceptional Phase I results from University of Maryland (that if duplicated or even approximating) suggest a risk / reward metric heavily weighted to reward. With a market cap of only $60 million positive results will explode that number and the share price IMO.
** Dr. Joel Palefsky is a San Francisco-based, University of California [UCSF] physician, researcher, instructor, pioneer and specialist in the field of HIV / Aids and HPV. Doubtless, Dr. Palefsky—who has been at UCSF for over 25 years, and is the Chair of the HPV Working Group of the AIDS Malignancy Consortium [AMC], and is the head of the AMC HPV Virology Core Lab at UCSF as well as director of the UCSF Anal Neoplasia Clinic—knows the field as well as just about anyone. Notably, Dr. Palefsky was recently awarded an $89 million grant from the National Institutes of Health [NIH] where he is Principal Investigator of the ANCHOR study, the NIH-funded study of the efficacy of secondary prevention of anal cancer ongoing at 5 sites, and set to start in 7 other sites in the USA. Dr. Palefsky has published over 280 papers. The AMC is a U.S. National Cancer Institute-supported clinical trials group founded in 1995 to support innovative trials for AIDS-related cancers. Palefsky is the Principal Investigator on several laboratory-based and clinical research studies of HPV-associated neoplasia, particularly in the setting of HIV infection. He also specializes in the molecular biology and development of new treatments for HPV. Dr. Palefsky is the founder and immediate past president of the International Anal Neoplasia Society and is currently president of the International Human Papillomavirus Society. He is actively involved in training students in clinical and translational research. Dr. Palefsky has led the Doris Duke Charitable Foundation program at UCSF since its inception in 2001 and has been the leader of the Clinical Translational Science Awards TL1 program at UCSF since its inception in 2006. Dr. Palefsky has extensive experience in the biology of HPV infection, HPV infection in HIV-positive men and women, HPV vaccines, and in the design and implementation of multiple clinical research trials of HPV-related disease.
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