CEL-SCI Corporation (NYSE American: CVM) today issued a letter to its shareholders.
Dear CEL-SCI Shareholders:
We all know people who have been diagnosed with cancer. Some were deemed to be curable, while others were not. Our goal with our Multikine* (Leukocyte Interleukin, Injection) immunotherapy treatment is to increase the success rate of a cancer patient's first treatment. We want to help cancer patients live significantly longer and potentially increase their chances of being cured. And we want to do so with minimal to no toxicity from our Multikine immunotherapy treatment regimen. That is a huge goal, and that is why we have never given up during its long development. If proven to work for head and neck cancer, a truly horrible disease, we believe that our unique Multikine immunotherapy will prove to be useful for a number of other solid tumors including breast cancer, cervical cancer, melanoma, and more.
The usual oncology drug development paradigm is to test a drug for its effectiveness in recurrent cancer patients, those whose tumors have come back after the initial standard of care (SOC) treatments failed. That makes business sense since the drug being developed gets to market faster with less money at risk. But this paradigm makes no sense with our Multikine immunotherapy treatment because the first cancer treatments cause profound damage to our immune system. Our Multikine treatment regimen has been shown to act by stimulating a sustainable anti-tumor immune response to fight the cancer. Therefore, in order to maximize the benefit of immunotherapy for patients, we feel it is only logical that Multikine should be given as the first treatment, before surgery, radiation and chemotherapy have damaged the immune system, since that is the time when the immune system is still intact. This approach, using an immunotherapy right after cancer diagnosis and before surgery, makes Multikine unique and a first in a new class of drugs.
The first patients we targeted in our Multikine development program were those with advanced (stages 3 and 4) primary (just diagnosed and not yet treated) squamous cell carcinoma (cancer) of the head and neck. This patient population was chosen for the following reasons:
- Head and neck cancer affects a large number (>650,000) of people worldwide.
- It is an extremely devastating and debilitating disease that is highly visible, and can interfere with eating, speaking, swallowing, and breathing.
- Patients with this disease have an extreme unmet medical need as no products have been approved by the FDA for this patient population in over 50 years.
- We have FDA orphan drug status for Multikine in this disease.
- There is only one standard of care (SOC) treatment for this disease.
The current SOC for advanced primary head and neck cancer patients is surgery followed by radiation or surgery followed by radiation and concurrent chemotherapy. This treatment regimen is given with "intent to cure" (that is what the medical community calls this current SOC treatment), yet typically no more than 50% of the patients will be alive at 3 years post diagnosis. We need to and must do much better for these patients.
The recurrences that occur in head and neck cancer patients treated with the current SOC therapy are thought to be mostly due to tumor micro-metastases that the surgeon cannot see, and thus cannot remove, and that radiation and chemotherapy do not manage to kill. We believe that only a healthy immune system, correctly activated, can find and destroy these tumor micro-metastases before they cause recurrence of the cancer. We want to make the current "intent to cure" cancer treatment more successful by having our Multikine immunotherapy treatment regimen activate the immune system to kill the tumor micro-metastases.
We reached the end of our pivotal Phase 3 study in head and neck cancer in April 2020. The Clinical Research Organizations (CROs) running the study are now involved in the study phase of performing data lock/analysis.
If our Phase 3 study is successful, the results would truly be revolutionary, demonstrating a new way of treating cancer. The study was designed to prove this novel concept and maximize our chances of proving success. We took no shortcuts and addressed the major concerns of the scientific community:
- The study is well-controlled and the outcomes are blinded to us until the end.
- The study was run as a real-world representation of the disease in 100 centers in over 20 countries.
- In addition to Overall Survival (OS) as the primary endpoint for the study there are several secondary endpoints which are indicative of meaningful clinical benefit.
- The number of patients (928) in the study is large enough to yield significant results, and the duration (9 years and 4 months) long enough to provide reliable results assessing response/outcome duration. To our knowledge, our Phase 3 study is the largest ever done in advanced primary head and neck cancer.
- We purchased the cisplatin chemotherapy, used as part of the SOC treatment, only from manufacturers meeting U.S. and EU standards, and distributed it to all clinical sites. We did so to ensure that all study patients received the same chemotherapy drug, thus avoiding the use of cisplatin with different quality levels, which might have caused variation in results following treatment.
- We standardized and controlled the radiotherapy given by each clinical site in our study with the help of the radiation quality control group at MD Anderson - a group which also controls radiotherapy in studies conducted by major pharma and government groups in the U.S. and Europe.
- We built a dedicated commercial sized manufacturing plant for Multikine prior to the start of the Phase 3 study to eliminate important regulatory hurdles pertaining to manufacturing. All of the Multikine lots used in the Phase 3 clinical study were manufactured in this facility.
We also met with the FDA before starting the Phase 3 study. All suggestions made by the FDA were incorporated into the Phase 3 protocol:
- We agreed to make the primary study endpoint Overall Survival, the gold standard for cancer drug approval.
- We agreed to add a third study group.
- The plans for our Multikine manufacturing plant were reviewed by the FDA prior to its construction. All suggestions made by the FDA with respect to design were incorporated into the plant when constructed.
- The plant was inspected on several occasions by a European Qualified Person prior to and during the Phase 3 clinical trial to assure compliance with the EU directives for the manufacture of medicinal products.
- The European Qualified Person also released all of the Multikine lots for use in the EU countries in compliance with EU Directives.
Early this year we took one more step to ensure the completeness, accuracy, and validity of the study data. We tasked a group of physicians from Ergomed and ICON, the two CROs managing the Phase 3 study, to perform a 100% medical review of all of the study patients. That is akin to doing a 100% audit of all of the medical results.
In early May 2020 we announced that we had reached the required 298 events (deaths) among the two main comparator groups, signifying the end of the Phase 3 study. We announced that the two CROs would be performing data lock and the complete data analysis. Only when the complete analysis has been concluded according to a pre-specified statistical analysis plan, will CEL-SCI become privy to the study results. Per SEC regulations we will then notify you, our shareholders, of the results at that time.
Data lock is a complex, in-depth, and time intensive review process of all of the study data from beginning to end to ensure it is complete and accurate. This process is even more complicated for our Phase 3 study because it involved three treatment arms as well as four treatment modalities, Multikine, surgery, radiation, and chemotherapy.
To be used in support of a FDA license application or a product registration anywhere in the world, every data point in each patient's case report form concerned with, among other things, their selection, randomization, laboratory assessments, safety and efficacy evaluations of all treatment(s) received must be reviewed, and the source data verified as complete, accurate and correct. Since the data from our study will most likely be audited by regulatory authorities prior to any license or approval being granted, the data lock procedures must be completed with extreme care before the data base can finally be locked and a complete analysis of the study results can be performed. The analysis will evaluate the safety of the Multikine treatment regimen and determine if the primary, secondary and tertiary study endpoints of the Phase 3 study have been met.
The length of time it takes to lock data from a study and analyze it depends on the size and complexity of the study, the number of study sites and personnel involved, and the period of time over which the study was conducted. Our Phase 3 study was very complex and was conducted in 928 patients over the course of 9.5 years in 100 medical centers on 3 continents. The CROs have to review a lot more data for our study than in most other studies, which are not as large, not as complex or geographically dispersed, and did not run for such a long period of time.
The COVID-19 pandemic has complicated and delayed the data lock process for our Phase 3 study and added to our workload. Direct access to the source data at the clinical sites has sometimes been limited due to the pandemic by governments, institutions and the availability of the study personnel required to respond to any matters/queries requiring resolution. In some cases, and in compliance with guidance issued by the FDA and other regulatory bodies, it has been possible to perform remote data reviews and source data verification, but not in all. From what we can see the CROs are doing a good job, but everything takes longer as a consequence of the COVID-19 pandemic. The bottom line is that we have highly skilled professionals around the world working to resolve this, and they are getting it done. We are almost at the end!
Should the results of our Phase 3 study confirm that our Multikine immunotherapy treatment regimen provides a meaningful clinical benefit for the patients in our Phase 3 trial, as we saw in our final Phase 2 Multikine clinical trial, we expect to file a license application for Multikine with the FDA for its use as a neoadjuvant (pre-surgery) treatment in advanced primary head and neck cancer patients. If approved, this license would allow us to commercially distribute Multikine for this indication. Given the fact that advanced primary head and neck cancer is a clear unmet medical need with no FDA approval in well over 50 years and that Multikine appears to be safe and well tolerated based on the data available from all of our previous clinical trials, we would be surprised if such a license were not granted. We are currently expanding our Multikine manufacturing facility in Maryland so we will be able to meet the expected demand for the product when a license is granted.
Come December 31, we want to be able to look back on the year and know that, in spite of the COVID issues and delays, we did not take shortcuts and we did everything right. We believe that we have a "really good shot" at creating a truly novel cancer drug that seeks to help cancer patients live significantly longer and potentially increase their chances of a cure. And we also believe that we will be able to do so with minimal to no added toxicity from our Multikine immunotherapy.
We thank you very much for all your help and support as we eagerly await the final data read-out from our Phase 3 cancer study.
Geert KerstenChief Executive Officer
This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, including statements with respect to Multikine and the Phase 3 clinical trial of Multikine in patients with advanced primary squamous cell carcinoma of the head and neck. When used in this press release, the words "intends," "believes," "anticipated," "plans" and "expects," and similar expressions, are intended to identify forward-looking statements. Such statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected. Factors that could cause or contribute to such differences include an inability to duplicate the clinical results demonstrated in clinical trials or nonclinical studies, timely development of any potential products that can be shown to be safe and effective, receiving necessary regulatory approvals, difficulties in manufacturing any of the Company's potential products, inability to raise the necessary capital and the risk factors set forth from time to time in CEL-SCI's filings with the Securities and Exchange Commission, including but not limited to its amended report on Form 10-K/A for the year ended September 30, 2019. The Company undertakes no obligation to publicly release the result of any revision to these forward-looking statements which may be made to reflect the events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.
* Multikine (Leukocyte Interleukin, Injection) is the trademark that CEL-SCI has registered for this investigational therapy, and this proprietary name is subject to FDA review in connection with the Company's future anticipated regulatory submission for approval. Multikine has not been licensed or approved for sale, barter or exchange by the FDA or any other regulatory agency. Similarly, its safety or efficacy has not been established for any use. Moreover, no definitive conclusions can be drawn from the early-phase, clinical-trials data involving the investigational therapy Multikine. Further research is required, and early-phase clinical trial results must be confirmed in the Phase 3 clinical trial of this investigational therapy that is in progress.
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