For more than thirty years, university immunologists and biochemists have referred to chemotherapy as a technique that in the future will be considered unrefined and barbaric. Although chemotherapy has blazed an early trail in medicine by treating a limited number of cancers with some success, as many as thirty years modernization is needed in medicine to meet current research and development laboratory standards. One problem with radiation and chemotherapy is that they create mutated cancer lines that are even harder to treat than the original cancer.
A number of social and economic factors contribute to the painfully slow advancement of cancer therapy evolution. Doctors seem poorly educated in laboratory science in spite of programs to introduce them to the process, lending to reluctance to try new approaches due to lack of understanding combined with insurance complications and the business needs of a practice to turn a profit.
Part of the reason stem cell therapies and complicated immunotherapies are especially are slow to catch on is due to the giant leap in scientific background required to understand their mechanism of action, which combined with insurmountable costs and FDA obstacles of designing clinical trials, is a lifetime of struggle for therapy developers.
As therapies evolve in the lab, FDA requirements of extensive preclinical and multiphasic clinical trials remain voraciously expensive and decades consuming while millions of patients suffer mortal consequences. According to the American Cancer society, cancer is the second leading cause of death with approximately 600, 000 people dying of cancer every year.
So why is chemotherapy failing so many millions of patients each year and yet still survives in modern medicine? Simply put, these drugs interrupt normal cellular processes in ways that often inhibit or disrupt cell division. That sounds good given that cancer is a disease caused by rapid cell division. Cancers deplete nutrients from reaching vital tissues and thus starving the afflicted person of processes necessary to survive. Sometimes partially treated cancerous cells become more resistant to further treatment after treatment by chemotherapy. But chemotherapy agents poison healthy cells as well, especially in vital tissues that are highly metabolic such as heart tissue. The problem may, however, not be the chemotherapeutic agent, but rather the delivery mechanisms of these agents.
Albert Einstein is quoted as saying that it is a miracle that science ever survived the academic system. We report here that the scientists at strong bio find it equally perplexing that science has survived the FDA. Many cancer patients, however, have not. For sake of simplicity, this essay will look at two major approaches to treatment of cancer that are undergoing late clinical trials or broken into product stages.
We will only mention in passing immunotherapies that flip switches within the signaling cascades of the immune system. We will not discuss micelle delivery systems or viral/gene therapies either, as they are completely different mechanisms of action for cancer treatment, but will here focus on drug delivery mechanisms that facilitate treatment of cancers called "linkers."
Veteran scientists are sore from decades of scratching their heads in amazement that the FDA has only recently begun to approve and favor cancer targeting therapies, some designed to activate an immune response to cancers. Understandably, immunotherapy takes time to develop antibodies and test in cancer indications and populations. One early example is an Anti-ctla-4 human antibody (Yervoy) developed at Cal Berkeley and Medarex about twenty years ago (now owned by Bristol-Myers Squibb Company (NYSE:BMY)) have proven safe and effective for some cancers and have been approved by the FDA albeit at a cost of hundreds of thousands of dollars per dose.
Going back to the mid 1980s, scientists reported immunolabeling t-antigens and other cancer specific moieties. What that means is that we have been able to target cancers specifically for about thirty years in the laboratory to tag, visualize, and study tumors. Most of these studies used antibodies that bind to surface molecules specific to cancer cells and not expressed in healthy tissues. But some chemotherapies can be used for this purpose as well, such as doxirubicin.
But cancer surface antigens can undergo a change of surface expression during treatment, or present other obstacles in heterologous cancer populations, and enable cancers to elude treatment efforts. Very recently, Immunomedics, Inc. (NASDAQ:IMMU) was given breakthrough status in February 2016 by the FDA for triple negative breast cancer, a 6.2 billion dollar indication, for sacituzumab govitecan (IMMU-132) with several other nice clinical product results in Phase 2 linking a cancer binding immunomolecule with a cancer treating medicine.
In fact, a whole group of such therapies are working their way to market but medicine still favors the toxic chemotherapeutic routes in many cases. However, the cost and speed of the FDA and science in developing immunotherapies is going to be a preclusive element in their development, even as a linker. We will be keeping an eye on the IMMU-132 progress through the FDA as an indicator of this process. The cost of treatment may prove to be preclusive to some populations around the world as well.
Many chemotherapies are still in use and are cost effective and can successfully treat some types of cancer in spite of their tendency to transform cancers into more malignant lines, or healthy cells into precancerous lines. So what is the next stage in the development of chemotherapy? Is there any hope for chemical technologies? When physicians use chemotherapy, they want to hit it hard and fast.
So increasing the specificity and delivery of anti-cancer agents would logically be the key to knocking a cancer out before it can transform or cause harm to the afflicted. Recent studies have looked at receptor-mediated endocytosis as a mechanism to target tumors specifically both for assay and for treatment. This is the normal process of all cells to take in growth factors in serum. Because cancer cells are growing and dividing rapidly, they take in larger amounts of serum relative to a quiescent or normal cell.
And alas after thirty years of waiting for a pivotal trial to test this mechanism, a very promising, relatively inexpensive, logical extension for physicians and the medical system has approached the point of data review. This linker/medicine conjugate is called aldoxirubicin, developed by CytRx (NASDAQ:CYTR) and works by binding both to doxirubicin (but can serve as a platform to bind any chemotherapy drug of interest) and to serum proteins in the blood post-injection. It does not use an antibody and therefore is not prone to some disadvantages of immunotherapy.
The treatment has met early but variable efficacy successes in Phase 1 and 2 trials for several cancer types: Kaposi's, glioblastoma, and soft tissue sarcoma, whereby it binds tumors preferentially to other healthy tissues. This treatment aldoxirubicin binds serum in the blood and releases doxirubicin impressively near to tumors in a pH dependent manner (cancers tend to run acidic), with early trials indicating much lower cardiotoxicity, a major risk factor of unlinked chemotherapies.
Interestingly, doctors have been allowed in this Phase 3 study to test extended dosing regimens for aldoxirubicin that were not used in Phase 2, to test whether or not higher dosages can knock out tumors hard and fast, and keep them down. Phase 3 pivotal data is to be published in July 2016. This trial will report the efficacy of aldoxirubicin as a monotherapy, and for a nice discussion of the trial conditions of comparison, I advise this article by another author.
But even with this promising therapy, CytRx, like IMMU, has been criticized for its conduct in promoting its therapies in order to raise money (or perhaps compete with others) for development of the technologies. These companies have had to try to raise money to develop their platforms for clinical trials with the FDA. Sometimes they can even involve the courts of law, although it appears as if CYTR has settled past lawsuits.
But a potential class action lawsuit for IMMU may be forming for announcing that they were going to present information from its clinical trials on triple negative breast cancer at the American Society of Clinical Oncology. But the company was not allowed to present this information at the last minute because it had already been presented in other venues, even though the company claimed a different statistical population of patients was represented, potentially violating a rule at ASCO. In any event, it never ceases to amaze us how many obstacles a technology company faces.
As another author from seeking alpha has noted, many biotechnology companies are forced to actively promote their results in order to raise awareness and the necessary funds required by the FDA to bring special advancements in technology to medicine. MEDX, IMMU, and CytRx are/were no such exceptions. For instance, Chief Commercial Officer Olivia Ware recently interviewed with Fox Business news in a TV interview and you can see her appear to be trying to hold back her excitement, but politely refrains from giving even basic information this close to the end of a Phase 3 trial.
In addition, principle investigator of the aldoxirubicin trial, Dr. Sant Chawla has also expressed his excitement for many oncologists overtly. In addition, unique to clinical development level biotechnology companies, CytRx has managed to secure 40 million in non-dilutive funds from Hercules Capital, with another non-dilutive 15 million if the pivotal Phase 3 data for aldoxirubicin meet FDA required endpoints spelled out in the special protocol assessment, all for a production facility. But there appears to be a fine line between promoting results and promoting legal sales of stock, which is not a focus here.
Evolution occurs in punctuated equilibria, not necessarily at a steady or predictable pace. Medicine and technology advance in a similar way. In order for cancer therapy to evolve, technology needs to proceed in digestible steps. Immunotherapies and stem cell therapies hold much promise, but may not be a digestible step for all of the roadblocks of advancement, and the cost might exceed necessary results in the end.
Aldoxirubicin may just BE living proof that the field of chemistry is not extinct, and the missing linker needed for physicians and oncology teams to target cancers specifically and expeditiously, and provide the necessary steps away from barbaric chemotherapy and segue into a refined future that would make Charles Darwin, Rudolph Virchow, and Robert Boyle proud.
Disclosure: I am/we are long BMY IMMU CYTR.
I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.
Additional disclosure: Please add as primary ticker for BMY, IMMU, CYTR