Twenty to 30 years ago, the conventional wisdom was that drug makers were only interesting in developing drugs for huge markets. That is, drugs treating chronic conditions that afflicted huge numbers of people. Think high cholesterol, hypertension, diabetes, allergies, etc. These drug therapies tended to cost $2 to $3 per day. In the past 15 to 20 years, drug makers shifted their focus to specialty drugs that affected far fewer people, like cancer and gene therapies, that sold for tens of thousands, if not hundreds of thousands of dollars per year. For reference, specialty drugs comprise only about 1% of drugs, but account for nearly half of drug expenditures. These tend to be biologics, drugs derived from living substances, that are much harder to copy once a patent has expired. Biologics are large molecule, compared to small molecule drugs that often come in pill form. Most drugs on the market are small molecule drugs that can easily enter cells due to their small molecular size.
Earlier this year I wrote about bacteriophages, naturally-occurring antibiotics that are not widely available. Phases, as they’re called, are viruses found in nature that kill bacteria. Each is highly specific, killing only one kind of bacteria. That is (possibly) why pharmaceutical companies haven’t shown a lot of interest in developing them as antibiotic drug therapies. Drug companies would need to develop a different bacteriophage therapy for each pathogen targeted. Although mostly ignored by Western drug companies, phages were common in former Soviet-bloc countries. The following is an article about a rare, drug-resistant bacteria that affected Gulf War soldiers treatable only by phages.
Most people probably don’t realize that bacteria are territorial, expanding where they can and defending their territory from other invaders. For instance, lactic acid bacteria inhibit the growth of other bacteria by producing an acid. These are used in yogurt and cheese making to preserve dairy proteins. Fun fact: another microbiological invader is penicillin, a fungus discovered in 1928. It was the first commercially available antibiotic. Its purpose in medicine is to kill bacterial infections. Purportedly the first commercially viable strain came from a moldy cantaloupe at a Peoria, Illinois market in 1942.
There are other types of potential drugs that are ignored for various reasons. One that is not very common is peptides.
Peptides have been traditionally considered bad candidates for the development of drugs due to some of their pharmacokinetic properties. However, using peptides in drug development is an increasingly popular option.
Your body produces peptides for a range of purposes (skin, bone, muscle, cartilage, joints, etc.) but peptide production slows down with age. According to the National Human Genome Institute:
A peptide is a short chain of amino acids (typically 2 to 50) linked by chemical bonds (called peptide bonds). A longer chain of linked amino acids (51 or more) is a polypeptide. The proteins manufactured inside cells are made from one or more polypeptides.
Peptide therapy is probably most commonly associated with anti-aging. As I’ve said in the past, the U.S. Food and Drug Administration (FDA) does not consider aging a disease, making it harder to get a drug approved that slows a common human condition. A passage from WebMD describes more about the use of peptides:
Studies have also found that certain types may have benefits for your skin, muscles, and maybe your weight. So companies are putting them into skin products and dietary supplements you can buy over the counter.
Peptides are also used to create drugs to treat a variety of diseases. More than 100 peptide drugs are available in the U.S. They’re used to treat conditions like type 2 diabetes, multiple sclerosis, and high blood pressure. And more are coming out all the time.
Indeed, there is an academic journal, called Peptides. According to an article in Frontiers in Chemistry, part of the reason there is not more interest in peptide drugs is (despite all the protein drink supplements on the Internet) they do not lend themselves to oral absorption.
Finally, oral bioavailability (in fact the lack thereof) is a constant discussion topic between peptide drug developers and pharma. Peptides can rarely be absorbed by the intestinal mucosa, and thus cannot serve the appealing lifestyle drug market that includes treatments for weight-loss, smoking, erectile dysfunction, wrinkles, and baldness (Atkinson, 2002).
What that means is that peptides are mostly administered by an injection, rather than a pill. To mimic the body’s peptide production, they need to be given daily if not more than once daily. Imagine picking up a monthly prescription for three different peptides, consisting of 300 pre-loaded syringes. Peptides are also more expensive to produce than small molecule oral tablets.
On the other hand, peptides are highly specific and bind tightly to their targets. Since they mimic natural peptides produced by the body they’re low in toxicity. Much of the research on peptides centers on how to improve oral bioavailability of peptide therapies.
The following is worth reading, Current Challenges in Peptide-Based Drug Discovery.