An increasing number of pharmaceutical companies in recent years have focused some or all of their research on rare and orphan diseases. Although these diseases have relatively small patient populations, and the research that goes into drug development can be quite costly, a success in developing a therapy to treat an unmet orphan disease can result in windfall profit and little to no competition for years for the developing company.

In addition to being good news for investors, a focus on orphan diseases in recent years is great news for people who suffer such rare afflictions. For those suffering from homozygous familial hypercholesterolemia, or HoFH, a rare hereditary disease that makes it difficult for the body to remove LDL cholesterol (the bad kind) from a person's blood, a possible third FDA-approved drug may be just around the corner.

An increased focus on HoFH
HoFH sufferers currently have two FDA-approved therapies to choose from that were approved just weeks apart in late December 2012 and January 2013. These are Juxtapid from Aegerion Pharmaceuticals' (NASDAQ:AEGR)and Kynamro from Sanofi (NASDAQ:SNY) and Isis Pharmaceuticals (NASDAQ:IONS).

Aegerion's Juxtapid has been the early standout despite an annual treatment price tag that is more than $119,000 higher than Kynamro. Juxtapid is a once-daily capsule taken in the evening well after a last meal; it works in conjunction with proper diet and exercise to remove LDL cholesterol from a patient's blood. While it did reduce LDL cholesterol levels by approximately half during the first 26 weeks of study in its phase 3 trial, it also comes with a boxed warning regarding liver toxicity: Juxtapid can cause the accumulation of fat in the liver, as well as liver enzyme abnormalities. The FDA's approval was given on the condition that Aegerion run three post-marketing studies regarding the safety of long-term use of the drug.  

Sanofi and Isis' Kynamro is an injection given to patients once a week that also works as an adjuvant therapy to proper diet and exercise to lower LDL cholesterol. Cholesterol levels for those taking the drug fell by a tamer 25% during the first 26 weeks. It, too, comes with a boxed warning due to the potential for liver toxicities associated with accumulation of fat in the liver and liver enzyme abnormalities. The drug-company duo was also required to run four post-marketing studies mainly to establish the long-term safety of the therapy. 

Meanwhile, select HoFH sufferers may soon have a new therapy to lean on if Amgen's (NASDAQ:AMGN) phase 3 studies continue to deliver primary endpoint-meeting results.

A wonder drug in the making?
The experimental therapy, which Forbes' health care columnist Matthew Herper said could become a direct competitor for about one-third of Juxtapid users, is evolocumab, known also as AMG 145.

Amgen's new therapy is unique in that it targets a protein known as PCSK9 which binds with LDL receptors and allows high levels of LDL cholesterol to persist in HoFH patients. However, a natural mutation of PCSK9 can actually cause a dramatic reduction in cholesterol in a patient which lowers the risk for cardiovascular disease. Amgen's evolocumab works by mimicking this mutation and inhibits PCSK9 from binding with LDL receptors, leaving more of those receptors free to remove LDL cholesterol from an HoFH patient's blood.

Earlier this week, Amgen released its latest findings in its TESLA phase 2/3 trial on evolocumab for HoFH. The first part of its phase 3 study met its primary endpoint of a clinically meaningful and statistically significant reduction in LDL cholesterol from baseline at week 12. Although specific data wasn't released, Amgen said it plans to release that information at an upcoming medical conference and through subsequent publications. Overall, Amgen's phase 3 program for evolocumab involves a whopping 14 separate trials that will evaluate its long-term safety and efficacy among a number of cholesterol-based diseases, including HoFH.

What's really intriguing about Amgen's therapy is that it's a subcutaneous injection given just once monthly for 12 weeks, then followed up with one injection every two weeks for another 12 weeks. Add that up and you're looking at just nine injections over 24 weeks, compared to 24 injections for Kynamro and 168 capsules for Juxtapid over the same time span.

Furthermore, in ongoing testing being done on evolocumab, the side effects have been incredibly mild relative to the boxed warnings of liver toxicity forJuxtapid and Kynamro. The TESLA trial noted that adverse events were balanced across treatment groups, with the most common being upper respiratory tract infections, influenza, gastroenteritis, and nasopharyngitis. In other words, evolocumab could possess a considerably better safety profile which may warrant preferential treatment from physicians if a patient is determined by genetic testing to be responsive to evolocumab.

Finally, as Herper pointed out in his discussion of evolocumab, because it targets high cholesterol, in general, through multiple trials and studies that will include around 30,000 people, if approved it'll have a huge market of potential patients. What that means for the consumer is a significantly lower annual price than Juxtapid or Kynamro, which are strictly geared toward a few select indications.

Wait and see
If everything continues to work in evolocumab's favor there's a strong chance that Amgen could file for a new drug application before the end of 2014. There's also a decent shot, since it would be for an orphan (or rare) disease, that the FDA could expedite the review process, possibly bringing a third FDA-approved drug to select HoFH patients before mid-2015.

Based on its impressive safety profile and pricing potential, evolocumab is certainly worth watching. I don't believe the experimental injection is a sure winner just yet, as I'd like to see the specific LDL cholesterol reductions the drug was capable of achieving in the TESLA trial -- but we should have that data soon enough. My suggestion would be to keep a close eye on the battle for improved efficacy in the HoFH arena, as Amgen may reap big profits and, more importantly, improved quality of life may await HoFH patients.