We’re midway through the year, and the U.S. Food and Drug Administration (FDA) has already approved just shy of 50 new drugs. The second half of the year, however, promises to be just as interesting as the first.
A number of pharmaceutical, biotech and other medical companies are set to kick off pivotal trials in their efforts to bring a drug to market that has the potential to be a game-changer in its target indication.
Which is why investors need to be on the watch.
Trial successes and treatment approvals are rocket fuel for the companies behind them. Especially when it comes to biotechs and pharma firms with just a handful of prospective drugs (or especially just one), good news can light shares ablaze, quickly delivering double-digit gains and even doublers depending on the significance of the latest results.
Here are three drugs to watch — and the companies behind them — that are each set to move into a pivotal study near-term.
Drugs to Watch: Givosiran
Company: Alnylam Pharmaceuticals
Target: Acute Hepatic Porphyrias (AHP).
Givosiran, by Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY), treats an indication of what’s called acute hepatic porphyrias (AHP). Chances are that many reading are unfamiliar with AHP, and that can be forgiven — it’s an ultra-rare condition that affects somewhere in the region of 5 out of every 100,000 individuals in the U.S. and Europe.
This doesn’t make it worthless as a target population, however.
The FDA set up the Orphan Drug Designation system to incentivize the development of drugs for conditions exactly like this one, with companies not only set to draw benefit from various designation-associated perks but also from the ability to charge a premium price tag if and when the drug hits shelves.
AHP is one of a family of conditions called the porphyrias, each of which is predominantly caused by a genetic mutation in one of the eight enzymes responsible for heme biosynthesis (a heme is the nonprotein part of hemoglobin that contains the iron). It’s a pretty complicated condition, but more simply put: The fact that the hemes aren’t getting synthesized results in a number of the construction inputs of these hemes building up in the body. This buildup is toxic and results in attacks, characterized by abdominal pain, which can in some instances be fatal.
Givosiran works by inhibiting an enzyme called ALAS1, which is responsible for kick-starting the process of heme synthesis.
The drug has performed promisingly in a bunch of early to mid-stage trials, and Alnylam is set to build on these early data with a pivotal Phase III study this year. The trial will likely follow a similar protocol to the Phase II that preceded it, in that it will seek to demonstrate the silencing of the above-mentioned enzyme (ALAS1) as a sort of surrogate, biomarker type endpoint and, in parallel, try to demonstrate the lowering of two key inputs — aminolevulinic acid (ALA) and porphobilinogen (PBG), both of which are toxic heme intermediates that cause the attacks associated with the condition.
This one is set to kick off during late 2017 and, based on previous investigations, should run for 12 months once enrollment completes. Bear in mind that enrollment in this sort of ultra-rare condition can be slow (as patients are difficult to come across). Thus, enrollment completion becomes a major catalyst, alongside the more standard trial completion and data readouts.
Drugs to Watch: BMN 270
Company: BioMarin Pharmaceutical
This one is a little less complicated and has a much wider target population. The drug is called BMN 270, and as might be expected from BioMarin Pharmaceutical Inc. (NASDAQ:BMRN) — king of blood drugs — it’s being developed as a potential therapy for patients that have a deficiency of what’s called Factor VIII, a blood-clotting factor.
In healthy patients, Factor VIII is produced in the liver and circulates in the blood in an inactive form, bound to what’s colorfully called the von Willebrand factor, a glycoprotein named after its discoverer. When an individual suffers a wound that causes them to bleed, Factor VIII disconnects from the von Willebrand factor and binds to what’s called Factor XI — another factor key to the blood clotting process. Once the VIII and XI Factors bind together, a process starts that results in coagulation and, by proxy, clotting at the site of the bleed.
Nothing is available to bind to Factor XI in patients with a Factor VIII deficiency, and this translates to an inability to effectively form blood clots. In turn, this results in the condition known as hemophilia, where patients can bleed profusely (and very dangerously) from small cuts.
Standard of care therapies in this space basically revolve around trying to introduce blood clotting agents into a patient through ongoing therapy (one of which is set up to introduce Factor VIII to varying degrees), but the necessity for chronic administration and the overarching lack of long-term efficacy mean there’s a distinct unmet need for another therapy type to hit shelves.
BMN 270 is a gene therapy drug designed to replace the faulty gene responsible for the lack of sufficient Factor VIII production with a sort of synthetic alternative. The replacement gene performs the function that the faulty one should, coding for the VIII protein and overcoming the deficiency. With an approach like this, the treatment targets the underlying cause of the condition as opposed to just trying to pump a patient full of clotting agents, meaning (if it works) BioMarin could be set to pull in a large portion of the hemophilia market on approval.
This one’s a pivotal trial, but it’s a Phase IIb as opposed to a Phase III, and data from earlier stage studies have demonstrated to the agency in the US that the phase IIb will be enough to underpin registration (assuming BioMarin can replicate the numbers as part of an expanded population).
BMRN is already well underway with construction of the manufacturing facility that’s going to create the study drug. It expects to initiate the trial during Q3 2017.
Drugs to Watch: Sci-B-Vac
Company: VBI Vaccines
Closing out the list is VBI Vaccines Inc. (NASDAQ:VBIV) with its asset, Sci-B-Vac. This hepatitis B vaccine is already approved in a number of global markets but has yet to earn regulatory green lights in the three major markets for this sort of preventative vaccine-type asset — the U.S., Canada and Europe.
Just as with BioMarin’s asset, the science behind the mechanism of action is pretty neat. In their current form, there are two generations of vaccines.
The first introduces a bit of a virus (usually deactivated to a degree for safety reasons) to the immune system, with the goal of inducing the creation of antibodies specific to the virus in question. These antibodies then lay dormant until a live infection happens, at which point they are already in place to overcome the infection.
The second uses an antigen, which is the part of a virus that the immune system recognizes as foreign and introduces only this antigen to the patient’s system (usually in combination with some sort of adjuvant). This is much safer than adding live (even deactivated) virus to a patient’s body as there’s basically no risk of infection. But it has drawbacks in the sense that it is sometimes unable to induce an immune response sufficient to be classed as seroprotection. Many of the current standard of care vaccines in hepatitis B, including GlaxoSmithKline plc (ADR)’s (NYSE:GSK) Engerix-B (which is perhaps the most well known of the bunch) is a second generation type vaccine.
The third generation, of which Sci-B-Vac is one, is similar to the second in that it uses antigens to stimulate antibody creation. It differs in that it presents two or more antigens to the immune system as opposed to just one. In the case of Sci-B-Vac, the vaccine contains three antigens associated with the HBV virus — the one that second generation vaccines use and two others that have yet to be used in commercial vaccination.
The extra antigens should translate to an improved rate of seroprotection and a quicker time to effectiveness. Additionally, it has the potential to induce immunity in an immunosuppressed subset of patients (overweight, diabetes, kidney disease and more) that, right now, don’t respond to the current SOCs.
VBI just announced the outcome of a pre-IND meeting with the FDA, and the agency seems happy to allow one global Phase III trial to cover registration applications not just domestically, but also in Canada and Europe. The authorities in these two aforementioned regions also suggested similar earlier this year, and VBI is set to submit trial applications to each in the coming months.
Once these applications are green-lit, the company will kick off the global Phase III study, with likely initiation in late 2017 or early 2018.
As of this writing, Samuel Rae did not hold a position in any of the aforementioned securities.