President Obama is continuing to push for lower health-care costs, despite what many consider to be more pressing near-term issues.

And that should scare the cr- ... well, should really scare drugmakers and their investors.

I'm not so concerned about companies being forced to lower the cost of their current drugs as I am worried about whether new drugs will be able to gain traction. Health insurers are continuing to shift patients to low-cost generics. For instance, my copayment is twice as much for branded drugs as for generics and Target's (NYSE:TGT) and Wal-Mart Stores' (NYSE:WMT) $4 generic drug deals also encourage a move away from branded drugs. With more drugs going off-patent in the not-too-distant future, the competition from generic drugs is only going to get worse.

Keeping those high margins
In an era where the government wants to do comparative studies to see which drugs work the best, me-too drugs just aren't going to cut it. Changing a molecule slightly -- like Wyeth and Johnson & Johnson (NYSE:JNJ) have done with Pristiq and Invega, respectively -- without showing that the drugs have a clear advantage is a recipe for poor sales. The original drugs will go off-patent and doctors won't have a clear reason to prescribe the successor.

The solution is for companies to run head-to-head trials with drugs that are currently on the market. Both Amylin Pharmaceuticals and Novo Nordisk have used this strategy for their diabetes drugs. Running head-to-head trials is a risky strategy -- marginal benefits might not justify the higher costs -- but companies don't have much other choice if they're in a field full of competitors.

Two potentially game-changing drugs
Another equally risky option is to try and treat a disease for which no good treatment exists. It's just as risky as head-to-head trials because there's usually a reason that no one has been able to come up with a good treatment option. But the potential payoff is tremendous.

For instance, the current treatment options for hepatitis C patients, pegylated interferons, are pretty pathetic. Both Roche's Pegasys and Schering-Plough's (NYSE:SGP) PegIntron have a cure rate under 50% for the first round for genotype 1, which drops considerably on a second attempt. That leaves quite a bit of room for improvement.

The farthest along in the clinic is Vertex Pharmaceuticals' (NASDAQ:VRTX) telaprevir. In a phase 2 trial of uncured patients, the drug was able to cure 51% of the patients compared to just 14% that were cured with a second round of pegylated interferon.

Telaprevir is currently in phase 3 trials in untreated patients, and if it can put up numbers like it did with treatment-experienced patients, it should have no problems getting past the FDA. The bigger risk is that drugs farther behind it in the clinic -- Schering has one that's extremely close -- will unseat it before Vertex is able to fully capitalize on telaprevir.

A little more risky in the efficacy arena, but also with huge potential benefit, is Elan (NYSE:ELN) and Wyeth's Alzheimer's drug, bapineuzumab. The drug had mixed phase 2 results and looks like it may only be working in a subset of patients. But with the fairly unimpressive drugs from companies like Forest Labs and Pfizer (NYSE:PFE) as patients' best treatment options, even if bapineuzumab should have no problem becoming a blockbuster (even if it only works in a subset of patients). It'll be a while before investors get the phase 3 results, but those could be worth waiting for.

Investing in drug companies in this time of "change" doesn't have to be scary. You've just got to find rule breaker-type drugmakers, because playing by the rules isn't going to cut it anymore.

It should come as no surprise that Vertex and Elan are Motley Fool Rule Breakers picks. The newsletter is always on the hunt for hot drug stocks and other cutting-edge picks. Click here to see all of our latest discoveries with a free 30-day trial subscription.

Fool contributor Brian Orelli, Ph.D., doesn't own shares of any company mentioned in this article. Novo Nordisk is a Motley Fool Global Gains recommendation. Johnson & Johnson is an Income Investor pick. Pfizer and Wal-Mart Stores are Inside Value recommendations. The Fool has a disclosure policy.