If the FDA approves the new obesity drugs, will REMS crash the party?

Wow!  A lot has happened since my last blog post.  Two of the three new obesity drugs up for approval (Qnexa from Vivus and Lorquess from Arena) both received positive responses from their respective FDA advisory panels despite all of the pessimism from outside observers.  Of course, both drugs have yet to be officially approved by the FDA and they could still be rejected, just ask Intermune.

However, I refuse to be one of the pessimists and I do believe that at least the one of the two drugs will get the FDA’s stamp of approval, if not both.  However, before everyone breaks out the champagne and starts celebrating, we need to talk about something called REMS.

REMS stands for Risk Evaluation and Mitigation Strategy and was brought into effect through the 2007 Food and Drug Administration Amendments Act.  It was introduced to allow the approval of drugs that have a both an obvious benefit, but also substantial risks.  Think of it as a finger that tips the risk-benefit scale more to the benefit side.  REMS provides an additional level of control over drugs that otherwise couldn’t be approved for unrestricted use in the general population. If you’re interested in a more detailed overview of REMS, there are some great summaries here and here.

I’m sure you’re wondering what these controls look like. Well, they come in a number of different flavors.  Here is a list of typical REMS requirements, starting from the least onerous:

1. Medication guide
2. Communication plan
3. ETASU (Elements to assure safe use)
4. Implementation system

The most basic REMS is a medication guide.  The guide provides additional information for the prescriber so that they are completely informed of the risks and benefits of the drug and can fully inform the patient taking the drug.  It lays out the concerns around adverse events and procedures the prescriber can follow to minimize those risks.  The manufacturer provides a draft guide to the FDA, who, if satisfied it contains all the necessary information, approves it.

Pretty simple so far, right?  Medication guides are the most common type of REMS and account for around 2/3 of all the drugs that have REMS requirements.  The other 1/3 aren’t so lucky, some of those have ETASU requirements.

The types of controls within an ETASU can also vary.  They can be as simple as providing formal training for the prescriber so that he or she understands how the drug should be administered, how to educate the patient and how to recognize and report any adverse events.  However, on the other end of the spectrum, ETASU controls can also limit who can prescribe the drug, which pharmacies can fill the prescriptions and where the drug can be administered.  Where the problem comes in is that you can’t just have these controls, you need mechanisms in place to make sure they are being followed.  This requires pharmacists, nurses, physicians and hospitals to take on an incredible administrative burden and a burden that they don’t get reimbursed for.  That is how REMS can really put the squeeze on a new drug.  If you are a physician who has the choice of prescribing a drug where all you do is write a script versus a drug where your staff has to spend an hour filling out forms just so that the patient can drive across town to the one pharmacy that stocks it, which one would you prescribe?  Even if a drug with an onerous REMS is the only drug available to treat a condition, how often  will physicians think “I would love to use this drug, but I can justify the burden on me and my staff?”

Both Qnexa and Lorquess have the potential to be approved with a REMS requirement.  Qnexa contains topiramate, which is known to increase the risk of cleft palate in mothers who take the drug while pregnant.  REMS seems like a great way to keep Qnexa out of the hands of pregnant women, similar to Revlimid (which has an incredibly onerous REMS).  Lorquess has the FDA concerned about a possible increased risk of cardiovascular events and REMS would be a great way to collect patient data (through a registry) to determine if that risk is meaningful.

If either of these drugs ends up with strict REMS requirements, you can expect all those financial analysts to quickly revise their revenue estimates and the price of the companies’ stock to react accordingly.  So save your champagne until the FDA decisions come out on June 27th (Lorquess) and July 20th (Qnexa).  You may just end up saving it for New Year’s Eve.