Tavapadon Update

Publication of a Phase 3 trial of the dopamine agonist tavapadon in mild PD shows that a new option will be available soon for people with PD.

Tavapadon is a unique dopamine agonist, stimulating different dopamine receptors than the currently available agents.

What I think of as first generation dopamine agonists – the ones that are available now (ropinirole, pramipexole and rotigotine) act via D2/D3 receptors to reduce the brake on movement. In contrast, what I call second generation drug acts via D1/D5 receptors to stimulate movement.

The trials that I expect to yield FDA approval for tavapadon studied the effects of the drug compared to placebo. They showed benefit in people with mild PD [TEMPO-2] as well as those with more advanced disease as defined by motor complications [TEMPO-3]. It is a strong database. But we don’t have data to tell us how to use 1^st-gen vs. this 2^nd gen dopamine agonist.

Open questions include:

· Does one more potent improve movement than the other?

· Is one approach better tolerated with less side effects?

· Are there situations where a person should switch from 1^st-gen to this 2^nd-gen therapy?

· Could the two together or rotating between the two be the optimal approach?

With such unanswered questions, how are we to know how to use this new therapy? Conducting proper randomized clinical trials focused on each question is the only way.

Trials Comparing Similar Drugs: Feasible and Important

Abbvie is developing tavapadon after it was initially discovered by scientists at Pfizer. As a commercial entity, why would Abbvie conduct comparative studies that risk their drug being shown to be no better than a 1st-gen dopamine agonist, especially considering how cheap they are compared to a newly launched brand-name drug? Consider a couple of lessons.

1. Several companies selling the cholesterol-lowering statins were battling for market share (behind Lipitor). Bristol-Myers Squibb (BMS) sought to increase its share and launched a large-scale, multi-center, blinded, randomized clinical trial comparing its drug (Pravachol) to Lipitor. No one expected the two drugs to have equal cholesterol lowering effects, as Lipitor more potently lowered cholesterol. Instead, the trial focused on whether the clinical impact of any cholesterol lowering were similar or different. When I spoke with cardiologists about the trial, they seemed convinced that BMS knew something that made them confident enough to spend the millions of dollars the trial would cost – and so continued to write prescriptions for Pravachol. In the end, Pravachol was shown to be inferior (though still better than placebo). BMS did the right thing, though their gamble failed.

2. When the second beta-blocker was approved for treatment of heart failure, GlaxoSmithKline (GSK) was concerned that its drug (Coreg) could lose market share – including to a generic beta-blocker. It launched a major clinical trial comparing its brand name drug to the generic. Again, doctors talking about the trial seemed convinced that GSK knew something that made it risk its beta-blocker franchise. In the end, Coreg was proven to be clinical superior to the generic beta-blocker metoprolol (that was also effective). GSK’s did the right thing and their gamble paid off.

Abbvie could to the right thing, but If such a trial is not already being planned, I am not optimistic Abbvie is likely to conduct such a trial.

A Call to Action

If Abbvie has not already factored in this gamble to their soon to be launched drug, I am not optimistic they are likely to announce such a trial.

But there is a way. The NIH, the Michael J. Fox Foundation, the Parkinson’s Foundation and Cure Parkinson’s – amongst others – could band together and make it happen. This is not merely a scientific curiosity. This is a major clinical need. And if you agree, tell these Foundations that you want to know the answers to these questions.