By Cort Johnson
Tomnya had everything going for it; a novel approach to pain and good Phase II trial results, but Tonix’s reformulation of Flexeril that was expected to help with both sleep and pain tanked in its critical Phase III trial. Cort Johnson explains what happened with it and gives us an update on four other drugs that may get approved for FM in the next couple of years.
Five Drug Possibilities
A recent report listed four drugs that are expected to be approved for fibromyalgia in the next five or so years. Adding Dr. Pridgen’s antiviral / anti-inflammatory drug combo to that list gives us five new drug possibilities for FM.
Now there are four.
Promising Drug Fails
Tonix Pharmaceuticals recently announced that one of the most promising drugs –TNX-102 – failed to meet its primary endpoint during a Phase III trial. With that, its stock price plunged by 70% wiping out $30 million dollars in value.
It wasn’t supposed to go like this. TNX-102, an updated form of Flexeril, had been researched extensively. Eleven studies including four in fibromyalgia suggested that Tonix was really onto something. In fact, Tonix was so eager to get the drug to the market that it reportedly started the critical Phase 3 before the Phase 2 trial had even ended.
It had reason to be optimistic. Tonix had reformulated Flexeril to remove a compound that was limiting the popular drug to short-term use. It repackaged the new drug in a format (sublingual) that shot the drug straight into the body, allowing a significant reduction in the dose. Phase II studies indicated the drug was safe and able to improve both sleep quality and reduce pain at the same time.
With many FM patients not receiving significant benefits from “the big three” drugs (Lyrica, Cymbalta, and Savella), Tonix, a small pharmaceutical company, must have thought the sky was the limit.
The Phase III trial, however, failed and it failed in the worst way possible; it failed to meet its primary endpoint – reducing pain significantly in at least 30% of the people taking it. Drugs can fail to meet their secondary endpoints without too much damage, but drugs that miss their primary target are in real trouble.
Tonix’s CEO stated that the 500-person study indicated that “TNX-102 SL showed broad beneficial effects across key fibromyalgia symptoms” as he announced Tonix was discontinuing its FM trials and turning to PTSD.
Watching TNX-102 bite the dust was more than a bit dismaying but is not entirely surprising. It’s certainly not the first highly touted drug to get knocked out in a Phase 3 trial.
Phase III Study Missteps Not Uncommon
CMX-001 or Brindcifovir was a hot, hot, hot upgrade of the antiviral anti-herpes virus drug Vistide. It, too, had been repackaged to enhance effectiveness and dramatically reduce side effects. A significant amount of research suggested the newly formatted herpes virus drug was effective against many types of viruses leading the FDA to give it fast-track status for no less than three separate viruses.
It, too, sailed through large Phase 2 trials and then stunk it up in the big Phase 3 trial (perhaps because of something the doctors unwittingly did). Subsequently, Chimerix, its manufacturer, halted two more Phase 3 trials. The company is sticking with one Phase 3 trial but is going back to the drawing board and re-embarking on more Phase 2 trials. Brincidofovir was considered by many to be a drug that could not fail.
Likewise, in ME/CFS the phase II Synergy trial combining methylphenidate and mitochondrial nutrients seemed to be a lock before it, too, failed to meet its primary endpoint. The unusually high placebo effects suggested there may be quite a few ways to fail a clinical trial.
Brincidofovir and Chimerix are still around, but the same might not be true for TNX-102 and Tonix. Tonix hoped to move forward with PTSD trials, but the company’s huge stock price plummet and the need to raise a large amount of money for PTSD trials make that possibility unlikely.
It would be a shame to lose this drug entirely. A successful PTSD trial would make TNX-102 – which surely must help some FM patients – available off-label.
It’s a tough world out there in the drug approval business.
One Down – Four to Go.
Meanwhile, we have at least four more drug possibilities exist.
Mirogabalin
Tonix apparently went all in on its 500-person TNX-102 trial, but the Mirogabalin trial is something else. Produced by the huge Japanese pharmaceutical company, Daiichi Sankyo, the FM mirogabalin trial numbers no less than 1,000 participants.
Mirogabalin, a calcium channel blocker, is the latest attempt by a pharmaceutical company to capitalize on the Neurontin / Lyrica line of drugs. Mirogabalin’s big potential plus is its ability to stop the transmission of pain signals without producing the side effects seen in Lyrica. It’s able to do this by selectively binding to a particular section of the calcium channels that transmit pain.
Considerably lower dropout rates in the 450-person phase II trial mirogabalin (18%) than for Lyrica (27%) suggest Daiichi Sankyo may be onto something. Completion of the drug trial, which is filled up, is expected in March 2017.
Time-Release Form of Lyrica and TD-9855
Two other possibilities are a time-release formulation of Lyrica and TD-9855, a norepinephrine serotonin and reuptake inhibitor. The time-release form of Lyrica would add some convenience but not much more, and the history of NSRIs in FM is not particularly encouraging. Plus, no T-9855 Phase 3 trials are under way.
Pridgen’s Antiviral Approach to Fibromyalgia
Dr. Pridgen’s novel approach to fibromyalgia involving an antiviral drug (Famvir) and an anti-inflammatory drug with antiviral properties (Celebrex) could upend decades of thinking on FM. The Phase 2 trial was moderately successful, but Pridgen believes the next trial using better dosing will get better results. Pridgen’s currently raising funds for a Phase 3 trial. Expect a more detailed update on Pridgen’s progress soon.
Other Possibilities
These drugs present just some of the possibilities that may become available in the next four or five years. People with FM can benefit from drugs not approved for FM and other pain drugs are being assessed. Plus, non-drug trials including several brain stimulation trials, a trial using the Bemer device, a passive heating trial and others are underway in FM.