There's been some great news lately for people with food allergies, high cholesterol, and autoimmune disorders. Fresh from its initial public offering, Aimmune (NASDAQ:AIMT) provided more evidence that its lead program can tune down increasingly common peanut allergies. RNA interference pioneer Alnylam (NASDAQ:ALNY) might have a challenger in the next-generation cholesterol-fighting space. And after scuttling one of its mid-stage lupus candidates earlier this year, it looks as if AstraZeneca (NYSE:AZN) has a chance with anifrolumab in a larger phase 3 trial.
Working for peanuts
Now that many schools are banning foods containing peanut anything, Aimmune's lead product, AR101, is getting a lot of attention. According to the company, the drug is a combination of "peanut flour and pharmaceutical-grade ingredients" designed to desensitize patients to peanut proteins.
Just ahead of its $160 million IPO this August, the company released results from a 49-patient double-blind study that no doubt fueled the offering's success. All 23 patients receiving AR101 were able to tolerate exposure to 443 mg of peanut protein after about 20 weeks on therapy. That's not enough to enjoy even an airline-sized bag of peanuts, but it should be enough to avoid a trip to the emergency room when someone accidentally eats something he or she shouldn't.
In the follow-on study, patients rolled over from the placebo group to AR101 showed results consistent with the previous study. The second time around, investigators also tried a "maximum challenge" exposure test after an additional 12 weeks of maintenance dosing with AR101. Aimmune didn't break out numbers, but "many patients" tolerated a cumulative 2,043 mg of peanut protein.
Before you start stocking up on peanuts again, there were only 49 patients in the initial phase 2 trial. Before placing a bet on such a small and volatile stock, you might want to look for more evidence AR101 can be taken long term without any serious side effects.
The company plans to begin a 500-patient pivotal trial beginning next year. It had better step on it, because DBV Technologies is nearing the finish line with its own peanut allergy desensitizer. The FDA has tagged both of them as "breakthrough therapies,"and the race to be first on the market will be a close one. A 2010 study more than 2% of Americans under 18 reported some form of nut allergy. A drug reaching just a fraction of the available patient population would lead to huge gains for Aimmune, but beware. Without another candidate in clinical trials, any setbacks with AR101 would be disastrous.
Another PCSK9... sort of
With their own next-generation cholesterol lowering therapies just picking up steam, Amgen, Sanofi, and Regeneron would probably like to pretend Alnylam's candidate never existed.
Repatha and Praluent lower "bad" cholesterol by inhibiting the PCSK9 protein. This is especially helpful for a large cross-section of people who are intolerant or unresponsive to statins. Estimates of the available market vary, but it is large enough that analysts expect both drugs to become multi-billion dollar blockbusters. While that would be a nice bump for the likes of Amgen and Sanofi, a win here would lead to huge gains for not-yet-profitable Alnylam.
Developed in partnership with The Medicines Company, ALN-PCSsc also takes advantage of the PCSK9 pathway, but with a twist. Instead of inhibiting PCSK9, this drug prevents cells from producing it in the first place.
Previously disclosed results of a phase 1 study showed Alnylam's drug can lower LDL-cholesterol at a rate similar to existing PCSK9 drugs. The new data confirms that the response is incredibly durable. This result suggests that it can do the job with twice-annual dosing, through subcutaneous injection. That's far more convenient than Repatha and Praluent, which for most patients requires a shot every other week or once a month.
The data so far may be compelling, but it's still very early in the drug's development. The phase 1 trial enrolled just 69 patients who were randomized into 13 groups receiving either placebo or various dosage levels. It's hard to draw meaningful conclusions from such small groups. That's why investors will want to keep their eyes open for results from a 480-patient phase 2 study set to begin before the end of the year.
Finally, a winner in lupus?
AstraZeneca, through its biotechnology subsidiary MedImmune, presented the best news sufferers of lupus have heard in a long time. According to Bing Yao, a senior VP at MedImmune, patients with lupus have seen only one new treatment during the past 60 years. Yao didn't specify, but he's probably referring to GlaxoSmithKline's Benlysta. Even though it's been on the market for a few years, sales of the drug continue to disappoint.
While most patients with milder forms of the disease go undetected, about 358,000 patients in the U.S. are diagnosed and under treatment. Those treatment options have improved greatly over the past several decades, but a 15-year survival rate of about 80% means there's plenty of room for improvement. Analysts estimate an effective treatment for Lupus could reach over $3 billion per year in sales. After years of sagging revenues, that could boost AstraZeneca's top line by more than 10%.
Recent results from AstraZeneca suggest that anifrolumab could provide that improvement. Nearly twice as many patients responded to a 300mg dose of first-in-class 1-interferon inhibitor than placebo after 169 days of treatment. Recently released results show the number of responders after 365 days confirms the trend.
The total number of serious adverse events were lower in the anifrolumab group compared with those on placebo. One reason could be that patients taking anifrolumab were able to reduce their dependence on steroids.
Before you go popping champagne corks, there are some causes for concern. For starters, fewer patients responded to the higher 1,000 mg dosage. Generally, regulators like to see dose-dependent responses, meaning the higher the dose the stronger the response. However, 300 mg will be the maximum dose in a future trial.
More importantly, the thing to look out for with this or any drug that suppresses immune function is an increase in opportunistic infections. That's the sort of thing that could bring the whole program to a halt. There was an increased rate of herpes zoster and influenza infection in patients taking anifrolumab.
An 810-patient phase 3 trial is under way, with data expected some time in 2018 that could support a regulatory submission in 2019. Let's hope this antibody can maintain its safety profile for AstraZeneca and the lupus community.