Merck: Good news, bad news

FDA nixes new combination cholesterol drug (at least for now) but Merck gets positive Phase III results from trial of allergy immunotherapy tablet for ragweed pollen

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WHITEHOUSE STATION, N.J.—Monday was a mixed bag for Merck, known as MSD outside the United States and Canada. On the one hand, a Phase III clinical trial for an allergy immunotherapy tablet (AIT) for ragweed pollen yielded good results; on the other hand, the U.S. Food and Drug Administration (FDA) has decided against approving Merck's new combination cholesterol drug for now.
That latter bit of news, though perhaps more significant to Merck, is also the shortest, so we'll start with the bad news. In an FDA Complete Response Letter regarding Merck's New Drug Application (NDA) forezetimibe and atorvastatin tablets, an investigational combinationmedicine, the verdict is that FDA isn't quite ready to give the go-ahead for what is essentially a mash-up of Merck's own cholesterol drug Zetia with a generic version of rival Pfizer Inc.'s Lipitor, which had been the best-selling cholesterol drug of all time.
In the letter, the FDA advised Merck that it has completedits review of the NDA submission and stated that additional data areneeded. Merck says it plans "to discuss next steps with the agency in the nearfuture, including new data that are expected to be available later thisyear, which may address the FDA's comments."
On the good news side, results from aPhase III clinical study of Merck's investigational AIT for ragweed pollen showed that the useof ragweed AIT significantly reduced the total combined score thatmeasured nasal and eye symptoms and use of rescue allergy medicines,compared to placebo, in ragweed-allergic adults with or without asthma.The study was conducted during peak ragweed pollen season. These datawere presented recently at the American Academy of Allergy, Asthma &Immunology (AAAAI) Annual Meeting in Orlando.
Merck's AIT is an investigational, dissolvable oral tablet designed totreat the underlying cause of allergies, and is being studied todetermine whether AIT may help to prevent allergy symptoms by generatingan immune response to protect against targeted allergens. The companyis investigating disease-modifying AITs for the treatment of allergiescaused by ragweed pollen, grass pollen and house dust mites. Merck haspartnered with ALK-Abello to develop AITs to treat these allergens inNorth America and plans to file NDA) for itsragweed and grass AITs with the FDAin 2013.
"Merck is pleased that patients who took its AIT in this studyexperienced a significant reduction in the nasal and eye symptoms causedby ragweed allergies, and these positive results are an important stepin the development of this investigational therapy," said Dr. Rupert Vessey,senior vice president and franchise head, Respiratory &Immunology, Merck Research Laboratories. "We are committed to providingphysicians and patients with a broad range of treatment options forallergies and other respiratory diseases."
The multicenter, double-blind, randomized, placebo-controlled,parallel group Phase III trial was designed to assess the efficacy andsafety of two doses of ragweed AIT. The study involved 565 adults whowere 18 to 50 years old with ragweed-induced allergicrhinoconjunctivitis, with or without asthma. The majority of thesepatients (85 percent) were sensitive to multiple allergens. Patientswere randomized to receive a once-daily tablet of Ambrosiaartemisiifolia (ragweed) allergen extract at a dose of 6 Amb a 1-U or 12Amb a 1-U or placebo for approximately 16 weeks prior to and throughoutthe ragweed pollen season, for a total treatment period of 52 weeks.
During ragweed pollen season, patients recorded their symptoms andrescue medication use daily in electronic diaries. The primary efficacyassessment was total combined score, which was the sum of the dailysymptom score and the daily medication score averaged over the peakragweed pollen season (peak season was defined as the 15 consecutivedays with the highest 15-day moving average pollen count). The dailysymptom score consisted of daily ratings of four nasal symptoms (runnynose, blocked nose, sneezing, and itchy nose) and two eye symptoms(gritty eyes and watery eyes) on a scale from zero (no symptoms) tothree (severe symptoms), and the daily medication score assigned a scorebased upon the type and amount of rescue medication used each day. Thesafety profile of the study drug was monitored via adverse event reporting, as well as by an external data and safety monitoringcommittee.
During peak ragweed season, patients treated with ragweed AIT 12 Amb a1-U or AIT 6 Amb a 1-U showed 27 percent and 21 percent reductions intotal combined score, respectively, relative to placebo (p=.0002 andp=.0039). Specifically, both doses of ragweed AIT resulted insignificant reductions in daily symptom score relative to placebo duringpeak ragweed season (17 percent for AIT 12 Amb a 1-U, p=.0144; and 14percent for AIT 6 Amb a 1-U, p=.0472). Ragweed AIT 12 Amb a 1-U and AIT 6Amb a 1-U also yielded 45 percent and 34 percent reductions in dailymedication score, respectively, relative to placebo (p=.0001 andp=.0039) during peak ragweed pollen season, a time when rescuemedications are expected to be utilized most.
The most frequently reported treatment-related adverse events were itchiness of themouth and ear and throat irritation. Two patients received epinephrineduring the course of the study. There were no reports of death, systemicallergic reactions or life-threatening events over 52 weeks. 

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