FDA: Recall of Montelukast tablets by Camber due to wrong drug in bottles

The U.S. Food and Drug Administration is warning consumers and health care professionals about a voluntary recall of one lot of Montelukast Sodium Tablets – lot number MON17384, expiration 12/31/2019 – by Camber Pharmaceuticals, Inc., Piscataway, N.J. Sealed bottles labeled as montelukast sodium tablets, 10 milligram, 30-count bottle from Camber were found to instead contain 90 tablets of Losartan Potassium Tablets, 50 mg.

This tablet mix-up may pose a safety risk as taking losartan tablets when not prescribed has the potential to cause renal dysfunction, elevated potassium levels and low blood pressure. This risk is especially high for pregnant women taking the allergy and asthma medication montelukast because losartan, which is indicated to treat high blood pressure, could harm or kill the fetus. The FDA recommends that consumers who have this recalled product should contact their health care provider or pharmacist immediately.

This recall is not related to the recent valsartan recalls that were due to an impurity, N-nitrosodimethylamine (NDMA).

“We want to ensure that patients who take montelukast are aware of this recall due to the serious risks associated with taking losartan in its place,” said Donald D. Ashley J.D., director of the office of compliance in the FDA’s center for drug evaluation and research. “Patients who take prescription drugs expect and deserve to have the medication their doctor prescribed.”

Montelukast is used to prevent wheezing, difficulty breathing, chest tightness and coughing caused by asthma. It is also used to prevent bronchospasm (breathing difficulties) during exercise and to treat the symptoms of seasonal and perennial allergic rhinitis. Montelukast is in a class of medications called leukotriene receptor antagonists (LTRAs) which work by blocking the action of substances in the body that cause the symptoms of asthma and allergic rhinitis.

Losartan is often used alone or in combination with other medications to treat high blood pressure. Losartan is also used to decrease the risk of stroke in people who have high blood pressure and a heart condition called left ventricular hypertrophy (enlargement of the walls of the left side of the heart).

Patients should contact their health care provider or pharmacist to determine if their medicine has been recalled. Patients should also look at the drug name and company name on the label of their prescription bottle. If the information is not on the bottle, patients should contact the pharmacy that dispensed the medicine.

Montelukast sodium tablets are beige, rounded square-shaped, film coated tablets that are imprinted with “I” on one side and “114” on the reverse. Losartan tablets are white and oval-shaped with the letter “I” imprinted on one side and the number “5” imprinted on the reverse.

Recalled lots of montelukast sodium tablets, USP 10mg have the following information:

• Label: Montelukast Sodium Tablets 10 mg 30 ct
• Lot number: MON17384
• Expiration date: 12/31/2019
• NDC: 31722-726-30

To date, Camber has not received adverse event reports associated with this recall. The FDA encourages health care professionals and consumers to report adverse events to the FDA’s MedWatch Adverse Event Reporting program:

• Complete and submit the report online at www.fda.gov/medwatch/report.htm; or
• Download and complete the form, then submit it via fax at 1-800-FDA-0178.

For more information:

• FDA Recalls

https://www.biospace.com/article/releases/fda-announces-voluntary-recall-of-montelukast-tablets-by-camber-pharmaceuticals-due-to-incorrect-drug-in-bottles/

Aquestive Therapeutics (AQST) Announces Tentative FDA Approval

Aquestive Therapeutics, Inc. (NASDAQ: AQST) today announced that Sympazan™ (clobazam) oral film has received tentative approval by the U.S. Food and Drug Administration (FDA), for the adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome (LGS) in patients 2 years of age or older. Currently, clobazam is marketed as ONFI® and offered in two formulations – either tablet or oral suspension.

“We saw a need in the LGS community for a simpler, more consistent way to administer a full dose of clobazam – and we are now one step closer to bringing this important treatment to patients, caregivers and physicians,” said Keith J. Kendall, Chief Executive Officer of Aquestive Therapeutics. “This tentative approval for Sympazan is a key milestone for Aquestive, as it represents the first in a series of late stage proprietary products Aquestive plans to commercialize once they are approved. We believe Sympazan and our other products in development solve important therapeutic problems, and will meaningfully improve the lives of patients and their caregivers.”

Lennox-Gastaut Syndrome is a severe form of epilepsy that begins in early childhood and is characterized by multiple types of seizures and intellectual disability. LGS patients often have difficulty swallowing pills and large volume suspensions due to physical limitations, behavioral or compliance issues. Challenges with treatment administration can lead to uncertain and inconsistent dosing, and increase the burden of care, particularly for patients that may be combative or resistant to treatment.

Sympazan is a proprietary formulation based on Aquestive’s proven PharmFilm® technology. Multiple pharmacokinetic studies were conducted to compare Sympazan with ONFI. Based on the studies, Sympazan oral film was demonstrated to be bioequivalent to clobazam tablets and have comparable safety.

Final FDA approval for Sympazan is pending the expiration of the orphan drug exclusivity period for ONFI, which is expected in October 2018.

https://www.streetinsider.com/Corporate+News/Aquestive+Therapeutics+%28AQST

FDA nixes Sunovion ADHD treatment

Sunovion Pharmaceuticals Inc. (Sunovion) today announced that the U.S. Food and Drug Administration (FDA) issued a Complete Response Letter for the New Drug Application (NDA) for dasotraline, a novel dual-acting dopamine and norepinephrine reuptake inhibitor (DNRI), for the treatment of attention-deficit hyperactivity disorder (ADHD).

Upon completion of their review, the FDA determined that they cannot approve the dasotraline NDA for the treatment of ADHD in its current form. The Agency indicated that additional clinical data are needed to further evaluate the efficacy and tolerability of dasotraline for the treatment of ADHD. Sunovion plans to meet with the FDA to discuss their comments and determine next steps.

Dasotraline was evaluated in approximately 2,500 children and adults with ADHD in multiple placebo-controlled safety and efficacy studies,^1,2,3,4 as well as two long-term safety studies.

“While we are disappointed with the FDA’s decision, we remain confident in the future of dasotraline,” said Antony Loebel, M.D., Executive Vice President and Chief Medical Officer at Sunovion, Head of Global Clinical Development for Sumitomo Dainippon Pharma Group. “We plan to discuss next steps for the dasotraline ADHD program with the FDA as soon as possible.”

Dasotraline is also being studied for the treatment of moderate to severe binge eating disorder (BED) in adults in the U.S. Data from two positive pivotal studies^5,6 will support an expected marketing application submission to the FDA for dasotraline to treat BED in FY2018.

https://www.biospace.com/article/releases/fda-issues-a-complete-response-letter-for-new-drug-application-for-dasotraline-for-the-treatment-of-adhd/

After Astra’s failure, lupus attention turns to Aurinia

Today’s phase III flop of Astrazeneca’s anifrolumab makes Aurinia’s voclosporin the next lupus asset with a near-term pivotal readout. Aurora, Aurinia’s phase III trial in lupus nephritis, is to complete enrolment in the next quarter, and could yield data towards the end of 2019. Anifrolumab flunked the first of two pivotal systemic lupus erythematosus studies, Tulip-1, failing to show an effect on four-point SLE responder index improvement at 12 months versus placebo. As such, chances of success in Tulip-2, which has a similar design but tests only 300mg rather than three anifrolumab doses, are slim. Another lupus player to watch is the French micro-cap group Neovacs, which claimed a phase II win last month. However, close inspection of the data on Neovacs’ IFNα-Kinoid revealed a primary endpoint miss, and a hit in reducing an interferon signature. Aniforolumab was also being developed with an interferon gene signature test, and Neovacs’ hopes hinge on attracting a partner to fund phase III. For investors who have faith in Neovacs there is a further cautionary tale from Astra: anifrolumab at 300mg succeeded in phase II, but the effect vanished in the more rigorous pivotal setting.

SELECTED CLINICAL PROJECTS FOR TREATING LUPUS
Project	Company	Mechanism	Trial ID
Phase III
Voclosporin	Aurinia Pharmaceuticals	Calcineurin inhibitor	NCT03597464
Olumiant	Lilly	Jak1 & 2 inhibitor	NCT03616912
Stelara	Bristol-Myers Squibb	IL-12 antibody; IL-23 receptor antibody	NCT03517722
Phase II
XmAb5871	Xencor	CD19 antibody	NCT02725515
CC-220 (iberdomide)	Celgene	Immunomodulator	NCT03161483
Filgotinib + GS-9876	Galapagos/Gilead	Jak1 inhibitor + Syk inhibitor	NCT03134222
BI 655064	Boehringer Ingelheim/Abbvie	TNFRSF5 antibody	NCT02770170
Evobrutinib	Merck KGaA	BTK inhibitor	NCT02975336
Gazyva	Roche	CD20 antibody	NCT02550652
Fenebrutinib	Roche	BTK inhibitor	NCT02908100
RSLV-132	Takeda/Resolve Therapeutics	IFN alpha inhibitor	NCT02660944
Dapirolizumab	Biogen/UCB	TNF ligand superfamily 5 antibody	NCT02804763
BIIB059	Biogen	BDAC2 antibody	NCT02847598
IFNα-Kinoid	Neovacs	Anti-interferon alpha vaccine	NCT02665364
ILT-101	Iltoo Pharma	IL-2 regulator	NCT02955615
Lenabasum	Corbus Pharmaceuticals	CB2 agonist	NCT03093402
CFZ533	Novartis	TNFRSF5 antibody	NCT03610516
Source: EvaluatePharma.

http://www.evaluate.com/vantage/articles/news/snippets/after-astras-failure-lupus-attention-turns-aurinia

Fosun ‘massively’ fakes API production data, bribes regulators: whistleblower

After Zhejiang Huahai Pharmaceutical’s tainted valsartan API and Changchun Changsheng Life Sciences’ fabricated vaccine production data exposé, China’s drug industry could be dealing with another major manufacturing scandal. This time, the protagonist is Fosun Pharma.

In an open letter (Chinese) to the drug regulator in Chongqing, China, self-claimed employees of Chongqing Pharma Research Institute, a unit of Fosun Pharma, depicted a “chaotic” production scene at the company. It alleged that the firm illegally changed production processes of almost all its APIs, while management pushed employees to fabricate data and manipulate testing readouts to achieve passing results.

The anonymous whistleblowers claimed that the company—which previously has been cited by U.S. regulators—conjured up fake sets of records to earn GMP certificates for a new production site, and that it bribed local drug officials to get go-aheads for proposed production changes to antipsychotic drug aripiprazole and chemotherapy pemetrexed disodium.

Refuting the whistleblower accusation, Fosun said in disclosures (PDF) published Friday that it made all existing products using approved production processes, and that any adjustments have been approved by or filed with authorities.

“The group places great emphasis on the quality and risk management throughout the life cycle of its products,” said Fosun. “The group has adopted and implemented quality and safety control mechanisms and adverse drug reaction monitoring mechanisms at each stage of the production chain.”

Chongqing FDA responded to the letter Friday, saying it has dispatched an inspection team. Fosun also said the agency made an unannounced inspection a day before posting the open letter on its website but hasn’t made any conclusive opinion.

Because the whistleblowers didn’t provide real personal information, Chongqing’s drug regulator is calling for more detailed evidence to support their claims.

However, the Fosun unit is no stranger to such accusations. In a warning letter last February, the U.S. FDA identified “significant deviations” from cGMP standards at the firm, with data integrity notably mentioned as a problem, where the agency made a long list of recommendations for remediation.

Fosun itself revealed that the company’s new site in Chongqing was slapped with a Form 483 after an FDA pre-approval inspection last November. According to Fosun, the problem is related to API aripiprazole, “for its deficiency of invalidated OOS result in the testing (deviation investigation).” In addition, it said it “has dealt with and restructured the key leaders and the relevant responsible personnel … in a serious manner” as a result of the warning letter, and it’s taking steps to rectify the problems cited.

Last year, Chongqing Pharma Research Institute generated revenue of 77.8 million Chinese yuan ($11.4 million), of which 26% came from business abroad, said Fosun.

The snafu comes less than two months after valsartan API supplied by Zhejiang Huahai sparked a worldwide recall after the company reported a possible carcinogen called N-nitrosodimethylamine (NDMA) in the drug. It also follows a high-profile vaccine scandal in which Changsheng was found to have provided ineffective vaccines to children and systematically fabricated production data to cover up its violations. The case saw the resignation and dismissals of top government officials—including former China FDA chief Bi Jingquan—as the country’s top leaders worked to restore confidence in China’s drug industry and pacify public anger.

https://www.fiercepharma.com/manufacturing/fosun-pharma-massively-fakes-api-production-data-and-bribes-regulators-whistle-blower

FDA eases trade between US, foreign partners via food export certification

Today the U.S. Food and Drug Administration announced its new export certification program for certain FDA-regulated food products and fees it will assess for issuing new export certifications to U.S.-based manufacturers or exporters of these products. Export certification under the Federal Food, Drug & Cosmetic Act (FD&C Act) provides U.S. exporters another tool to facilitate exports to countries that import food products from the U.S.

“We anticipate that this new export certification will facilitate trade by assisting U.S. food exporters in fulfilling importing country requirements for FDA certification of FDA-regulated food products,” said FDA Commissioner Scott Gottlieb, M.D. “While American food standards are among the most stringent in the world, the FDA recognizes that some U.S. trading partners seek additional assurance that imported food products are produced under applicable requirements, and may request specific language or product information on export certificates. The new export certification program will continue the FDA’s efforts to help facilitate American global exports and boost our nation’s economy.”

In 1996, Congress added a new statutory provision to the FD&C Act that stated any person who exports a drug, animal drug or device may request the FDA certify in writing that the exported product meets certain requirements, and that the FDA shall issue such a certification within 20 days upon a showing that the product meets those requirements. The law also authorized the FDA to charge up to $175 for each such certification. However, this provision did not include FDA-regulated foods. When Congress passed the FDA Food Safety Modernization Act (FSMA) in 2011, it added foods to the list of covered products.

The FDA’s new export certification will implement the FSMA amendment. Prior to the launch of this new certification program, the FDA issued other types of certifications for exported foods.

The FDA’s export certification program for foods is intended to be complementary to export certification for foods currently issued by other U.S. government agencies. As the FDA launches its new export certification program for foods, the arrangements currently in place for certain food commodities with other U.S. government agencies will remain the same. The FDA has and will continue to coordinate and work with other U.S. government agencies on export certification and will partner in interagency consultations for any new requests from foreign governments to ensure the needs of U.S. exporters are met.

The FDA will continue to issue the current “Certificate of Free Sale” for dietary supplements, medical foods and foods for special dietary uses.

The FDA will begin issuing and collecting fees for the new export certificates starting Oct. 1, 2018. For more information, see the Federal Register Notice.

https://www.biospace.com/article/releases/fda-helps-facilitate-trade-between-u-s-and-foreign-trading-partners-with-new-export-certification-program-for-food/

FDA Approves Eight Novel Drugs in August

The U.S. Food and Drug Administration (FDA) has had a busy August. In addition to the number of draft guidances the agency issued during the month, the FDA has also been busy approving a number of new treatments for a variety of diseases.

The FDA gave the go-ahead to eight novel drugs in August. The FDA also approved a number of other drugs during the month that are under different classifications. Novel drugs are classified as new molecular entities. In its classification, the FDA said: “many of these products contain active moieties that have not been approved by FDA previously, either as a single ingredient drug or as part of a combination product.”

The first novel drug to gain approval was for Japan-based Kyowa Kirin. The FDA approved Poteligeo (mogamulizumab-kpkc) injection for intravenous use for the treatment of adult patients with relapsed or refractory mycosis fungoides or Sézary syndrome, two types of non-Hodgkin lymphoma. The treatment is intended for patients who have had at least one prior systemic therapy.

Alnylam’s Onpattro (patisiran) was approved Aug. 10 for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. The FDA gave the greenlight for this revolutionary treatment on Aug. 10. Not only was Onpattro the first novel drug of August, it is the first and only RNA interference (RNAi) therapeutic to ever be approved. The drug was approved with a priority review status. RNAi is designed to prevent the production of problematic proteins that are the basis for many diseases.

Also on Aug. 10, the FDA gave the green light for New Jersey-based Amicus Therapeutics’Galafold (migalastat), the first oral medication for the treatment of adults with Fabry disease. Fabry disease is a rare and serious genetic disease that results from the buildup of a type of fat called globotriaosylceramide (GL-3) in blood vessels, the kidneys, the heart, the nerves and other organs.

The FDA also approved TherapeuticsMD’s Annovera on Aug. 10. Annovera (segesterone acetate/ethinyl estradiol vaginal system) is the first long-acting prescription birth control that is patient-controlled, procedure-free and reversible, according to the company. Annovera is a small, soft flexible ring that prevents ovulation for an entire year (13 cycles) and can be inserted and removed by a woman at her discretion in repeated four-week cycles

On Aug. 20, France-based Biocodex snagged approval for Diacomit (stiripentol) for the treatment of seizures associated with Dravet syndrome in patients two years of age and older who are already taking clobazam. Dravet syndrome is an early onset epileptic syndrome that is thought to affect approximately 2,000 to 8,000 patients in the U.S.

On Aug. 23, Italy-based Dompe secured approval for Oxervate, a treatment for eurotrophic keratitis (NK), a rare and progressive eye disease that can lead to corneal scarring and vision loss. The rare orphan disease affects fewer than 65,000 people in the United States. The disease results from impaired function of corneal nerves. Oxervate, an ophthalmic solution, is based on cenegermin-bkbj, a novel recombinant human nerve growth factor (rhNGF) that is structurally identical to the nerve growth factor (NGF) protein that is made in the human body, including in the ocular tissues, the company said.

Also on Aug. 23, Shire plc snagged approval for Takhzyro (lanadelumab-flyo), a prophylaxis to prevent attacks of hereditary angioedema (HAE) in patients 12 years of age and older. Takhzyro was approved based off multiple late-stage trials that demonstrated efficacy in treating HAE, a rare, genetic disorder estimated to affect about one in 10,000 to one in 50,000 people worldwide. The condition results in recurrent, localized edema (swelling).

The latest novel drug approved by the FDA was late Aug. 30. Merck snagged approval for HIV-1 treatment Pifeltro, a new non-nucleoside reverse transcriptase inhibitor. Pifeltro was approved alongside another Merck HIV treatment, Delstrigo, a once-per-day triple combination treatment. Merck anticipates both drugs being available to wholesalers within a month.

https://www.biospace.com/article/fda-approves-eight-novel-drugs-in-august-fd1a-/