22 August 2018

HIV viral suppression rates nearly triples with ART use in US

A new study funded by the National Institutes of Health (NIH) has revealed that HIV viral suppression rates have nearly tripled over the past two decades with the use of antiretroviral therapy (ART).

The researchers surveyed a total of 31,930 adults receiving HIV care across eight clinical sites in the US. It was observed that viral suppression rates increased from 32% in 1997 to 86% in 2015.

Daily ART is intended to suppress the infection to undetectable levels. This treatment is considered lifesaving and prevents sexual transmission of the virus to others.

While early ART initiation and associated regimens led to improved overall viral suppression rates, disparities were found in select demographic groups, such as black people living with HIV.

The study also revealed that improvements in viral suppression plateaued between 2013 and 2015 among heterosexual individuals and people who inject drugs.

NIH National Institute of Allergy and Infectious Diseases experts said: “If HIV treatment as prevention is to help us reach the goal of ending the HIV epidemic in the US, it is critical to understand, address and bridge gaps in achieving viral suppression.”

Published in Annals of Internal Medicine, the study highlights such viral suppression gaps due to social and economic barriers.

NIAID researchers urged the public health community to use targeted interventions to better reach people experiencing low viral suppression rates.

Furthermore, the experts call for additional research to validate these findings and determine measures against the disparities. They also stress the need for new preventive strategies.

The experts added: “As the public health community strives to end the HIV epidemic in the US, targeted treatment interventions for populations with low levels of viral suppression, paired with tailored prevention packages, will be essential.”

20 August 2018

NICE advises against NHS use of Roche’s Perjeta for breast cancer 

The UK’s National Institute for Health and Care Excellence (NICE) has not recommended the routine use of Roche’s Perjeta (pertuzumab) in combination with trastuzumab by the National Health Service (NHS) for adjuvant treatment of human epidermal growth factor receptor 2 (HER2) positive breast cancer in its latest draft guidance.

NICE first rejected the pertuzumab combination in June, however, it decided to review its decision following changes to the cost of the drug combination.

The latest decision was based upon uncertainty about how clinical effective the pertuzumab combination is in preventing HER2 positive breast cancer from recurring after surgery. NICE’s committee also viewed the company’s predictions of overall survival to be over-estimated, making cost effective estimates too high.

Roche provided evidence from its Aphinity trial to support its drug. However, overall survival data from the study was immature and primary analysis showed no apparent difference between pertuzumab plus trastuzumab and chemotherapy plus trastuzumab. At year three the difference in invasive disease-free survival event rates between the two treatment arms was 0.9%; this increased slightly to 1.7% at year four.

There was also little evidence that pertuzumab and trastuzumab combination was more effective for node-positive or hormone receptor-negative HER2 positive breast cancer patients; these two groups are considered to be at the highest risk of recurrence following surgery.

Roche’s revised base case incremental cost-effectiveness ratios (ICERs) for pertuzumab combination compared to chemotherapy is £30,561. NICE’s evidence review group’s (ERG) ICER was £47,856.

NICE concluded that both prices relied on optimistic estimates for the relative effectiveness of the drug. It also noted that although a biosimilar for trastuzumab, which would reduce its cost, Roche’s combination therapy would still not be cost effective.

The regulator also considered if pertuzumab in combination with trastuzumab could be recommended for use within the Cancer Drugs Fund. However, it concluded it did not meet the criteria for inclusion and it was unlikely that further data collection through the fund would confirm more benefits than those already established by Roche’s studies.

The second and final drafts are expected in the next few months, with the final decision predicted to be published by December.

17 August 2018

FDA approves first generic of Mylan’s EpiPen

The US Food and Drug Administration (FDA) has approved the first generic version of the EpiPen and EpiPen Jr (epinephrine) auto-injector for severe allergic attacks, including life-threatening anaphylaxis.

The EpiPen was approved in 2007 and is marketed by Mylan. However, since then both the company and its product have been involved in a number of scandals. Notably the price of the EpiPen has increased from $57 in 2007 to approximately $600 in 2016 and in May, the FDA had to place Mylan’s EpiPen on its official shortages list as a result of manufacturing delays.

The newly approved generic epinephrine auto-injector will be available in 0.3mg and 0.15mg strengths and is marketed by Teva. This the company’s second attempt to get its generic approved by the FDA; it was rejected in 2016.

In a statement Teva said: “The approval of our generic version of EpiPen (epinephrine injection) auto-injector 0.3 mg and 0.15 mg in the US marks an important step forward in bringing patients additional prescription medications that have met the FDA’s rigorous standards.

“We’re applying our full resources to this important launch in the coming months and eager to begin supplying the market.”

FDA commissioner Scott Gottlieb said: “Today’s approval of the first generic version of the most-widely prescribed epinephrine auto-injector in the US is part of our longstanding commitment to advance access to lower cost, safe and effective generic alternatives once patents and other exclusivities no longer prevent approval.

“This approval means patients living with severe allergies who require constant access to life-saving epinephrine should have a lower-cost option, as well as another approved product to help protect against potential drug shortages.”

The epinephrine auto-injector is an example of what the FDA calls a combination product because it includes both a drug and the device for administering the drug. In order to obtain approval, combination products must meet the regulator’s standards of safety and efficacy.

Gottlieb said: “The path to developing generic drug-device combination products like this one is challenging. We’re especially committed to the development of generic copies of complex products. These products can be hard to copy, and therefore sometimes don’t face timely generic competition once patents and exclusivities are no longer a block to approval.”

The FDA previously approved other epinephrine auto-injectors under new drug applications, including Adrenaclick and Auvi-Q, as well as authorised generics marketed under the brand name made by the same manufacturer but with some alterations to labelling and packaging.

Mylan had an authorised generic approved in 2016, which retails at around $300. It is currently unclear how much Teva’s generic will cost.

14 August 2018

FDA approves direct-to-consumer contraceptive app Natural Cycles

The US Food and Drug Administration (FDA) has approved Sweden-based Natural Cycles, making it the first direct-to-consumer smartphone app used for digital contraception to be marketed in the country.

Natural Cycles is based upon the concept of fertility awareness and uses an algorithm to calculate the days in a month a woman is likely to be fertile based on daily body temperature and menstrual cycle information.

Consumers using the app must take their temperature daily using a basal body thermometer, which is accurate to two decimal points, and then input this information into the app. The system then informs the user if they need to use protection to prevent pregnancy that day. The app’s reliance on human input means there is a possibility of human failure or error.

The FDA’s decision was based clinical trials involving 15,570 participants who used the app for an average of eight months. Results from these studies showed the app was 93% effective with a so-called ‘perfect use’ failure rate of 1.8% and a ‘typical use’ failure rate of 6.5%.

The regulator did warn, however, that the app shouldn’t be used by women for whom pregnancy would present a major risk for the mother or foetus, or by women taking contraception or hormone treatments that inhibit ovulation.

FDA Center for Devices and Radiological Health assistant director for the health of women Terri Cornelison said: “Consumers are increasingly using digital health technologies to inform their everyday health decisions, and this new app can provide an effective method of contraception if it’s used carefully and correctly. But women should know that no form of contraception works perfectly, so an unplanned pregnancy could still result from correct usage of this device.”

Simultaneous with the marketing approval of Natural Cycles, the FDA created special controls to clarify the agency’s expectations in assuring the accuracy, reliability and effectiveness in preventing pregnancy using the app.

Natural Cycles received CE approval in early 2017, which means it is available in the European Union and general European Economic Area. In total it currently has approximately 900,000 registered users.

Natural Cycles chief technology officer and co-founder Elina Berglund said: “Based on the strength of our clinical data, Natural Cycles is the only app to be CE marked in Europe as a method of contraception, and we are delighted that the FDA has now granted the De Novo for Natural Cycles in the US.

“Our mission at Natural Cycles is to pioneer women’s health with research and passion, and we hope that by increasing the options available, more women will be able to find a method of contraceptive that works for them.”

The system has begun to face some criticism in recent months. Its certification is currently under review in Sweden after a hospital reported that 37 of the 668 women who sought an abortion between September and December 2017 were using the app as their sole method of birth control.

14 August 2018

Onpattro approved by FDA as first treatment for polyneuropathy

Alnylam Pharmaceuticals has obtained approval from the US Food and Drug Administration (FDA) for Onpattro (patisiran) to treat peripheral nerve disease (polyneuropathy) in adults with hereditary transthyretin-mediated amyloidosis (hATTR).

Onpattro is the first FDA-approved medicine for this indication. It also the first drug to secure authorisation under the new small interfering ribonucleic acid (siRNA) drugs class.

The siRNA mechanism involves silencing of a RNA portion related to pathogenesis of the disease.

Onpattro is designed to encase the siRNA into a lipid nanoparticle for direct delivery of the drug into the liver in order to change or stop the production of disease-causing protein called transthyretin (TTR).

By halting the TTR production, the medicine can help decrease the accumulation of amyloid deposits in peripheral nerves.

FDA Division of Neurology Products director Billy Dunn said: “There has been a long-standing need for a treatment for hereditary transthyretin-mediated amyloidosis polyneuropathy.

“This unique targeted therapy offers these patients an innovative treatment for their symptoms that directly affects the underlying basis of this disease.”

Onpattro’s efficacy was validated in a clinical trial called APOLLO performed in a total of 225 patients. The trial involved administration of the drug once every three weeks for 18 months.

Compared to the placebo groups, participants treated with Onpattro had better outcomes on polyneuropathy measures, such as muscle strength, sensation, reflexes and autonomic symptoms.

Onpattro also demonstrated favourable profile in assessments of walking, nutritional status and ability to perform daily activities.

The most common adverse reactions with Onpattro were found to be infusion-related, including flushing, back pain, nausea, abdominal pain, difficulty breathing and headache.

hATTR is a rare, debilitating genetic condition that results in build-up of abnormal amyloid protein in peripheral nerves and other organs, including heart. It affects around 50,000 people globally.

The FDA had previously granted Onpattro fast track, priority review, breakthrough therapy and orphan drug designations.

10 August 2018

Results from Chinese Changsheng’s rabies vaccine scandal unveiled

China’s State Council has reported initial results from its ongoing investigation into Changsheng Biotech, the country’s largest vaccine producer by revenue, following accusations from the Chinese National Drug Administration (CNDA) in July this year that the company had forged production and inspection records for 110,000 rabies vaccines.

According to state news agency Xinhua, the investigation has found that the company began falsifying production and inspection records as early as 2014. The outlet reported that Changsheg Biotech mixed some batches with expired solutions and then incorrectly recorded dates and batch numbers.

Criminal investigations into company chairperson Gao Junfang and eighteen executives arrested in connection with the vaccine scandal are currently ongoing. The State Council has also called for a full investigation into regulatory failings, plus the establishment of a long-term mechanism to ensure public safety moving forward.

Following the launch of an official investigation by President Xi, Changsheng Biotech was ordered to halt production and recall of all rabies vaccines, including those sold overseas. The company was also stripped of its licence to produce and sell the vaccine and fined $502,200.

Authorities in India have also announced they have banned the import of Changsheng Biotech’s vaccine and they are seeking to recall it from the market.

S Eswara Reddy, head of India’s drug regulator, said in an interview with local news agency: “The vaccine is being used in India, but we don’t have the exact details of the total number of units imported or where they have been distributed.

“Once we get the information, we will ask for a recall of the vaccine from market. But until then, there is a blanket ban on its import.”

Throughout the state investigation, the CNDA has remained in contact with the World Health Organisation (WHO) through the latter’s representation in China.

The WHO’s Representative for China, Gauden Galea said: “Regulatory oversight of vaccines is critically important. It is the government’s primary method of ensuring that the vaccines produced and used in China are safe, of good quality and effective. This incident shows that when regulatory oversight works well, potential risks can be averted.”

9 August 2018

Array BioPharma’s mCRC therapy gets breakthrough status

Array BioPharma has received breakthrough therapy designation from the US Food and Drug Administration (FDA) to use encorafenib (Braftovi) in combination with binimetinib (Mektovi) and cetuximab for the treatment of metastatic colorectal cancer (mCRC).

The indication covers patients with BRAFV600E-mutant mCRC as identified using an US Food and Drug Administration (FDA)-approved test, following no response to one or two previous lines of therapy.

BRAFV600E-mutant mCRC patients are at high mortality risk compared to people who have non-mutated mCRC. Currently the mutated type of mCRC lacks specifically approved treatments.

Braftovi is an oral small molecule inhibitor of BRAF kinase, while Mektovi inhibits MEK. The drugs target critical enzymes associated with the MAPK signalling pathway (RAS-RAF-MEK-ERK).

Array BioPharma chief medical officer Victor Sandor said: “As there are no regimens approved specifically for BRAFV600E-mutant mCRC, this designation provides us with the opportunity to work closely with the FDA to potentially accelerate our effort to bring an important treatment option to these patients in critical need.”

In the latest Phase III BEACON CRC clinical trial, the combination therapy demonstrated 62% overall survival rate at one year, eight months of median progression-free survival (mPFS) and 48% overall response rate (ORR).

The randomised, open-label, global trial is designed to assess the safety and efficacy of the triple combination therapy in 30 BRAFV600E-mutant mCRC patients whose disease progressed after one or two prior regimens.

Primary endpoint of the study, which is ongoing at more than 200 centres, is overall survival. The secondary endpoints include efficacy, PFS, ORR, duration of response, safety and tolerability.

Array holds exclusive rights to both Braftovi and Mektovi in the US and Canada.

Braftovi and Mektovi’s marketing authorisations are currently being reviewed by the European Medicines Agency, the Swiss Medicines Agency and the Australian Therapeutic Goods Administration. While the Pharmaceuticals and Medical Devices Agency in Japan is considering a manufacturing and marketing approval for the two drugs.

8 August 2018

MHRA outlines post-Brexit clinical trials regulation

The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has outlined how clinical trials regulation will function after the UK leaves the European Union (EU) in March next year.

A Brexit implementation period will commence between the UK and EU on 30 March 2019 and will lapse on 31 December 2020. During this period, the UK will not be a member state of the Union, but will have market access on the existing terms.

The EU is planning to implement a new Clinical Trials Regulation (CTR) in 2020, which would be applicable to the UK under the terms of the implementation period.

This CTR is intended to optimise application process and assessment procedure, simplify reporting, and offer only one portal for all EU clinical trials. The UK was also involved in devising the new rules.

In case the new legislation does not come into effect during the implementation period, the UK plans to retain alignment with parts of the CTR that are under its control.

However, after the implementation period, the UK will not be able to use a shared central IT portal and participation in the single assessment model, unless they come to an agreement with the EU.

A statement from MHRA read: “It is in the interest of patients and the life sciences industry internationally for the UK and EU to find a way to continue cooperation in the field of clinical trials, and for continued sharing of data, even if our precise relationship with the EU will by necessity change.

“No matter what the outcome of negotiations, the UK is committed to offering a competitive service for clinical trial assessment.”

The announcement on post-Brexit clinical trial regulation follows a recent confirmation by British Medical Association (BMA) that the UK is considering stockpiling of medical supplies in case of a no-deal Brexit.

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