Asia-Pacific Roundup: Singapore’s HSA finds benefits outweigh risks for JAK inhibitors

The benefits of using Janus kinase (JAK) inhibitors for approved inflammatory indications outweigh the associated risks, according to a safety review by Singapore’s Health Sciences Authority (HSA).
 
JAK inhibitors such as Pfizer’s Xeljanz (tofacitinb) and AbbVie’s Rinvoq (upadacitinib) can improve outcomes in patients with a range of inflammatory diseases including rheumatoid arthritis and atopic dermatitis. However, regulators around the world have raised concerns about the safety of the class of molecules, with the US Food and Drug Administration (FDA) applying a boxed warning and its European counterpart recently recommending steps to minimize the risk of serious side effects.
 
HSA conducted its review in response to the findings of ORAL Surveillance, a post-authorization safety study that linked Xeljanz to a higher risk of major adverse cardiovascular events and cancers than Humira (adalimumab), a TNF inhibitor marketed by AbbVie. The same safety study triggered the European review of JAK inhibitors.
 
Working with its Product Vigilance Advisory Committee, HSA concluded that “the benefit-risk profile of JAK inhibitors for the treatment of inflammatory conditions remains positive for their approved indications.” The use of JAK inhibitors is already limited to second line or later therapy in Singapore.
 
HSA is advising healthcare professionals to take certain precautions. Noting that “other JAK inhibitors used in the treatment of inflammatory conditions may have similar risks as observed with [Xeljanz] in the ORAL Surveillance study,” HSA is asking healthcare professionals to consider the benefits and risks before prescribing the drugs and to monitor patients for potential risks during treatment.
 
HSA singled out the elderly, current or past smokers, and people with other cardiovascular, malignancy or thromboembolic risk factors as populations that are important to monitor. In Europe, the safety committee recommended against using JAK inhibitors in much the same population unless no suitable treatment alternatives are available.
 
To date, HSA has received two adverse event reports of breast cancer and death associated with the use of Xeljanz, although the presence of an “intercurrent medical condition” and confounding factors mean the events may be unrelated to the JAK inhibitor. Similarly, a patient on Rinvoq had a stroke but they went on to restart treatment with the same JAK inhibitor without incident.
 
HSA Notice
 
CDSCO committee calls for local trial of  lupus drug
 
The Central Drugs Standard Control Organisation’s (CDSCO) analgesic and rheumatology committee has advised AstraZeneca to study its systemic lupus erythematosus drug Saphnelo (anifrolumab) in the Indian population before seeking approval.
 
Saphnelo—a first-in-class type I interferon receptor antibody—is approved in the US, EU, UK, Japan, Canada and Australia. It was the first treatment for systemic lupus erythematosus approved in the US in more than a decade.
 
Having secured approvals in other markets, AstraZeneca presented a proposal to import and market the product for adults “with moderate to severe systemic lupus erythematosus who are receiving standard therapy with local clinical trial waiver” in India.
 
While noting that AstraZeneca presented “the results of various clinical trials conducted in other countries,” the committee zeroed in on the fact “there is no study data available in [the] Indian population.”
 
At the same meeting, the committee also considered the results of a Phase 4 study presented by Johnson & Johnson, a request by Amgen to run a clinical trial and a protocol amendment by Pfizer.
 
SEC Recommendations
 
Malaysia’s MDA stops conditional approvals of COVID tests as search for new CEO begins
 
Malaysia’s Medical Device Authority (MDA) has stopped all conditional approval and special access for COVID-19 test kits. Going forward, test developers will need to follow the standard registration process, as set out in the Medical Device Act 2012, to place such tests on the Malaysian market.
 
As the pool of available COVID-19 diagnostics has grown, and demand for testing has fallen, regulatory agencies around the world have considered how to transition from the emergency pathways needed in the pandemic to boost supply to the standard pathways that are viable now the situation has stabilized. MDA set out its response late last week.
 
The Malaysian device authority said, “conditional approval and special access for COVID-19 test kits have been halted and future placement of COVID-19 test kits on the market shall be subjected to their registration under section 5 of the Medical Device Act 2012 (Act 737).” Developers of COVID-19 test kits that have completed evaluation at the testing facilities and passed the set performance criteria should use the Medical Device Centralized Online Application System, MeDC@St, to register their devices.
 
MDA shared details of the new approach days before publishing a job listing for a new chief executive. The authority is seeking applications from Malaysian citizens with at least 15 years of experience in the medical device sector and 10 years of experience at senior management level.
 
MDA Notice, Job Listing
 
TGA extends substitution of angina medicine after shortage forecast to continue until June
 
Australia’s Therapeutic Goods Administration (TGA) has extended the Serious Scarcity Substitution Instrument (SSSI) for isosorbide mononitrate until 30 June 2023 because the shortage of the angina pectoris medicine is now forecast to last longer.
 
TGA published the SSSI in September in response to shortages of Imdur Durules and Monodur Durules isosorbide mononitrate 120 mg modified release tablets. At the time, the agency expected the shortages to continue until 19 December. However, TGA has now learnt that the products are forecast to remain in short supply until 31 May 2023.
 
By extending the SSSI, the regulator has empowered pharmacists to substitute two doses of the Clinect product, 60 mg and 120 mg, without prior approval from the prescriber until the end of June. TGA will cancel the SSSI early if the shortage is resolved sooner than currently expected.
 
TGA Notice
 
Malaysia revises device law to require filings for license renewal 90 days before expiry
 
Malaysia’s MDA has amended the Medical Device Act 2012 to require companies to apply to renew their establishment licenses at least 90 days before their expiry date.
 
As MDA explained in a notice to disclose the change, applications made beyond the license expiry date will not be accepted and the holder of the expired license will need to file a new application. MDA will not refund license renewal fees paid by companies that file their applications after the 90-day deadline.
 
When first published, the act stated “a licensee may apply for renewal of its establishment license to the Authority not later than one year before the expiry date of the establishment license.”
 
MDA Notice (Malaysian)
 
Other news:
 
Singapore’s HSA has published its mean response times for new and major variation applications for the six months up to 30 September. The data cover new and generic drug applications, plus major variation applications. HSA Notice