Pharma news – 5 July 2020

Indian Government is reviewing the use of Remdesivir for Covid-19 following reports of liver damage

The Union Health Ministry of India is currently reviewing the use of Remdesivir in the country. Multiple reports of liver damage in the Covid-19 patients treated with this drug have instigated this action. The side-effects of Remdesivir was one of the main topics of the meeting that was held by the ministry on 3 July 2020.

A senior official has stated that liver damage was reported in multiple public and private hospitals. This was attributed to the elevated levels of alkaline phosphatase, SGOT^[1] and SGPT^[2] that causes liver damage.

Remdesivir was developed by Gilead Sciences and used as an “investigational therapy” for Covid-19 patients in India. The use of Remdesivir is contraindicated to liver damage patients. But recent reports suggest a possible link between its use and liver damage.

Hetero and Cipla are the only drug firms that are allowed to sell Remdesivir in India. Hetero Labs has stated that it has not received any complaints of liver injury following the use of Remdesivir.

Alkaline phosphatase is an enzyme found in the bile ducts. It is used as a marker of liver health and elevated levels are correlated with liver diseases. SGOT and SGPT are also enzymes whose increased levels are associated with fatty liver and liver cancer.

The Health Ministry has recently discouraged the use of Remdesivir in patients with severe renal impairment, pregnant women and children under 12 years of age. Remdesivir is also not to be used in patients with signs of liver damage and lactating mothers.

Gilead had provided the safety profile of Remdesivir, and this clearly stated its ability to induce liver enzymes. Clinical studies revealed elevated transaminase levels and infusion-related reactions in hypersensitive patients. The drug firm strongly advises proper clinical and laboratory monitoring to detect the adverse effects at the earliest. The renal and hepatic functions must be monitored before initiating and daily during the treatment with Remdesivir. Serum chemistries and hematology must also be monitored daily. The therapy with Remdesivir is discontinued after the risk/benefit assessment for each patient.

Remdesivir is a broad-spectrum antiviral that was designed to treat Ebola. In April 2020, the effect of Remdesivir on 1063 advanced Covid-19 patients with lung involvement were tested. This study revealed the faster recovery of the patients treated with Remdesivir than the ones who received a placebo.

Preliminary results of this study showed that patients on Remdesivir therapy recovered in 11 days. The median time of recovery of the placebo group was 15 days. The patients in the Remdesivir group showed a 31% faster time to recovery than the placebo group. The mortality rate of the Remdesivir group was around 8% when compared to the 11.6 % mortality rate of the placebo group.

But a study conducted by the Chinese in April 2020 revealed that they did not find any significant clinical benefits on treatment with Remdesivir. Though not significant, the study showed that patients treated with Remdesivir recovered in 10 days or less. The adverse events were reported in 102 of the 155 remdesivir recipients, and this was around 66%.

However, the percentage of adverse effects was reduced to 64% in the placebo recipients as only 50 out of the 78 subjects reported them. Around 18 (12%) patients in the remdesivir group stopped the treatment early due to adverse effects. This was high when compared to the placebo group where only 4 patients (5%) stopped the treatment early.

Abbreviation: 1. Serum glutamic-oxaloacetic transaminase

• Serum glutamic pyruvic transaminase

2.DCGI approves AstraZeneca’s cardiac drug dapagliflozin

On 4 July 2020, AstraZeneca announced that Dapagliflozin tablets had received the DCGI’s^[1] approval for use in heart failure patients. Dapagliflozin tablets is used for heart failure patients with reduced ejection fraction.

Following this approval, the firm plans to launch 10mg film-coated tablets of Dapagliflozin in the country. It has also received the import and marketing permission from DCGI in Form CT-20.

Currently, dapagliflozin is being sold in India as a diabetic medicine. It is specifically used for lowering blood sugar in adults with type-2 diabetes.

The drug firm stated that dapagliflozin is the first in class inhibitor of SGLT-2^[2] that is approved for use in heart failure patients. It also significantly reduces the risk of hospitalization and cardiovascular death in heart failure patients with reduced ejection fraction.

Dapagliflozin has already been approved for use in cardiac patients in the USA after receiving the USFDA’s^[3] approval.

Heart failure is a dangerous condition that affects around 6.4 people globally. Around 8-10 million Indians are also affected by this disease. AstraZeneca claims that the launch of dapagliflozin will reduce the burden of these people and increase their life span. Currently, the market for cardiac drugs alone accounts for around Rs.2,000 plus crores.

Heart failure is a serious health condition in which the cardiac muscles are unable to pump properly. This inadequate pumping is not enough to meet the body’s demand for oxygen and blood. The patients usually experience rapid heartbeats and shortness of breath.

Abbreviation: 1. Drugs controller general of India

2. Sodium-glucose-co-transporter-2

3. United States Food and Drug Administration

3.Zydus Cadila’s indigenous vaccine gets DCGI’s approval for clinical trials

On 3 July 2020, Zydus Cadila announced that its plasma DNA vaccine, ZyCov-D received the DCGI-CDSCO’s^[1] approval for phase I/II (combined) human clinical trials. This vaccine was developed indigenously at the Vaccine Technology Centre in Ahmedabad.

Preclinical studies of this vaccine were conducted on mice, rats, guinea pigs, and rabbits. The drug firm claimed that the antibodies produced by this vaccine were able to neutralize the wild type virus completely. Toxicology studies also showed that this vaccine is safe for both intramuscular and intradermal routes of administration. About three times, the intended human dose was tested on rabbits, and this was found to safe and immunogenic.

The company plans to start the clinical trials in a week and complete the phase I/II trials by October-November. This will be followed by the phase III trials. The drug firm hopes to launch this vaccine in the market by early 2021.

The company is gearing up to test the clinical GMP^[2] batches of the vaccine candidate in around 1000 people. The trial will be carried out at multiple sites across India.

Zydus Cadila expects the demand for this vaccine to increase and intends to increase the production of ZyCov-D. This drug firm also holds the prestige of being the first company to indigenously develop a vaccine for swine flu in India in 2010.

Abbreviation: 1. Drugs Controller General of India-Central Drugs Standard Control Organization

2.Good Manufacturing Practices

References:

^[1] – Remdesivir use for covid– The Print – 3 July 2020

^[2] – Astrazeneca’s Dapagliflozin– Outlook India – 4 July 2020

^[3] – Zydus Cadila to begin human trials of COVID-19– Business Today – 3 July 2020