Covid-19 Impact on Plasma Therapy in the Healthcare Industry

Covid-19 Impact on Plasma Therapy in the Healthcare Industry

  • Healthcare
  • May 15, 2020

Coronavirus is a large family of viruses known for diseases ranging from the common cold to even more serious diseases such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The virus has spread to almost all regions of the world, affecting both developed and developing countries which have heavily affected pharmaceutical and biotechnology companies. The epidemic spread rapidly across the globe within three months and was characterized by the VHO as a pandemic on March 11, 2020. According to the Worldometers.info statistics, as of 27th April 2020, there are 3,064,225 people are already affected and 211,537 patients are died due to the coronavirus. There are currently no approved specific antiviral agents targeting the new virus, while some drugs are still under investigation, including remdesivir and lopinavir / ritonavir. It is urgent to look for an alternative strategy to treat COVID-19, especially among severe patients, as an effective vaccine and specific antiviral medicines are not available till the date.

Plasma medications are produced from human blood plasma (plasma). Plasma can be obtained from administration of whole blood (recovered plasma) or apheresis procedures (plasma source). The source is plasma a wide range of medicinal therapies products used for treatment and the prevention of various treatment-causing injuries and diseases often associated with a protein deficiency state. Convalescent Plasma Therapy (CP), a classic adaptive immunotherapy, has been used in the prevention and treatment of many infectious diseases for over a century. In the past two decades, CP therapy has been successfully used in the treatment of the 2009 SARS, MERS and H1N1 pandemic with satisfactory efficacy and safety. In 2014, the World Health Organization (WHO) recommended the use of convalescent plasma therapy for the treatment of patients with antibody-rich plasma in those recovering from Ebola virus disease.

Numerous clinical trials are also being held to evaluate the safety and efficacy of convalescent plasma, and the FDA has also approved a number of individual emergencies (eINDs) for emergencies.

MECHANISM OF ACTION

Antibodies present in immune (i.e., "convalescent") plasma mediate their therapeutic action through various mechanisms. The antibody can bind to a particular pathogen (such as, a virus), thereby directly neutralizing its infectivity, while another antibody-mediated pathways such as complement activation, antibody-dependent cellular cytotoxicity, and / or phagocytosis may also contribute to its therapeutic effect. Non-neutralizing antibodies that bind to the pathogen - but they are does not interfere with its ability to replicate in in vitro systems - it can also contribute to prophylaxis and / or improve recovery. Most importantly, passive administration of antibodies offers the only short-term strategy for granting immediate immunity sensitive individuals. This is especially the case in the setting of a new, growing infectious disease such as SARSCoV-2 / COVID-19. While plasma products (such as, hyperimmune globulin, monoclonal antibodies) and / or fractionated vaccination can provide long-lasting therapeutic options, human anti-SARS-CoV-2 plasma is the only therapeutic strategy that is immediately available for use for the prevention and treatment of COVID-19.

REGULATIONS

COVID-19 convalescent plasma has not yet been approved by the FDA, to it is regulated as an exploratory product. As such, the COVID-19 administration convalescent plasma by a physician must be under investigation by a new drug application (IND) under traditional regulatory through IND, Extended Access IND, or newly announced administration of a new emergency drug (eIND) for one patient (42) U.S.C. 262(a)(3); 21 U.S.C. 355(i); 21 CFR 601.21; and 21 CFR 312.1).  The FDA is not doing collection of COVID-19 convalescent plasma or provides COVID-19 convalescent plasma. Healthcare professionals or acute care facilities would receive COVID-19 instead convalescent plasma from an FDA-registered blood establishment.

The below mentioned pathways are available for studying or administering the use of COVID-19 convalescent plasma:

1) Clinical Trials

Investigators who want to study the use of convalescent plasma in a clinical trial should submit requests to the FDA for investigative use in accordance with traditional IND regulations road (21 CFR part 312). CBER's Blood Research and Review Service are opted to engage with sponsors and quickly review such requests.

2) Expanded Access

The IND Extended Access application is an alternative to using COVID-19 convalescent plasma for patients with serious or immediate life-threatening conditions COVID-19 diseases that are ineligible or unable to participate randomized clinical trials (21 CFR 312.305). For patients with severe or the immediately life-threatening COVID-19 that is ineligible or unable to participate in randomized clinical trials, access to this research product may be available through the involvement of acute care facilities in expanded research access protocol under IND already in place.

3) Single Patient Emergency IND

The participation in clinical trials or an extended access program is the way to go patients gain access to convalescent plasma, for various reasons it may not be easily accessible to all patients in potential need. Therefore, given public health an emergency presented by the COVID-19 pandemic while clinical trials are ongoing implemented and extended access protocol is available, the FDA also allows access to COVID-19 convalescent plasma for use in patients with severe or immediately life-threatening COVID-19 infection through the process patient physician seeking one eIND patient for the individual patient below 21 CFR 312.310.  This procedure allows the use of an investigational drug for the drug treatment of an individual patient by a licensed physician upon FDA approval, if Applicable regulatory criteria were applied.

  1. To Obtain a Single Patient Emergency IND
    • To obtain a patient's individual eIND, the provider must determine that this is likely the risk to the person on the investigational drug is not greater than probable risk of disease or condition 21 CFR 312.310 (a).
  2. Patient Eligibility
    • To facilitate eIND requirements for the use of COVID-19 convalescent plasma for treatment patients, healthcare professionals seeking immediate medical attention may want to consider the problem eligibility criteria for the National Protocol for the Treatment of Extended Access were discussed in Section III.A. of these instructions. The criteria include:
      • Laboratory confirmed COVID-19
        1. Severe or immediately life-threatening COVID-19, for example,
        2. Severe disease is defined as one or more of the following:
          • oxygen saturation ≤ 93%,
          • partial pressure of arterial oxygen to inspiratory oxygen content <300
          • shortness of breath (dyspnea),
          • respiratory frequency ≥ 30/min,
      • lung infiltration> 50% within 24 to 48 hours
        1. A life threat is defined as one or more of the following:
          • septic shock,
          • respiratory failure,
          • multiple organ dysfunction or failure
      • Informed consent of patient or health care proxy.
  3. Collection of COVID-19 Convalescent Plasma
    • Donor Eligibility

COVID-19 convalescent plasma should only be collected from individuals eligible for donor eligibility (21 CFR 630.10 and 21 CFR 630.15). Please note the additional donor eligibility requirements for collection by plasmapheresis in 21 CFR 630,15 (b). Donation testing for relevant transfusion-transmitted infections must be performed (21 CFR 610,40) and the donation must be considered appropriate (21 CFR 630.30).

COVID-19 convalescent plasma is collected from the individuals they meet the following qualifications:

  • Evidence of COVID-19 documented by laboratory test:
    1. Diagnostic test (such as, nasopharyngeal swab) at the time of illness Or

    2. Positive serological test for SARS-CoV-2 antibodies afterwards recovery if previous diagnostic testing has not been performed COVID-19 is suspected.
  • Should meet one of the following:
    1. Complete resolution of symptoms at least 28 days before donation or
    2. Complete resolution of symptoms at least 14 days before donation

Negative results for COVID-19 of one or more nasopharyngeal swab specimens or molecular diagnostic test of blood

  • Male donors, or women who were not pregnant, or women to providers who have been tested since their last pregnancy and results interpreted as negative for HLA antibodies.

Once manufactured, COVID-19 convalescent plasma can be distributed for research use.

Blood establishments need not require an alternative procedure or exception under 21 CFR 640.120 (a) for COVID-19 reconvalescent plasma collection.

IMPACT ON DEMAND

Scientists are trying to use vaccines, medicines and other methods as a cure for the new coronavirus. With no confidence in the exact treatment in sight, doctors around the world are working on the treatment of centuries-old cure for infections: infusion of blood plasma that is immune to molecules can help survivors beat the infection. The demand of plasma therapy is increasing due to their potential use in the coronavirus treatment. The plasma therapy is the only therapy which shown positive results for the corona virus treatment. In addition to the US, China and Turkey, Spain, Italy, South Korea, the United Kingdom, there are some of the few countries that are also looking at plasma therapy to more easily address the worldwide coronavirus crisis. Even India joined the belt and started a trial for plasma therapy. In Delhi hospital has successfully cured COVID-19 patient using plasma therapy. The respiratory rate of the first patient was 30 which should be 15, and the oxygen saturation level was 85%, which should be 95%. After plasma therapy, the respiratory rate was 20 and the oxygen saturation level was 98%. This has been observed in all patients with increased respiratory rate and oxygen saturation level.

Government has already taken different initiatives to combat the corona virus. For instance,

  • The Indian Council of Medical Research (ICMR) now giving the climate to the state to conduct plasma therapy. Kerala is the first state in the state to get the climate to try this. In India, several states like Kerala, Gujarat and Punjab have already started using plasma therapy for patients with COVID-19.
  • The UK Government has approved a national clinical trial to evaluate plasma therapy for the treatment of Covid-19 patients.
  • Sewa International has created an online registry for a convalescent plasma therapy program that connects donors and recipients who wish to participate in COVID-19 treatment and has also established a helpline.

With the increasing demand and increasing sale of plasma therapy, are fueling the growth of plasma therapy market in the near future.

IMPACT ON SUPPLY

The development of hyperimmune will require the administration of plasma from many individuals who have fully recovered from COVID-19 and whose blood contains antibodies that can fight the new coronavirus. Once collected, "convalescent" plasma will then be transported to production facilities where it has undergone proprietary processing, including effective virus inactivation and removal processes, and then purified to product. The antibodies present in the blood can bind with the antigen. This is the limiting factor as the number recovered is much lower than the number of active cases in any geography. Also it depends upon an individual’s personal and ethical concerns to donate blood for plasma therapy.

Additionally, major problem with plasma therapy is the huge restrictions on the regulations that have led to disruption of product delivery. In spite of the difficulties, many patients already took part for the plasma donations. For instance,

  • The chief medical officer of The American Red Cross said, the American Red Cross has produced 200 units of convalescent plasma which has so far donated nearly by 150 donors. Additionally, he has mentioned, the goal is to send more than 1,000 units to hospitals, which would require 500-600 providers.
  • According to a recent survey, in Lucknow one Covid-19 recovered physician donated plasma to treat patients.

This can possibly be a roadblock to this revolutionary therapy. Though plasma therapy can prove to be a pioneering a part in treating a large number of patients but there is a number of limitations as discussed before. So a combination of treatments is already available for the corona virus treatment.

STRATEGIC DECISIONS OF MANUFACTURERS

Collaboration, agreements, strategic initiatives by market players such as CSL Behring, Takeda Pharmaceutical Company Limited, Biotest, Octapharma in the plasma therapy market will help them expand their market and expand their product portfolio. This, in turn, will help increase product demand among consumers, thus increasing future sales.

The plasma therapy manufacturers are taking much strategic decision to cope up with this current pandemic COVID-19. Global Plasma Leaders are collaborating to accelerate the development of potential COVID-19 hyperimmune therapy. Biotest, BPL, LFB and Octapharma have partnered to form an alliance formed by CSL Behring (ASKS: CSL / USOTC: CSLLI) and Takeda Pharmaceutical Company Limited (TSE: 4502 / NISE: TAK) to develop potential plasma therapy for COVID treatment-19. The alliance will begin immediately with the research development of a single, non-branded anti-SARS-CoV-2 polyclonal hyperimmune immunoglobulin drug with the potential to treat individuals with serious complications of COVID-19. The collaboration will leverage the cutting edge expertise and work that companies already do. Alliance experts will begin collaborating on key aspects such as plasma collections, clinical trial development, and manufacturing.

CSL Behring’s Executive Vice President and Head of Research and Development have mentioned that ‘Leaders lead during uncertainty. There is no question that we are all experiencing the impact of COVID-19’. He has also mentioned ‘This effort aims to accelerate a reliable, scalable and sustainable option for caregivers to treat patients suffering from the impact of COVID-19. In addition to pooling industry resources, we will also collaborate with government and academic efforts as a single alliance whenever we can, including important activities like clinical trials. This will make it more efficient in these hectic times for these stakeholders as well’.

President of Plasma-Derived Therapies Business Unit, Takeda have mentioned that ‘Unprecedented times call for bold moves’. He has also mentioned ‘We collectively agree that by collaborating and bringing industry resources together, we could accelerate bringing a potential therapy to market as well as increase the potential supply. We invite companies and institutions focusing on plasma to support or join our alliance’.

Emergency Bio Solutions, a medical biotechnology company, is one of the many players in the healthcare industry seeking to address the current global coronavirus epidemic. The company works on two different therapeutic approaches simultaneously. One is the use of human-derived plasma (a liquid that is the majority of blood) and one from horses. Human plasma-based treatment is ideal for hospitalized patients and for acute symptoms, and may provide some protection for at-risk people, including frontline health workers.

Takeda Pharmaceutical Company Limited and Alnilam Pharmaceuticals also entered into agreement to for development of new treatments for SARS-CoV-2 infection. Virus identified as the cause of the global COVID-19 outbreak the coronary virus treatment in the development. Takeda Pharmaceutical Company Limited also announced that it has begun development of TAK-888, an anti-SARS-CoV-2 polyclonal hyperimmune globulin (H-IG) which is designed for the treatment of high-risk individuals with COVID-19. Takeda Pharmaceutical Company Limited's H-IGs is a plasma derivative therapy that has previously been shown to be effective in treating acute viral respiratory infections.

Thus, companies operating in the plasma therapy manufacturing adopt a number of strategies, including collaborations, agreement, contracts, pipeline development, cooperation and market expansion to enhance their business. These strategic decisions by the companies are expected to provide significant opportunities for the market players operating in the plasma therapy market.

These studies have aroused hope. However, researchers warn that it is too early to think of plasma therapy as an effective treatment. For example, the sample sizes in Covid-19 plasma therapy trials are too small to draw definitive conclusions.

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