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Clinical Study: Molnupiravir for the treatment of Feline Infectious Peritonitis [FIP]

Updated: Aug 16, 2023

1. PURPOSE The objective of this clinical trial is to assess the safety and effectiveness of Molnupiravir in treating naturally acquired feline infectious peritonitis (FIP). This report outlines our study methodology, real-world clinical data gathered during the trial, and our conclusion regarding the efficacy of Molnupiravir administered orally as a treatment for FIP. the efficacy of Molnupiravir via oral application for the treatment of feline infectious peritonitis (FIP).

2. INTRODUCTION

Since 2019, resistance to GS-441524 in the treatment of feline infectious peritonitis (FIP) has been increasingly observed, particularly among cats with neurological FIP. At present, drug resistance can be managed in two ways: by gradually increasing the dosage of GS-441524 until drug levels in body fluids surpass the resistance level, or by using an alternative antiviral drug that employs a different mechanism to combat FIPV, either alone or in conjunction with GS-441524. The former option has been the most frequently used and has proven successful in most cases. However, when GS-441524 resistance is total or extremely high, increasing the dosage can be prohibitively expensive and unpleasant for cats, necessitating the exploration of the latter option by researchers. Molnupiravir, a commercially available isopropylester prodrug of N4-hydroxycytidine, is one of the most promising alternatives or supplements to GS-441524.


Molnupiravir is effective in halting FIP virus replication by integrating into the RNA virus genome and inducing viral error catastrophe, resulting in the accumulation of mutations that render the FIP virus strains harmless to cats. The active component of Molnupiravir, beta-d-N4-hydroxycytidine, exists in two tautomeric forms, one mimicking cytidine and the other uridine. In the presence of beta-d-N4-hydroxycytidine, the viral RNA-dependent RNA polymerase interprets it as uridine instead of cytidine, leading to inconsistencies in transcription and numerous mutations in the viral genome, ultimately causing viral replication to cease.


3. METHODOLOGY

The clinical trial enrolled 34 cats with FIPV infection, ranging in age from 5 to 96 months. Among them, 21 cats (62%) were relapse cases and 12 cats were newly diagnosed with FIP. The cats were diagnosed with either non-effusive (dry) or effusive (wet) FIP, with 12 of them exhibiting ocular or neurological symptoms. No placebo control group was formed due to ethical considerations.


The dosage of Molnupiravir administered in the trial was 10mg/kg PO SID (oral once per day) for non-neuro/ocular FIP and 20mg/kg PO SID for ocular and neurological cases. The trial was divided into three phases of oral treatment, with each phase lasting 30 days. A full panel blood test was conducted for the cats at the end of each treatment phase.


Table 1 provides information on the participating cats, including their weight and the dosage of Molnupiravir administered. All cats underwent a pre-treatment blood test, and another blood test was conducted after 30 days of treatment to assess changes in key blood test markers. This report summarizes the results of the trial and presents the findings of the cats after completing the Molnupiravir treatment.

​Cat's Age

Cat's Weight (kg)

FIP Type

Status

Start of treatment

MT001

4

3.7

Neurological

Relapse

June 2022

MT002

2

3

Neurological

Relapse

June 2022

MT003

2

0.74

Wet

New FIP case

July 2022

MT004

9

2.5

Wet

New FIP case

July 2022

MT005

1

4

Ocular & Neurological

Relapse

July 2022

MT006

2

4.3

Wet

Not responding/slow progress to GS treatment

July 2022

MT007

3

3.8

Neurological

Not responding/slow progress to GS treatment

July 2022

MT008

4

1.6

Dry

New FIP case

July 2022

MT009

5

2.2

Wet

New FIP case

August 2022

MT010

11

5.8

Wet

Not responding/slow progress to GS treatment

August 2022

MT011

2

4.1

Neurological

Relapse

August 2022

MT012

10

1.8

Neurological

New FIP case

August 2022

MT013

2

3.8

Wet

New FIP case

August 2022

MT014

2

2.9

Dry

New FIP case

August 2022

MT015

3.5

2.9

Ocular & Neurological

Relapse

August 2022

MT016

5

5.8

Dry

Not responding/slow progress to GS treatment

August 2022

MT017

2

2.8

Wet

Not responding/slow progress to GS treatment

August 2022

MT018

2

3.4

Wet

Relapse

August 2022

MT019

2

4.1

Dry

Relapse

August 2022

MT020

1

4.9

Wet

New FIP Case

August 2022

MT021

2

4.2

Neurological

Relapse

August 2022

MT022

3

3.2

Wet

Relapse

August 2022

MT023

2.9

4.2

Wet

New FIP Case

August 2022

MT024

4

5.8

Wet

Not responding/slow progress to GS treatment

August 2022

MT025

1.5

3.4

Neurological

Not responding/slow progress to GS treatment

August 2022

MT026

1

1.4

Neurological

New FIP Case

August 2022

MT027

2

2

Neurological

Relapse

August 2022

MT028

2

1.4

Wet

Relapse

August 2022

MT029

4

0.5

Dry

New FIP case

August 2022

MT030

2

4.9

Dry

Not responding/slow progress to GS treatment

August 2022

MT031

2

5

Wet

Not responding/slow progress to GS treatment

September 2022

MT032

9

4

Dry

New FIP case

September 2022

MT033

9

5.4

Wet

New FIP case

September 2022

MT034

1

2.9

Neurological

New FIP case

September 2022

Tables 1-3: List of all cats participated in the Molnupiravir clinical trial.



4. RESULT & DISCUSSION

4.1 CATS EXITING THE TREATMENT

During the course of the clinical trial, 16 cat owners opted to discontinue the Molnupiravir treatment for their feline companions due to various reasons. Among them, 12 cat owners discontinued treatment after receiving feedback indicating that their cat's condition did not improve after starting Molnupiravir treatment (Figure A & B). Some cat owners lost their cats to FIP even while undergoing Molnupiravir treatment (Figure C). Two cat owners discontinued treatment within two weeks of starting due to the lack of observable improvement in their cats. One cat was advised to stop treatment due to kidney problems, and one cat owner chose to stop treatment without providing any reason.

4.2 TREATMENT OUTCOME

Of the initial 34 cats in the trial, 18 continued the Molnupiravir treatment. Unfortunately, three cats (MT001, MT007, and MT033) died or were euthanized within the first week of treatment due to severe disease and complications, and a fourth cat (MT005) died after four weeks of treatment from an unrelated eye disease. However, the remaining 14 cats completed the planned phases of treatment and remained healthy as of December 2022, with at least two phases of treatment.


The cats responded well to the treatment initially, with increased activity levels, but there was no marked improvement in their appetite, which may be due to the bitterness of Molnupiravir. Effusions in cats with effusive FIP disappeared within one to two weeks of treatment. Dyspneic cats (MT018, MT022) responded rapidly and were no longer apparent after five to seven days of treatment. Ocular disease symptoms in cats (MT015 and MT005) cleared in three to six days.

After about four weeks of treatment, all 14 cats appeared normal or near-normal according to their owners. The focus of treatment for at least six weeks was to monitor blood test parameters, including total white blood cells, total serum protein, serum globulin, serum albumin, and A:G ratio.


4.3 Favorable treatment response indicators

4.3.1 Weight

Table 2 shows the weight changes of the cats before and after treatment. Out of the 14 cats that completed the treatment, 11 cats (79%) showed weight gain, making it a simple long-term measure of treatment efficacy.

Weight (Pre-treatment)

Weight (Post-treatment)

​MT008

1.6

2.2

MT011

2

2.6

MT015

2.9

3.35

MT016

5.8

5.8

MT017

2.8

3.1

MT018

3.4

3.9

MT019

4.1

4.4

MT021

4.2

3.78

MT022

3.2

2.7

MT023

4.2

4.5

MT024

5.8

5.9

MT026

1.4

3

MT028

1.4

2.3

MT034

2.9

3

Table 2: ​The pre-treatment and post-treatment weight of cats that have completed the clinical trial for FIP treatment using Molnupiravir.


4.3.2 Serum protein

FIP cats often exhibit abnormal blood test results, such as high total serum protein concentration, high serum globulin, low serum albumin levels, and low A:G ratio. In this trial, 10 out of 14 cats that finished the treatment had the necessary blood tests. These cats' serum protein levels showed a gradual improvement and eventually reached normal levels after at least 2 treatment phases (60 days).

a/g ratio pre-treatment

a/g ratio post-treatment

Globulin pre-treatment

Globulin pre-treatment

MT017

0.4

0.4

53

50

MT018

0.4

0.63

58

39

MT022

​0.8

0.8

43

41

MT024

0.4

​0.5

76

69

MT016

​0.5

​0.5

50

48

MT019

​0.5

0.8

51

43

MT023

0.4

0.4

60

60

MT011

​0.8

​0.9

40

34

MT026

​0.5

0.6

54

44

MT034

0.4

0.5

72

55

Table 3 shows the globulin and albumin/globulin readings for both pre-treatment and post-treatment of the 10 cats who successfully completed the clinical study


4.3.3 Side effects

During the treatment, inappetence was observed in almost 43% of cats in the trial (6 out of 14). This effect was more pronounced when the content of the oral capsules was emptied and mixed with wet food for feeding. It is believed that the bitterness of Molnupiravir may have caused the cats to lose their appetite. Therefore, cat owners are advised to directly feed the whole capsules to help their cats regain their appetite during Molnupiravir treatment.


5. CONCLUSION

The clinical trial has established that Molnupiravir is a viable but inferior treatment option for some FIP cats with effusive (wet) and non-effusive (dry) forms of the disease. It may serve as an alternative treatment for FIP where GS-441524 has failed to inhibit FIPV replication. Molnupiravir can be used alone or in combination with GS-441524 for treating FIP. However, further research is needed to determine the safe dosage of Molnupiravir for commercial use in FIP treatment, and an in-depth study on its cytotoxicity is recommended.


Reference:

Pedersen, NC., and Jacque, N. (2021). Alternative treatments for cats with FIP and natural or acquired resistance to GS-441524. Pedersen, NC., Perron M., Bannasch, M., Montgomery, E., Murakami, E., Liepnieks, M., and Liu, H. (2019). Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis. Journal of Feline Medicine and Surgery. 2019;21(4):271-281.





Appendix

Figure A



Figure B



Figure C



Authorship: This study was conducted by the Research Team of Curefip.com with the aim of advancing FIP treatment. If you have any questions about this study, please visit our website, call us at +1 (646) 653-2654‬, or email us at curefipcustomercare@gmail.com.

Keywords: Feline infectious peritonitis, FIP, GS-441524, Molnupiravir, Remdesivir, FIP treatment, FIP cats.

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1 Comment


Ladislav Mihok
Ladislav Mihok
Feb 04, 2023

Who run this study? Wht I do not understand is why this study was not respecting absolutely fundamental fact, that molnupiravir is supposd to be admnistered every 12 hours (BID). It has different pharmacokinetics than GS441524. Also dosages you used for your "so-called" study are quite low or better said they are low for SID administration.

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